MM

CLINICAL PRACTICE GUIDELINES
on Newer and Emerging

Addictive Disorders in India
Published by Indian Psychiatric Society, India
Editors
Debasish Basu | P.K. Dalal | Y.P.S. Balhara
Indian Psychiatric Society

Specialty Section on Substance Use Disorders
CLINICAL PRACTICE GUIDELINES
on Newer and Emerging
Addictive Disorders in India

2016
Editors
Debasish Basu
P.K. Dalal
Y.P.S. Balhara
Published by
INDIA
Clinical Practice Guidelines on
Newer and Emerging Addictive Disorders in India
Editors:
Debasish Basu
P.K. Dalal
Y.P.S. Balhara
First Edition: January, 2016
Price : Rs.500/-
Rs.100/- for IPS Members
Editorial Office:
Dr. Debasish Basu
Professor of Psychiatry, Drug De-addiction & Treatment Centre,
Department of Psychiatry,
Postgraduate Institute of Medical Education & Research,
Chandigarh-160012, India.
Email: db_sm2002@yahoo.com
Prepared by:
Speciality Section on Substance Use Disorders
For copies:
Dr. Gautam Saha
Chair, IPS Publication Committee
Printed at:
Repro Digital Pvt. Ltd.
192B S.P. Mukherjee Road, Kolkata 700026
An Official Publication of Indian Psychiatric Society
© All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in
any form or by any means, electronic, mechanical, photocopying, digital, recording or
otherwise, without the prior permission of the publishers.
ii
INDIAN PSYCHIATRIC SOCIETY
OFFICE BEARERS AND EXECUTIVE COUNCIL MEMBERS (2015-16)
President : Dr. Vidyadhar Watve
Vice-President : Dr. G. Prasad Rao
General Secretary : Dr. N. N. Raju
Hon. Treasurer : Dr. Vinay Kumar
Hon. Editor : Dr. T.S.S. Rao
EXECUTIVE COUNCIL
Immediate Past President : Dr. T. V. Asokan
Immediate Past Secretary : Dr. Asim Kumar Mallick
Executive Council Members (Direct)

Dr. Kishor Gujar
Dr. O P Singh
Dr. K K Mishra
Dr. Om Prakash
Dr. Mrugesh Vaishnav
Dr. Arabinda Brahma
Dr. (Surg Captain) Sunil Goyal
Zonal Representatives
Central Zone : Dr. Sarvesh Chandra, Dr. Jai Prakash Narayan
East Zone : Dr. C L Narayan, Dr. Hiranya Goswami
West Zone : Dr. D M Dhavle, Dr. Mukesh Jagiwala
North Zone : Dr. R K Solanki, Dr. Chander Mohan
South Zone : Dr. A J John, Dr. Abhay Matkar

SPECIALTY SECTION ON SUBSTANCE USE DISORDERS
Chair : P. K. Dalal
Convener : Debasish Basu
Members :
Atul Ambekar | Y.P.S. Balhara | Kaustav Chakraborty
Prabhat Chand | Anju Dhawan | Shubh Mohan Singh | B. N. Subodh
IPS PUBLICATION COMMITTEE

Chair : Gautam Saha
Convener : Sandeep Shah
iii
Clinical Practice Guidelines on
Newer and Emerging Addictive Disorders in India
SPECIALTY SECTION ON SUBSTANCE USE DISORDERS
2016
AUTHORS
Atul Ambekar
Additional Professor
National Drug Dependence Treatment Centre
Department of Psychiatry
All India Institute of Medical Sciences (AIIMS), New Delhi 110029
atul.ambekar@gmail.com
Yatan Pal Singh Balhara

Assistant Professor
All India Institute of Medical Sciences (AIIMS), New Delhi 110029
ypsbalhara@gmail.com
Aniruddha Basu
Senior Resident and DM Addiction Psychiatry Candidate
Drug De-addiction & Treatment Centre
Postgraduate Institute of Medical Education & Research (PGIMER)
Chandigarh 160012
draniruddhabasu@gmail.com
Debasish Basu
Professor of Psychiatry
Chandigarh 160012
db_sm2002@yahoo.com
Kaustav Chakraborty
Assistant Professor
College of Medicine and J.N.M. Hospital, Kalyani
West Bengal University of Health Sciences, West Bengal
drkaustav2003@yahoo.co.in
iv
Prabhat Chand
Additional Professor of Psychiatry
Centre for Addiction Medicine
National Institute of Mental Health and Neuro Sciences (NIMHANS),
Bangalore 560029
prabhatkumarchand@gmail.com
P.K. Dalal
Professor and Head
King George's Medical University
Lucknow 226003
docpkdalal@gmail.com
Abhishek Ghosh
Chandigarh 160012
ghoshabhishek12@gmail.com
Shrigopal Goyal
Assistant Professor
Shiv Kishan Midaram Dammani Government Institute of Mental Health,
Allied & Neuro Sciences (DIMHANS),
Department of Psychiatry & De-addiction, PBM Hospital
S.P. Medical College and Associated Groups Hospitals, Bikaner (Rajasthan)
shrigopalgoyal@gmail.com
Arun Kandasamy
Assistant Professor of Psychiatry
National Institute of Mental Health and Neuro Sciences (NIMHANS)
Bangalore 560029
arunnimhans05@gmail.com
Ananya Mahapatra
Senior Resident
All India Institute of Medical Sciences (AIIMS)
New Delhi 110029
nnyaa09@gmail.com
v
Surendra K. Mattoo
Professor Psychiatry
Chandigarh 160012
skmattoo@ymail.com
Pratima Murthy
Professor of Psychiatry
Bangalore 560029
pratimamurthy@gmail.com
Subodh B.N.
Associate Professor of Psychiatry
Chandigarh 160012
drsubodhbn2002@gmail.com
Rajarshi Neogi
Assistant Professor
Institute of Psychiatry
Institute of Postgraduate Medical Education & Research and
SSKM Hospital
Kolkata 700020
neogi123@gmail.com
Sathya Prakash
Senior Resident
New Delhi 110029
dr.sathyaprakashtbts@gmail.com
Siddharth Sarkar
Assistant Professor
New Delhi 110029
sidsarkar22@gmail.com
vi
Lekhansh Shukla
Bangalore 560029
drlekhansh@gmail.com
Shubh Mohan Singh

Associate Professor
Chandigarh 160012
shubhmohan@gmail.com
vii
PREFACE
It gives me great pleasure to write the Preface of the book
“Clinical Practice Guidelines on Newer and Emerging Addictive
Disorders in India”, published by the Indian Psychiatric Society.
In 2014, the IPS Specialty Section on Substance Use Disorders
had brought out an entirely new set of comprehensive Clinical
Practice Guidelines (CPGs) on the assessment and management
of common substance use disorders. This is a rich and updated
source of knowledge and skills, comprehensive in its width as well as depth of
coverage. However, a need was felt to produce an evidence-based synopsis of the
previous exhaustive reference book, targeted directly for the practitioners and
students, for an easy checking and implementation. This brief “Synopsis” was
published in 2015.
Moving on from there, this current set of CPGs focuses on four newer and emerging
areas of direct concern to the Indian scenario: New Psychoactive Substances,
emerging drugs in the Indian context, a more in-depth focus on dual disorders, and
last but not the least, the new group of addictive disorders called “Behavioural
Addictions.” All these are important for Indian psychiatrists as well as medical
specialists likely to come across addictive disorders more often than ever. Despite
the lack of rigorous evidence in some of these areas, the eminent authors of this book
have done their best by highlighting the emergent gravity of the problems, collating
the updated evidence to the extent possible, and making recommendations for
practice concordant with the current state of knowledge and expertise.
I congratulate the IPS Specialty Section on Substance Use Disorders on this
ambitious task. I also thank the Publication Committee of IPS for publishing this
useful book with great care. I wish that IPS should come up with more such volumes
on various important psychiatric topics in future, setting a healthy and helpful
tradition.
Dr. Vidyadhar Watve
President, Indian Psychiatric Society
January, 2016
viii
FOREWORD
It is a matter of pleasure to know that Indian Psychiatric Society is
bringing out yet another useful book on “Clinical Practice
Guidelines on Newer and Emerging Addictive Disorders in India”.
Drug addiction is an important psychosocial problem from time
immemorial and is found amongst all cultures and civilizations
across the world throughout history. Drug addiction causes
immense human distress and unfortunately there is no part of the
world that is free from it. Millions of people all over the world are
leading very miserable and pathetic lives. The drug abuse is a complex phenomenon
with involvement of social, cultural, biological, geographical, historical and economic
aspects.
All of us know that there are innumerable varieties of drugs which are abused but most
commonly used include alcohol, nicotine, cannabis, opioids, inhalants, and
benzodiazepines. Earlier, The IPS Specialty Section on Substance Use Disorders brought
out Clinical Practice Guidelines (CPGs) on the assessment and management of these
common substance use disorders in two volumes. The Comprehensive handbook was
released at the Annual National Conference of the IPS (ANCIPS) in 2014, and the
Synopsis of the same was released at ANCIPS 2015.
Of late there have been several developments in this area. Newer psychoactive
substances have been emerging on the Indian scene, some of them old but used more
often in India lately (like cocaine), and others are so new that they are not even
mentioned in the legal statutory schedules of controlled drugs. Patients with co-
occurring psychiatric disorders and drug addictions are seen and recognized more
frequently. Finally, a newly designated group of behavioural problems, termed as
'behavioural addictions', is making the mark, most notable of them being Pathological
Gambling and Pathological Internet Use (or Internet addiction), but there are many
others although they are more controversial at present. It is difficult to treat these
conditions, firstly because these are newer entities and challenges in the Indian scenario
and secondly because strong evidence base is often lacking.
Given this important but difficult development, the IPS Specialty Section on Substance
Use Disorders have again risen to the challenge and have produced a CPG book, written
by experts in the field, to bring these issues to the forefront.
Indian Psychiatric Society is happy to involve in bringing out the latest developments in
the field of addictions and I am sure the handbook will be very useful to experienced
clinicians, young postgraduates and serious researchers. I thank Dr. P.K. Dalal, Dr.
Debasish Basu, Dr. Gautam Saha and Dr. Sandeep Shah in addition to all authors for
completing such a daunting task. Of course such a dream would not have been reality but
for the support extended by Dr. Vidyadhar Watve and the EC members.
Long live IPS!
Dr. N.N. Raju
ix
FROM THE DESK OF IPS PUBLICATION COMMITTEE
Dear Member,
The landscape of medical education has
changed rapidly in recent years and will
continue to do so into the future. In addition,
the composition of our continuing medical
education will continue to change, with
increasing numbers and shares of the
population coming from communities of color. In this publication we use
experimental clinical projection techniques to capture the impact of these changes
on the size and ethnic composition of medical education to the members of each
state, each zone, and nationally the Indian Psychiatric Society as a whole.
A number of individuals were instrumental in the preparation of this publication.
First and foremost among them were authors who played critical roles at several
steps along the way to publication. Special thanks to Dr. P.K. Dalal and Dr. Debasish
Basu who designed and produced the layout and graphics; who edited the text and
helped proof the data; who built the interactive tool providing readers with
customizable data and graphics for our Society; and we also like to design in the web
environment for the online version of the publication.
We would also like to thank those individuals who gave of their time and expertise in
serving on the technicalities over the past few months. Finally, our thanks go to all
the senior members for their generous support of the preparation, publication, and
dissemination of this edition.
IPS Publication Committee prepares the white paper that formed the foundation of
the methodology review component of this work. In short, we hope the future is a
brighter one than what we experience here – for all members.
All the authors earn our sincere gratitude for their efforts on this publication.
We thank our President Dr. Vidyadhar Watve, Vice-President Dr. G. Prasad Rao,
Hony General Secretary Dr. N.N. Raju, Hony Treasurer Dr. Vinay Kumar, Hony
Editor Dr. T.S.S. Rao, and grateful to all Council Members for helping and
cooperating us to run the Publication Committee at ease.
Long live I.P.S.
Dr. Gautam Saha Dr. Sandeep Shah

Chairperson, Publication Committee Convener, Publication Committee
Indian Psychiatric Society Indian Psychiatric Society
x
INDIAN PSYCHIATRIC SOCIETY –
SPECIALTY SECTION ON SUBSTANCE USE DISORDERS (IPS-SS-SUD)
CLINICAL PRACTICE GUIDELINES ON

NEWER AND EMERGING ADDICTIVE DISORDERS IN INDIA
CONTENTS
Title Author Page No.
Front Matter i-x
Section A: General Overview
Clinical practice guidelines on newer Debasish Basu, PK Dalal, 5
and emerging addictive disorders: YPS Balhara
Overview of IPS guidelines 2016
Addiction – a hydra-headed problem Pratima Murthy 15
Section B: Newer and Emerging Substances
New Psychoactive Substances: Debasish Basu, 27
An overview, with focus on synthetic Abhishek Ghosh
cannabinoids and cathinones
Cocaine Subodh BN, 51
Aniruddha Basu
Amphetamine-type Stimulants Atul Ambekar, 87
Shrigopal Goyal
“Club Drugs” Kaustav Chakraborty, 121
Rajarshi Neogi
Section C: Behavioural Addictions
Gambling disorder Abhishek Ghosh, Debasish Basu, 181
PK Dalal
Pathological Internet Use Prabhat Chand, Arun Kandasamy, 221
(“Internet Addiction”) Pratima Murthy
Other putative behavioural Arun Kandasamy, 237
addictions Lekhansh Shukla
Section D: Dual Diagnosis
Dual Diagnosis: Psychotic disorders YPS Balhara, Sathya Prakash, 263
Ananya Mahapatra, Siddharth Sarkar
Dual Diagnosis: Shubhmohan Singh, SK Mattoo 309
Non-psychotic disorders
xi
SECTION A :
GENERAL OVERVIEW
CLINICAL PRACTICE GUIDELINES ON
NEWER AND EMERGING ADDICTIVE DISORDERS:
OVERVIEW OF IPS GUIDELINES 2016
Debasish Basu
P.K. Dalal
Y.P.S. Balhara
On behalf of
2016
Overview
BACKGROUND
Following the reconstitution of the Specialty Section on Substance Use Disorders of the
Indian Psychiatric Society (IPS-SS-SUD) in 2011, the members of the Specialty Section
strongly felt the need for formulating a set of evidence-based, methodologically sound
and updated Clinical Practice Guidelines (CPG) for the assessment and management of
the common substance use disorders in India. Following a long and rigorous process of
development, a book was finally released at the Inauguration Ceremony of the 66th
Annual National Conference of the Indian Psychiatric Society (ANCIPS) held in Pune in
January 2014. It was an official publication of the IPS, brought out by IPS-SS-SUD,
named “Clinical Practice Guidelines for the Assessment and Management of Substance
Use Disorders” (referred hereafter as the “CPG-SUD book”).1 The following areas were
covered in the CPG-SUD book of 2014: assessment of substance use disorders in
general; alcohol use disorders; opioid use disorders; cannabis use disorders; sedative-
hypnotic use disorders; tobacco use disorders; inhalant use disorders; and dual
diagnosis. It was a comprehensive book running into 531 pages, with a masterly
compendium of references and updated knowledge crystallized into practical
recommendations.
Later, however, it was felt that there was a need for a more concise, practice-oriented,
easy-to-follow “Synopsis” of the comprehensive CPG-SUD book as well, which would
be a set of compact, precise, yet evidence- and expertise-based guidelines. Again an
official publication of the IPS, the “Synopsis” book was released at the Inauguration
Ceremony of the 67th Annual National Conference of the Indian Psychiatric Society
(ANCIPS) held in Hyderabad in January 2015.2 Easy-to-carry in a pocketbook sized
format, and easy-to-use with clear tables, panels, boxes and algorithms, it was a perfect
supplementary companion of the comprehensive CPG-SUD book. It synthesized all the
practice-relevant information necessary for the assessment and management of
common substance use disorders and dual diagnosis. In order to maintain
comparability and consistency with the CPG-SUD book, it contained the same chapters
in the same order: assessment of substance use disorders in general; alcohol use
disorders; opioid use disorders; cannabis use disorders; sedative-hypnotic use
disorders; tobacco use disorders; inhalant use disorders; and dual diagnosis.
Since the publication of the CPG-SUD book in 2014 and the Synopsis book in 2015,
both have been well received by clinical practitioners, researchers, academicians, and
psychiatric students, i.e., by all the target groups these two books were meant for. They
have provided the clinicians with updated and evidence-based guidelines for
assessment and management of substance use disorders, and others with a
comprehensive compendium of updated knowledge that can be a rich resource for
academic purposes of teaching, learning, and research.
© Indian Psychiatric Society 2016 5

Newer and Emerging Addictions in India
Need for the current volume of CPG

As mentioned above, the first two books were devoted to CPGs on common substance
use disorders in India because it was the felt need of the Indian psychiatrists at that
moment. However, the scenario of addictive disorders is never a static one. It witnesses
continual kaleidoscopic changes, with newer substances, newer patterns, and indeed,
newer 'addictions' emerging all the time.
Four broad changes have been noted in the landscape of addictive disorders in India of
late. These are:
(a) Emergence of a heterogeneous group of various substances clubbed under the term
“New Psychoactive Substances (NPS)”, which evade the existing regulatory legal
framework but nonetheless, can be harmful;
(b) Emergence of long-known but so far less used substances in India in an emergent
manner (such as cocaine and amphetamine-type stimulants), often in the context of
rave parties or similar gatherings (the so-called “club drugs”);
(c) Appearance of novel, if somewhat controversial, patterns of maladaptive
behavioural excess involving particular behaviours (gambling, use of technology
like computer and Internet, eating, sexual activities, etc.), which do NOT primarily
involve use of psychoactive substances as such (known as “behavioural
addictions”); and finally,
(d) Enhanced probability of clinically encountering various combinations of substance
use disorders with non-substance psychiatric disorders (known as dual diagnosis or
dual disorders).
After the first-level basic coverage was completed in the first two books, it was felt
appropriate now to move on to the next stage, or phase, of CPG development, focusing
on these newer or emerging areas. This need was clearly foreseen in the Overview
Chapter of the CPG-SUD book in 2014: “CPGs on stimulants and hallucinogens have
not been incorporated, nor on 'club drugs' or 'new psychoactive substances', because
we had to prioritize the content according to the currently existing predominant
patterns of substance use in India. However, the scenario of substance use is always a
fluid one, and newer drugs, including cocaine and other stimulants, and the so-called
'club or rave' drugs, have made entry into select circles of substance users in India. A
future revised edition of this book may therefore add new CPGs on these SUDs as
well.”3
This is the purpose of the current volume, which may be seen as the blossoming of the
plant, the seed of which was sown in the 2014 volume!
The Process of Development of these CPGs
This CPG has followed the same process of development as the original CPG-SUD
6 © Indian Psychiatric Society 2016

Overview
book. The CPG-SUD book was the culmination of intensive year-long efforts of a group
of dedicated psychiatrists working in the field of substance use disorders in various
reputed academic medical institutes of India. The development, refinement and
finalization of these Clinical Practice Guidelines (CPGs) was the result of an arduous,
long-drawn and rigorous process following a pre-defined iterative strategy involving
progressively widening circles of peer review.
The pre-defined strategy for the process of development, refinement and finalization of
these CPGs has been mentioned in details in the “Overview” chapter of the CPG-SUD
book.3 The process is recapitulated briefly here.
Although all the members of the IPS-SS-SUD were variably involved in the process of
development and/or refinement of the each of the CPGs, one senior author (a Faculty
Member of a teaching medical institute with special interest and expertise in addictive
disorders) was designated as the “Lead Author” for each of these CPGs. They co-opted
additional contributors, not below the rank of a Senior Resident in psychiatry and
working in the area of addictive disorders. These authors developed their respective
CPG assigned to them.
In the process of development, we were guided by: (a) an extensive review of the
relevant literature, including Indian data wherever available in published and
retrievable form; (b) pre-existing recent guidelines in this area; (c) an awareness of the
local needs and priorities whenever applicable (e.g., the need to focus on smokeless
tobacco use in India); (d) need to balance the rigor and extensiveness of data coverage
with the pragmatic considerations of condensing and filtering the data for practical use
by clinicians; (e) need to rate the category of evidence and the strength of
recommendations as per internationally accepted norms;4 and (f) the Appraisal of
Guidelines for Research and Evaluation II (AGREE-II) instrument.5 These (strength of
evidence and recommendations, and AGREE-II instrument, with degree of compliance
displayed by most of these CPGs) are mentioned in the Appendix, and have been
followed throughout all the CPGs.
The CPGs thus developed were finalized through an iterative process of progressively
widening circles of peer review. Ethical issues and potential conflicts of interest were
also taken care of, as mentioned explicitly in the “Overview” chapter of the CPG-SUD
book.3
The Organization of the Book Chapters and the CPGs
Following this overview chapter, the next chapter is called “Addiction – a hydra headed
problem.” Written by an eminent addiction psychiatrist who has been working in the
area for many decades, it is really an experiential overview that sets the tone for the rest
of the book, focusing on the essential roles and challenges of the psychiatrist in
addiction psychiatry, especially in view of newer addictions and dual diagnosis.

The next Section of the book starts with an overview of the “New Psychoactive
Substances (NPS)” and their relevance for the emerging Indian scenario. This chapter
defines and classifies all categories of NPS but focuses on only those not covered in later
chapters. It especially covers synthetic cannabinoids and synthetic cathinones
(especially mephedrone, colloquially known as “meow meow”, which has already
emerged as a major threat in several parts of India).
The following three chapters are on cocaine, amphetamine-type stimulants (ATS), and
“club drugs” respectively. Together with the NPS overview, these chapters cover the (a)
and (b) of the changes noted in the Indian substance use horizon as mentioned above. It
is to be noted that these are not watertight mutually exclusive subjects. Cocaine and
some older ATS drugs like amphetamines are not NPS because they are regulated under
the schedules of the International Conventions and the Indian Narcotic Drug and
Psychotropic Substances Act 1985. Club drugs comprise a loosely defined
heterogeneous group of substances that can include cocaine and ATS. Thus, these
chapters have been artificially carved out more out of practical necessities than for any
basic underlying principles, except for the fact that these do cover the newer and
emerging substances of use and their patterns of use in India.
The next Section focuses on the newer and again somewhat loosely defined entity
called “Behavioural Addictions”. The first chapter in this Section, Gambling Disorder, is
also the only one to have made the final mark by being included in the “Substance Use
and Related addictive Disorders” section of the Diagnostic and Statistical Manual, 5th
edition (DSM-5) of the American Psychiatric Association. Pathological Internet Use,
also popularly known as “Internet addiction” could not make the final mark in DSM-5 as
a definitive disorder but one sub-portion of it (Internet Gaming Disorder) has been
relegated to the last section of DSM-5 as “conditions that need further study”. This has
been covered in the next chapter in this book keeping in view its rising importance both
in the popular media as well in the clinical and scientific circles. The last chapter in this
section covers all those so-called behavioural addictions which are still best categorized
as “putative” but nevertheless has an emerging body of research backup and can be a
clinically encountered problem.
The final Section is on assessment and management of dual diagnosis disorders.
Although covered in a general manner in the previous two CPG books,1,2 the need was
felt to deliberate upon this area in a more comprehensive manner because of their
increasing prominence in clinical setups. One chapter in this Section focuses on dual
diagnosis psychotic disorders while the other focuses on non-psychotic disorders.
Each chapter begins with a clinically useful “Executive Summary” that summarizes the
key recommendations and issues. Individual “Key Recommendations” are mentioned
at the end of each major subsection of the chapters, occasionally also marking areas of
present uncertainty. These summary points and recommendations come with the
grading of evidence and strength as mentioned in the Appendix of this chapter.

Overview
While not always possible or feasible, we have attempted to maintain a degree of

uniformity and consistency in the structure and format across all the chapters. Each
chapter is subdivided into several sections and sub-sections, which are numbered
hierarchically in a numerical-point scheme (1, 1.1, 1.1.1, etc.) so that navigation along
these subsections becomes easier and more meaningful for the reader. Scope and
methodology including search strategies have been mentioned. Special attention has
been paid to locate and highlight Indian studies and the applicability of the
recommendations to the Indian situation. Certain special populations or situations have
also been mentioned at the end of each chapter if available. Finally, along with
pharmacological therapies, a conscious emphasis has been placed on non-
pharmacological (psychosocial, cognitive and behavioural) interventions as well, to the
extent possible.
Potential Readership, Utility, Scope, and Limitations of these CPGs
These are Clinical Practice Guidelines; hence the primary target audience for these
CPGs is the practicing clinicians (especially psychiatrists but also non-psychiatric
medical doctors and even non-medical professionals working in the area of addictive
disorders). They should benefit from the Executive Summary and Key
Recommendations to be applied in their clinical practice. Whoever is further interested
can look up the relevant literature cited in the text as and when needed.
The secondary, but very important, audiences include, among others, medical teachers,
postgraduate students, and researchers. These CPGs provide a comprehensive
compendium of updated knowledge that can be a rich resource for academic purposes
of teaching, learning, and research. Finally, these might be of benefit to medical
institutes and to policy makers to inform healthcare related decisions in the area of
SUDs (e.g., the decision to fund and implement opioid substitution treatment
programmes in an institute or in a state or even national basis).
Like any CPG, along with their potential utility as outlined above, their scope and
limitations need to be kept in mind so as to avoid their misuse, and encourage their
correct use. Ever since the Institute of Medicine in 1990 defined CPGs as “systematically
developed statements to assist practitioner and patient in decisions about appropriate
health care in specific clinical circumstances”,6 the benefits, lack of benefits, and
potential harms have been hotly debated, and the debate continues till date. Without
going into details of these 'pros and cons' debates, our humble submission to the
readers and potential users of this book and its individual chapters is: please remember
that CPGs are “guidelines”, not mandates or obligatory standards required by law or by
an institute, though mandates may later be derived from them as a policy matter. CPGs
are meant to inform, assist and “guide” the clinician, not ask them to sacrifice their
autonomy of clinical judgment, nor to be oblivious of the individual patient's clinical
situation and psychosocial context. Neither do we claim that these CPGs cover

everything under the sun related to SUDs. We had to necessarily prioritize the content
and coverage of the areas, and, in this process, some sections might have been missed.
Another important limitation has to be kept in mind while interpreting the
recommendations made in this book. Many of these subject areas are new and
emerging, and rigorous 'double-blind randomized controlled trials' – the cornerstone of
evidence-based medicine – are often absent, rare, or of small size or poor quality.
Hence, the evidence ratings in many areas are of a low grade. Accordingly, the
recommendations are necessarily of a “D” or “S” category, and many times no specific
recommendations can be made at this level of knowledge and experience. Perhaps the
situation may change by the time a later edition of this book is published. This statement
does not reduce the value of this book but rather puts in proper perspective.
With this statement of the scope, declarations and limitations as a 'disclaimer', we
would like to end by reiterating that if used for the correct purpose and in the correct
manner, we hope that these CPGs should prove useful to both their primary as well as
secondary readerships.
REFERENCES
1. Basu D, Dalal PK (eds). Clinical Practice Guidelines for the Assessment and
Management of Substance Use Disorders. Delhi: Indian Psychiatric Society, 2014.
2. Dalal PK, Basu D (eds). Synopsis of the Clinical Practice Guidelines on Substance Use
Disorders. Delhi: Indian Psychiatric Society, 2015.
3. Basu D, Dalal PK. Clinical practice guidelines for the assessment and management of
substance use disorders: overview of IPS guidelines 2014. In, Basu D, Dalal PK (eds).
Clinical Practice Guidelines for the Assessment and Management of Substance Use
Disorders. Delhi: Indian Psychiatric Society; 2014, pp. 1-12.
4. Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing
guidelines. BMJ 1999; 318: 593–596.
5. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE Next
Steps Consortium. AGREE II: advancing guideline development, reporting and
evaluation in health care. CMAJ 2010; 182: E839-E842.
6. Field MJ, Lohr KN (eds). Clinical Practice Guidelines: Directions of a new Program.
Committee to advise the Public Health Service on Clinical Practice Guidelines, Institute
of Medicine. Washington DC: National Academy Press; 1990.

Overview
APPENDICES
Appendix 1. AGREE-II instrument, and compliance of CPGs developed by IPS-SS-SUD
AGREE II Item CPGs of IPS-SS-SUD 2016

Overall objective(s) of the guideline To develop evidence-based and experience-
based clinical assessment and management
options for selected substance use disorders,
behavioural addictions, and dual diagnosis.
The population (patients, public, etc.) to Patients with substance use disorders,
whom the guideline is meant to apply behavioural addictions, and dual diagnoses.
The target users of the guideline The primary target users of these guidelines
are practicing clinicians (especially
psychiatrists but also non-psychiatric medical
doctors and even non-medical professionals
working in the area of addictions).
The secondary, but very important, target
users include medical teachers, postgraduate
students, researchers and policy makers at
various levels.
Systematic methods used to search for Existing guidelines, systematic reviews, RCTs
evidence and other clinical trials, and various
observational studies were identified from
PubMed, EMBASE, Google Scholar and other
database searches, from the Cochrane
Database as well as from guidelines and
identification by experts in the field.
The methods for formulating the This guideline is based on the synthesis and
recommendations interpretation of available evidence obtained
from studies across the world, especially in light
of the Indian context, rating them on strength of
evidence and combining this strength with the
perceived importance and relevance in the
Indian context to finally arrive at specific key
recommendations as well as identifying current
areas of uncertainty where applicable.
The health benefits, side effects, and risks Yes
have been considered in formulating
the recommendations
There is an explicit link between the Yes. Further, it has been clearly pointed out
recommendations and the supporting where no specific recommendations can be
evidence made at this time because of lack of supporting
evidence of acceptable quality.

AGREE II Item CPGs of IPS-SS-SUD 2016

A procedure for updating the guideline is No, not at this stage. However, these CPGs
provided may be updated every 5-7 years, or
specifically added or modified
recommendations may be made available
online if major changes in evidence are
witnessed in specific areas.
The recommendations are specific and Yes. However, these are not algorithmic or
unambiguous “cook-book recipe” recommendations to be
followed blindly. Rather, major principles are
recommended, which have to be applied
along with clinical judgment in individual
circumstances.
The different options for management of the Yes, to the extent possible.
condition or health issue are clearly
presented.
Key recommendations are easily identifiable. Yes, wherever available.
The guideline provides advice and/or tools on Yes, usually but not in very instance.
how the recommendations can be put into
practice.
The guideline describes facilitators and This issue has not been specifically addressed
barriers to its application. in these CPGs.
The potential resource implications of This issue has not been specifically addressed
applying the recommendations have been in these CPGs.
considered.
C o m p e t i n g i n t e r e s t s o f g u i d e l i n e All authors declared “No conflicts of interest.”
development group members have been
recorded and addressed.
Appendix 2. Categories of Evidence and Strength of Recommendations

(followed throughout these CPGs).4
Categories of evidence
Ia : evidence from meta-analysis of randomised controlled trials
Ib : evidence from at least one randomised controlled trial
IIa : evidence from at least one controlled study without randomisation
IIb : evidence from at least one other type of quasi-experimental study
III : evidence from non-experimental descriptive studies, such as comparative
studies, correlation studies and case-control studies
Overview
IV : evidence from expert committee reports or opinions and/or clinical experience of

respected authorities
Strength of recommendations
A : directly based on category I evidence
B : directly based on category II evidence or extrapolated recommendation from
category I evidence
C : directly based on category III evidence or extrapolated recommendation from
category I or II evidence
D : directly based on category IV evidence or extrapolated recommendation from
category I, II or III evidence
S : Standard of care

ADDICTION – A HYDRA HEADED PROBLEM
HERCULEAN CHALLENGES FOR THE PSYCHIATRIST
Pratima Murthy
On behalf of
2016
Addiction
1. INTRODUCTION
The American Society of Addiction Medicine in 20111 redefined addiction as a chronic
brain disorder. An editorial close on the heels of this proclamation in the Lancet2,
cautioned that the over-medicalisation of addiction could have its downsides.
Whatever the position, there is general agreement that being addicted is really like
being in a maze, with confusing signals emitted both from within the individual (from
biological predisposition and temperament) as well as from external factors (family,
society and other aspects of the environment)3. An understanding of vulnerability, effect
of substances on the body and mind, effective medical and psychosocial interventions,
family support and follow-up support are all important for restitution and recovery.
Who can better balance the science and art of addiction management than the
psychiatrist!
2. ADDICTION - A COMPLEX HYDRA HEADED PROBLEM
During residency training in the 1980's, my tryst with addiction was predominantly
with alcohol dependence. We saw persons with alcohol dependence and treated them
with disulfiram and psycho-social interventions. We saw nicotine dependence, but did
precious little except giving half-hearted advice to quit smoking. A lot has changed in
the three subsequent decades. In fact, change has been the only constant in the area of
addiction and its management.
2.1 What has changed?
1. The nature of chemical addictions has changed- since the first case report of heroin
use in India in the 1970's, the problem of opiate use has been escalating
throughout the country, and both illicit and pharmaceutical opioids dominate the
landscape4. We are increasingly encountering sedative/hypnotic dependence,
particularly benzodiazepine dependence in clinical practice5. Many young people
are brought to treatment settings with inhalant misuse and dependence. Cannabis
use and cannabis related problems continue to be present. Clinics are starting to
see cocaine, LSD and stimulant abuse. The use of ketamine has been reported
nearly two decades ago6 and continues to be prevalent. Instances of diversion of
opioid substitution medications like buprenorphine, newer opioid drugs including
tramadol abuse7 and news reports of novel psychoactive substances like
mephedrone (colloquially known as “meow meow”)8 are increasing.
2. We have learnt that licit drugs like nicotine and alcohol are associated with greater
public health problems in comparison to illicit drugs whose supply is more
strongly controlled. There is now a national tobacco control programme and
tobacco cessation clinics and treatments are becoming more readily available in
hospitals and practice settings.
3. In the last two decades, the face of addiction has changed. The scenario has moved
beyond chemical addictions to various kinds of behavioural addictions. These

include gambling, gaming, Internet addiction, food addiction, sex addiction,

shopping addiction and other behavioural addictions9,10.
4. Gender and substance use is another area that is garnering greater attention, with
more women being brought for the treatment of addiction, narrowing gender
ratios, all underscoring the need to develop gender-sensitive treatment
approaches11.
5. We are recognising the need to look at addiction on a developmental continuum,
from the foetal effects of maternal substance use12, to the growing problem of
substance use among the elderly13.
6. Cases of substance use are often complex to manage - with both physical and
psychiatric co-morbidities. Dual diagnosis poses its own unique evaluation and
management challenges.
7. The successful management of addiction includes not just the management of
craving and relapse, but the effective management of co-morbidities.
8. Therapeutic nihilism is still very prevalent and many psychiatrists are hesitant, if
not loath to treat persons with addiction. A large part of this nihilism stems from a
lack of skills as to how to approach such persons and lack of a collaborative
approach with the patient.
9. Addiction is recognised as a chronic, relapsing condition, with outcome rates
similar to other chronic diseases14 and planned follow-up and aftercare yields
better treatment retention and outcome15.
10. A range of pharmacotherapeutic and psychotherapeutic options have become
available or used more often in the last two decades. Nicotine replacement
strategies, bupropion, varenicline and re-emerging interest in cytisine for tobacco
dependence; acamprosate, naltrexone, topiramate, baclofen, N-acetyl cysteine for
alcohol and other addictions; buprenorphine and methadone (old drugs that have
become popular in the armamentarium of harm reduction approaches), drugs used
for co-morbidities (including atomoxetine, anti-depressants, mood stabilisers, anti-
convulsants). Interactions between prescribed drugs and abused substances pose
fresh challenges to the treating psychiatrist. Psychotherapeutic options including
motivation enhancement, cognitive behavioural interventions, mindfulness
interventions, relapse prevention strategies, among others. It is generally accepted
that a combination of psychosocial and pharmacological interventions work better
than either alone.
3. FOCUSING ON TWO OF THE NEWER CHALLENGES
Two broad areas in addiction that has captured both professional and public attention
are the behavioural addictions and dual disorders. Both these have become areas of
specialisation within addiction and deserve special attention.

Addiction
3.1 Behavioural Addictions

Behavioural addictions resemble chemical addictions in many ways. What underlies
these is a compulsion to repeatedly perform a rewarding behaviour – sometimes called
a natural reward – despite negative consequences to the person's physical, mental,
social, and/or financial well-being. A variety of behavioural disorders, both old and new
are now described16. These include, among a host of conditions, gambling, food,
shopping, sex and technology addictions. The main challenge with behavioural
addictions is that they are an extension of normal behaviours and behaviours that are
normally reinforcing or rewarding. Sometimes the description of behavioural
addictions is carried to the extreme, a case of nosologomania, not uncommon to
psychiatry17, with every known behaviour (listening to music, praying, working) being
described as a potential addiction.
Following the first published report of addictive use of the Internet appeared in the mid-
1990s18, there has been a plethora of published literature on the subject. Just as with the
definition of case-ness in psychiatry, determining case-ness in such addictions poses a
problem. This is because behavioural addictions involve 'normal drives', and are only
considered addictions when the behaviours reach a certain degree of excess and harm.
Griffith19 succinctly summarises that the difference between and excessive healthy
enthusiasm and an addiction is that 'health enthusiasms add to life whereas addictions
take away from it. There are several schools of thought on whether behavioural
addictions belong with other addictions, are part of a impulsive-compulsive spectrum
disorder, or cross-cutting disorders that overlap with anxiety states, depression,
obsessive compulsive disorders, attention-deficit hyperactivity disorders and
personality disorder. There are, on the other hand, critics who raise the doubt of
whether these are at all illnesses, or impulsive irresponsibility, or socio-cultural
phenomena that should not be medicalised. Whatever the view-point, and whether or
not these are disorders in their own right or epiphenomena of underlying psychiatric
morbidity, it is nevertheless a clinical reality that we see patients who have serious
problems with behaviours such as gambling, shopping, sex and the use of technology,
causing much distress to others or themselves. DSM V recognises pathological
gambling and gaming disorder as established behavioural addictions. The current focus
has been to understand the factors that predispose such behaviours - genetic risk,
temperament, co-occurring psychiatric illness, impaired decision making abilities, and
so on.
There are several issues with behavioural addictions. Can the same criteria for chemical
addiction be applied to behavioural addictions? Some of the supportive evidence
comes from imaging studies that found similar brain imaging changes in alcohol users,
cocaine users and persons with obesity20. Griffith19 suggests that apart from salience,
tolerance, withdrawal symptoms and tendency to relapse, other hallmarks of a
behavioural addiction include the mood modification properties of the behaviour and

the conflict associated with such behaviour.

Some researchers suggest a common diathesis across behaviour addictions. A high co-
occurrence of compulsive sexual behaviour and gambling is a case in point21. Is then the
wide spectrum of behaviour addictions a case of “diffr'nt strokes for diffr'nt folks”
(sufferers, clinicians, epidemiologists and nosologists), or should we be take a more
sensible unitary path? A unitary hypothesis is further supported by the fact that patients
treated with dopaminergic agents for idiopathic Parkinsonism commonly developed
new onset pathological gambling and sexual compulsivity22.
Engagement, treatment and follow-up retention are some important challenges in
behavioural addictions.
3.2 Co-morbid Disorders
It would not be an exaggeration to say that addiction rarely occurs alone. There are
invariably accompanying conditions which include psychiatric diagnosis, personality
or temperament related issues, as well as medical co-morbidities.
In the narrow sense, dual disorders refer to the co-existence of addiction with a
psychiatric disorder. There are multiple relationships between the use of substances and
psychiatric symptomatology. Acute or chronic use of substances can produce
symptomatology indistinguishable from independent psychiatric disorders; substance
use can precipitate or worsen pre-existing psychiatric illnesses; substance use can be a
method of coping with psychiatric symptoms; the two conditions may occur
independent of each other; the emotional and social disturbances that occur in these
two conditions may be indistinguishable from one another23. Most importantly, an
underlying psychiatric illness can undermine interventions for substance use or
behavioural addictions.
Prolonged heavy use of drugs and/or alcohol can result in an array of serious health
conditions. When one adopts a much broader view of co-morbidity, a plethora of
physical conditions including infections as well as non-communicable diseases fall in
the rubric of co-morbidity.
There have been a few studies from India that have highlighted both psychiatric and
medical co-morbidity among substance users24.
In respect of co-morbid disorders, there are several issues that merit attention and
discussion. These include the exploration of shared vulnerability between substance
use and other psychiatric disorders, the development of appropriate diagnostic
approaches to co-occurring disorders and the development/ adaptation of treatments for
such conditions.
The neurobiological interface between mental disorders and substance use has been
gathering tremendous interest in the last couple of decades with a focus on shared
molecular biology, neurotransmitter systems and neural circuits25.

Addiction
Addressing SUDs from a life stage perspective with assessment and treatment
approaches incorporating co-occurring disorders are necessary to successfully impact
overall health26.
Treatment of dual diagnosis [co-occurrence of a substance use disorder (SUD) in
patients with mental illness] poses several challenges for mental health professionals27.
In spite of the high association between substance use and psychiatric disorders, there is
a surprising paucity of studies related to treatment and outcome.
4. CHALLENGES BEFORE THE PSYCHIATRIST
With the definition of addiction broadening beyond the use of chemical substances to a
range of behaviours that also possess similar characteristics, research is moving from a
system that classifies addiction according to clinical symptoms to one more rooted in a
mechanistic understanding of the disease, with a greater role for genetic imaging and
cognitive science28.
Newer drug and behavioural addictions: Improving professional knowledge and
competencies
Knowledge Competencies Training and Resource Mobilisation

Kinds of newer drugs, Clinical evaluation and Training of psychiatrists and other
effects of use, symptomatic management health professionals in the
intoxication, overdose, of the various clinical identification, assessment,
dependence and presentations engagement, treatment, crisis
withdrawal management, relapse prevention
Relevant Investigations Use of appropriate Support for trained human resource

investigations for detection and facilities for management
in body fluids, assessment including relevant
of systemic complications pharmacotherapy
Pharmacology and Symptomatic and specific Funding support for research on

interactions with other management of underlying newer drugs of abuse and
substances of abuse as conditions including long- behavioural addiction including
well as medications term management epidemiology, clinical
presentations, treatment, course and
outcome
Available Management of Policy and advocacy to address and
pharmacotherapy and underlying vulnerability minimise the individual and public
psychosocial health impact from the use and
management for newer addiction to newer drugs of abuse
drug addictions as well as behavioural addictions

Knowledge Competencies Training and Resource Mobilisation

Complications Co-management of co-
associated with morbidities and liaison
psychiatric and other with other specialties
medical co-morbidities
and their management
Behavioural addictions- Effective recognition and
similarities and management of
divergence from behavioural addictions
chemical addictions,
their co-morbidities and
management
Vulnerability including Management in different
genetic risk, clinical and community
temperament, etc. populations including
children and adolescents
and in special settings like
prison
However, while treatment options have expanded quite a bit in the last few decades, the
generally established set of psychosocial and pharmacological approaches used for
substance addiction form the mainstay of treatment even for the newer addictions. The
current day psychiatrist is best advised to be well informed of the changing patterns of
addictions, special populations requiring specialised care, behavioural and other newer
addictions, co-morbidities and their management and the social and legal ramifications
of the newer addictions. Thus contemporary psychiatry will have to constantly adapt
itself to understanding the dynamic and hydra-headed problem of addiction in order to
provide effective management.
REFERENCES
1. American Society of Addiction Medicine. Definition of Addiction. 2011.
http://www.asam.org/pdf/Advocacy/PressReleases/20110815_DefofAddiction.PR.pdf
2. The Lancet. Addiction: a complex disorder. Editorial. The Lancet, 2011; 378:742.
3. Murthy P. Addiction: Is there light at the end of the tunnel? Indian Psychiatric Society
mid-term CME publication, September 2011.
4. Larance B, Ambekar A, Azim T, Murthy P, Panda S, Degenhardt L, Mathers B. The
availability, diversion and injection of pharmaceutical opioids in South Asia. Drug
Alcohol Rev 2011; 30 (3): 246-254.
5. Chand PK, Murthy P. Megadose lorazepam dependence. Addiction 2003; 98
(11):1635-1636.
6. Singh S, Murthy P. Ketamine Dependence. Indian J Psychiatry 2001; 43(2):175-177.

Addiction
7. Chand PK, Jayaram N, Murthy P. Iatrogenic tramadol addiction. Indian J Med Sci 2015,
in press.
8. Yahoo News. Meow Meow and the walking dead: India's newest drug. November 12,
2015. http://news.yahoo.com/meow-meow-walking-dead-indias-080000387.html
9. Rosenberg KP and Feder LC. An introduction to behavioural addictions. In, Behavioural
Addictions. First Edition. Criteria, Evidence and Treatment. Rosenberg KP and Feder LC
(Eds). London: Academic Press, 2014.
10. Indian Council for Medical Research. Behavioural addiction in the community: an
exploration. Sharma MK, Benegal V, Girish N, Thennarasu K.
http://www.icmr.nic.in/final/Behavioural%20addiction%20in%20the%20community
.pdf
11. Murthy P (Principal author and scientific editor). Women and Drug Use in India:
Substance, Women and High-Risk Assessment Study. United Nations Office on Drugs
and Crime, Ministry of Social Justice and Empowerment, United Nations Development
Fund for Women 2008.
12. Nayak R , Murthy P, Girimaji S, Navaneetham J. Foetal alcohol spectrum disorders. J
Trop Paediatr 2012; 58 (1): 19-24.
13. Nadkarni A, Murthy P , Crome IB, Rao R. Alcohol use and alcohol-use disorders
among older adults in India: a literature review, Aging Ment Health 2013; 17 (8):979-
91.
14. McLellan AT, O'Brien C P, Lewis D, Kleber HD. Drug addiction as a chronic medical
illness: implications for treatment, insurance and evaluation. JAMA 2000; 284:
1689–1695.
15. Murthy P, Chand PK, Harish MG, Thennarasu K, Prathima S, Karappuchamy,
Janakiramiah N. Outcome of alcohol dependence: The role of continued care. Indian J
Community Med 2009; 34 (2): 148-151.
16. Rosenberg KP and Feder LC (Eds). Behavioural addiction. Criteria, evidence and
treatment. London: Academic Press, 2014.
17. Van Praag HM. Impact of classification on psychiatry. Dialogues Clin Neurosci 1999;
3(1):141-151.
18. Young K. Psychology of computer use: Addictive use of the Internet: A case that breaks
the stereotype. Psychol Rep 1996; 79: 899-902.
19. Griffith M. A 'components' model of addiction within a biopsychosocial framework. J
Subst Use 2005; 10: 191-197.
20. Wang GJ, Volkow ND, Thanos PK, Fowler JS. Similarity between obesity and drug
addiction as assessed by neurofunctional imaging: a concept review. J Addict Dis 2004;
23: 39-53.
21. Grant JE, Steinberg MA. Compulsive sexual behaviour and pathological gambling. Sex
Addiction Compulsivity 2005; 12: 235-244.
22. Bostwick JM, Hecksel KA, Stevens SR, Bower JH, Ahlskog JE. Frequency of new-onset

compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson

Disease. Mayo Clinic Proc 2009; 84:310-316.
23. DHHS Publication No. (SMA) 95-3061. Printed 1994. Assessment and Treatment of
Patients with Coexisting Mental Illness and Alcohol and Other Drug Abuse Treatment
Improvement Protocol (TIP) Series 9.http://adaiclearinghouse.org/downloads/TIP-9-
Assessment-and-Treatment-of-Patients-with-Coexisting-Mental-Illness-and-Alcohol-
and-Other-Drug-Abuse-78.pdf
24. Murthy P, Manjunatha N, Subodh B N, Chand PK, Benegal V. Substance use and
addiction research in India. Indian J Psychiatry 52(1), Supplement 2010.
25. Brady KT, Sinha R. Co-occurring mental and substance use disorders: the
neurobiological effects of chronic stress. Am J Psychiatry 2005; 162: 1483-1493.
26. Schulte MT, Hser Y-I. Substance use and associated health conditions throughout the
lifespan. Public Health Reviews. 2014.
27. Murthy P, Chand P. Treatment of dual diagnosis disorders. Curr Opin Psychiatry 2012;
25 (3): 194-200.
28. Holmes D. Addiction: four big questions. Nature 2015; 522: s63.

SECTION B :
NEWER AND EMERGING SUBSTANCES

NEW PSYCHOACTIVE SUBSTANCES:
AN OVERVIEW, WITH FOCUS ON
SYNTHETIC CANNABINOIDS AND CATHINONES
Debasish Basu
Abhishek Ghosh
On behalf of
2016
New Psychoactive Substances
CONTENTS
Executive Summary
1. Introduction
2. Scope and methodology of the guideline
3. Profile of NPS users
4. Assessment of suspected cases of NPS intoxication
4.1. Clinical assessment
4.2. Laboratory assessment
5. Management of synthetic cannabinoids/cathinone intoxication or toxicity
5.1. Treatment setting
5.2. Management of sympathomimetic toxidrome
5.3. Management of psychiatric symptoms
5.4. Management of withdrawal symptoms
6. Long term management for NPS use disorders
7. Conclusion

EXECUTIVE SUMMARY
Introduction - New psychoactive substances (NPS) refer to a large and ever-increasing
rubric of chemicals with pharmacological properties and clinical effects resembling a
known illicit substance. During 2014, 500 psychoactive substances were officially
notified for the first time in the European Union (EU). Since then, the EU's early warning
system has updated the list on a number of occasions. NPS are classified broadly into
five categories: ketamine, piperazine, synthetic cathinones, synthetic cannabinoids,
and plant based substances. These drugs might cause significant health hazards and also
have the potential to cause addiction. Although there is no general population based
survey on NPS, data from the emergency departments, poison research centers, and
Internet surveys indicate an increasing trend of NPS use.
Methodology - This chapter focuses on two NPS, i.e. Synthetic cannabinoids and
Synthetic cathinones. There are no published meta-analysis, reviews, open-label trials,
randomized double-blind trials, and placebo-controlled trials with regard to the
management of NPS intoxication. Hence, the evidence of this guideline is based on
case reports, case series, and expert opinions. Therefore as per the Appraisal of
Guidelines for Research & Evaluation (AGREE) Instrument II the level of evidence is
mostly at level D.
Profile of NPS users - NPS use has been observed in a distinctive group of population.
Hence, identifying this group would be important for managing suspected NPS toxicity.
Demographically most of them are adolescent or young adult males, with mostly
homosexual orientation. A majority of these individuals are also regular cannabinoids
or cocaine users. A substantial majority uses these drugs in the night clubs and procures
it through online purchasing.
Assessment of suspected case of NPS intoxication - Most of the patients with NPS use
would be encountered in the emergency departments. Manifestations of the adverse
effects due to these groups of drugs could be psychiatric or due to physiological.
Detection of such cases with NPS intoxication/toxic effects depends on obtaining a
recent intake of these substances. However, many a time history is not available or even
there is a history of recent ingestion, effects of these drugs could be modified by other
confounding variables due to simultaneous intake of other illicit substances.
Nevertheless there are certain clinical indicators which suggest NPS toxicity. A
sympathomimetic toxidrome is almost universal for all types of NPS (especially for
synthetic cannabinoids/cathinones). NPS intoxication might also present with
behavioural manifestations like, sudden onset unprecedented violence, suicidal
behaviour and hallucinations. In addition to these, there are demographic indicators as
mentioned already. In presence of these clinical indicators, laboratory analysis of
biological specimens should be sent for identification of NPS or other illicit substances.

However, major limitations of these laboratory procedures are the availability and the
time and expertise required to analyze and interpret results. In addition to direct
detection of the chemical in the sample, there are certain laboratory changes (like
hyperglycemia, hyponatremia, increased creatinine, changes in ECG) that have been
detected in Spice/Bath salt intoxication. Although these all are non-specific changes
which can happen in plethora of other medical conditions, in the presence of other
clinical/historical evidence these laboratory parameters might have some supportive
role to play.
Management of NPS intoxication/toxicity - Diagnosis of exposure, intoxication, and or
toxicity can be challenging, as patients may be unable to share key historical details. The
emergency and acute care physician must maintain a high index of suspicion for these
toxins. No specific antidotes exist for NPS toxicity. Hence, management is always
supportive. Most cases could be managed in the emergency with regular
monitoring/observation. Patients need to be admitted in the intensive care unit, if they
required to be intubated, with severe hyperthermia, recurrent seizures, coma, and
arrhythmia. In case patients have predominant psychiatric symptoms, they could be
transferred to a special psychiatric unit. Management might be grossly divided into
three categories, treatment of sympathomimetic toxicity, behavioural/psychiatric
problems, and withdrawal symptoms. The mainstay of treatment is benzodiazepines.
Anti-psychotics are not the first preferred option for psychotic symptoms or violence, as
these might lower the seizure threshold.
Treatment of withdrawal - Treatment of withdrawal symptoms is supportive and
gradual dose reduction is not necessary.
Long term management - Evidence is limited to make any comments.

1. INTRODUCTION
New psychoactive substance (NPS) is the term which encompasses a huge rubric of
chemicals with pharmacological properties and clinical effects resembling a known
illicit substance.1 The actual 'image' of these groups of psychoactive substances
masquerades as common, apparently harmless consumer goods (like bath salts,
incense, plant food, herbal products, etc.) or aura of science (research products) or
substances which are 'legal' (hence also known as legal highs). The last point is
important because many of these 'NPS's are still elusive to the legal watchdog agencies
and thus could not be brought under proscription. This might be as a result of the
discrepancy between ever emerging, fast growing innovative chemical tampering of
NPS and slow, tedious, and convoluted drug policy.2 Thus the data regarding NPS are
still underestimated and underappreciated.
Recognizing the salience of NPS, European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA) was perhaps the first official organization to respond and furnish
a special investigation report which described the new emerging phenomenon of NPS.3
During 2012, 57 psychoactive substances were officially notified for the first time in the
European Union, with the EU's early warning system reporting the appearance of more
than one new psychoactive drug on the market every week.4 The recent number has
reached up to 500.4 Moreover NPS are usually sold online through an amount of
unregulated websites and are almost unknown to health professionals who may not be
technically up to date/conversant, given the typical absence of up-to-date scientific
literature and reliable sources of information.1,5,6 Thereafter classifying this ever
increasing, broad, and mixed bag of NPS has been attempted by United Nations Office
of Drug and Crimes (UNODC), as ketamine, Piperazines, Synthetic Cathinones,
Synthetic cannabinoids, and plant based substances (Kratom, Salvia divinorum) (Panel
1).7 This could one hand improve research and recognition of these groups of
substances but on the other might limit the exploration by drawing an artificial
boundary.
The initial surveillance and tracking of NPSs took place in the European Union (EU) via
an early warning network (Reitox), as well as an innovative Internet investigative project
(Psychonaut) searching proactively for emerging patterns of drug abuse. A similarly
coordinated early warning network exists in the USA called the Community
Epidemiology Work Group (CEWG). The CEWG identified the emerging Synthetic
cannabinoids (K2) epidemic in the Midwestern USA in 2010.7 In March 2011, the
United States Drug Enforcement Administration (DEA) temporarily placed 5 synthetic
cannabinoids (SC) into Schedule 1 of the Controlled Substances Act “to avoid imminent
hazard to the public safety.8Amongst all exposures reported to American Association of
Poison Control Centers between January 1, 2009, to April 30, 2012, Bath salts and
synthetic THC exposures totaled 7467 and 11561, respectively. Bath salts exposures
were 0 in 2009, 298 in 2010, and 6062 in 2011. Synthetic THC exposures were 14 in

2009, 2821 in 2010, and 6255 in 2011.9 This data although might represent the
minuscule fraction of the actual threat definitely represent an increasing trend in the use
of NPS (Bath salt and Spice to be precise).
For a clinician or a psychiatrist all these data could only be meaningful if the relevance
of NPS in clinical practice could be demonstrated either in the form of health hazards or
addictive potential. In the index chapter, we will be discussing about their health
hazards at length. However, only handful of published literature addresses the issue
regarding the addictive potential. A study amongst US dance drug users reported
mephedrone, when used intranasal, to be perceived as more addictive and more risky
than cocaine.10 A strong subjective 'intoxicating effect' of Spice has been demonstrated
in another study.11 More studies are needed to settle this important issue.
Panel 1: Classification of New Psychoactive Substances (NPS) by UNODC4

(but see SPECIAL NOTES FOR INDIAN SCENARIO at the bottom of the panel)
1
Ketamine
l
Piperazines-
l BZP, mcPP, TFMPP
Synthetic
l cathinones (Commercial or colloquial name: Bath salt)-
Mephedrone,2 Flephedrone, MDPV, Naphyrone
Synthetic
l cannabinoids (Commercial or colloquial name: Spice)- JWH-018,
JWH-073, JWH-200, CP-47,497, and (C8)-CP47,497
Plant
l based substances- Kratom, Salvia divinorum
Amino-indanes
l (Commercial or colloquial name: 'pink champagne')- 2-AI
Tryptamine(Commercial
l or colloquial name: 'Foxy-methoxy' or 'alpha o
alpha')- 5-MeO-DMT, 5-MeO-DPT, AMT, 4-AcO-DMT
Other
l substances- 1,3-dimethylamylamine (DMAA)
SPECIAL NOTES for Indian scenario:
1. Since November 2013, ketamine hydrochloride has been placed in the
Schedule X of the Drugs and Cosmetics Rules (Sixth Amendment, 2013),
meaning thereby that, in view of of its serious abuse potential, it is now placed
under the most stringent schedule though still legal to prescribe with prescribed
precautions
2. Since February 2015, mephedrone and its salts and preparations have been
placed in Schedule I of the Psychotropic Substances of the Narcotic Drugs and
Psychotropic Substances (Amendment) Rules, 2015, thus making their use etc.
illegal other than for medicinal and scientific purposes as per the provisions of
the NDPS Act 1985.

2. SCOPE AND METHODOLOGY OF THE GUIDELINE

In our opinion it might be too early to formulate a clinical practice guideline for the
management of NPS as the evidence available so far is entirely based on case reports,
case series and a few surveys. Hence, we thought of providing an overview on the
profile of NPS users, methods of detection of NPS in body samples and the health
hazards associated with the NPS use; all of which are relevant for the screening,
assessment and treatment of NPS 'intoxication' which is practically the only formal
diagnosis we could vouch for at the present moment. Moreover, as already has been
defined, the index chapter will be focused on two NPS i.e. Synthetic cannabinoids and
Synthetic cathinones.
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) to identify published
meta-analysis, reviews, open-label trials, randomized double-blind trials, placebo-
controlled trials, and case reports written in English, focusing on the synthetic
cannabinoids and cathinones. In addition, we have searched Scopus, Google Scholar,
and PsychInfo to identify any other study missed. The following keywords were used:
synthetic cannabinoids, synthetic cathinones, Spice addiction, Bath salts addiction,
New Psychoactive Substance (NPS). The search was conducted on 7th June, 2015. Only
selection of synthetic cannabinoids and clinical trial had yielded no results relevant to
this chapter (barring results on clinical efficacy of synthetic cannabinoids). When we
customized and broadened our search by including all article types and tried to found
out literature before 2011, once again there was no relevant result gathered; however,
2011 onwards we could locate total 600 studies (including 90 narrative reviews).
However, more than half of these articles are on role of synthetic cannabinoids in
various disorders. The keyword New psychoactive substance and synthetic cathinones
yielded 586 and 152 results overall.
3. PROFILE OF NPS USERS
A central question is regarding the profile of users of NPS. The speculative users of NPS
could be younger generation or professionals who might be using to obviate the risk of
detection. The reason for using could be accidental or deliberate to have the legal high.
Questions are asked whether NPS is a supplement or substitute of other illicit
substances. To answer these questions maximum data are available for Spice (Synthetic
cannabinoids). Studies across the Continents have revealed that Spice is an international
phenomenon used primarily by adolescents and young adults and a gender gap, with
men more than twice as likely to use Spice than women.12-13 Data from the American
Poison Research Centre has almost demonstrated similar findings for Spice with a
slightly young user profile (13-19 years). The same report has shown the most common
users of Bath salts to be in the age range of 20-29 years. Intentional abuse and inhalation
were most common reason for and mode of exposure, respectively.9 Another survey on
Spice revealed that in about one in five individual it was the preferred drug and primary

reasons for use were curiosity, positive drug effect, relaxation, and to get high without
having a positive drug test.14 Moreover, acute subjective effects were reported to be
similar to known effects of cannabis. In addition to this survey, a recent report has shown
that use of Spice is widely prevalent amongst cannabis users.15 Whether NPS is a
supplement or substitution for the existing illicit substance use, to find out an answer to
this important issue, a study has been conducted in the UK. The results show that NPS
are likely to be added to drug repertoires rather than replacing it, particularly amongst
experienced users with consequent health risks for individuals and resource
implications for services.16 As college goers fall in the vulnerable age group for Spice,
studies amongst college students appear to be well justified. In a longitudinal study
conducted in two colleges in the US has revealed that weighted lifetime prevalence of
K2 and Spice use at college entry was 7.6%. An additional 6.6% of students reported first
use during college. By the cohort's fourth year, 17.0% reported lifetime K2 and Spice
use. K2 and Spice use at college entry was associated with sensation seeking; hookah,
marijuana, and illicit drug use; and low religiosity, which further substantiates the
previous findings from the general population or poison centers.17 A potential space in
which NPS might be used is in the discos. In a study from US night life scenes, 8.2%
reported use of synthetic cannabinoids and 1.1% reported the use of mephedrone. Gay
and bisexual men reported higher prevalence of mephedrone use. Latinos reported
higher prevalence of synthetic cannabinoid use.18 A study of mephedrone use among
dance drug users in the UK suggests that users of this substance are likely to be younger
and male. Over 40% of these UK dance drug users reported the use of mephedrone.
Additionally, other research indicates that many users in the UK continued the use of
mephedrone after its ban despite a subsequent price increase, suggesting that the
substance may be becoming entrenched within a broader class of club drugs within
some scenes.10It has been cited as popular in some European nightclubs, such as in
London, even after its prohibition with prevalence in one sample of attendees of gay-
friendly clubs at 41%.9 From these studies it is quite apparent that in both sides of the
Atlantic, Spice and mephedrone are used extensively by a special group of population.
Due to difficulties with its detection through standard testing, it may be an attractive
substance of abuse for military personnel. However, few studies have examined the
consequences of its use in this population. In one of the US surveys conducted amongst
treatment seeking military personnel, 11% reported using SC in the last 90 days and
more than 65% of them reported Spice as their preferred drug.19 (Panel 2)

Panel 2: Profile of individual with New Psychoactive Substance (NPS) use

Age
l - adolescents (Spice users are younger than others like users of Bath salt)
Gender-
l Male> Female
Vulnerable
l users- people with cannabis/cocaine use
Special
l demographic risk population- Gay and Lesbian, military personnel
Important
l locus of use- night clubs
4. ASSESMENT OF SUSPECTED CASES OF NPS INTOXICATION

4.1 Clinical assessment
Most of the patients with NPS use would be encountered in the emergency
departments. Manifestations of the adverse effects due to these groups of drugs could be
psychiatric or due to physiological. Data regarding their 'toxic' effects and management
are retrieved from the surveys conducted by National level Poison Centers and from
case reports and case series. Hence the level of evidence is still a matter of debate and
conjecture.
Detection of such cases with NPS intoxication/toxic effects depends on obtaining a
recent intake of these substances. However, many a time history is not available or even
there is a history of recent ingestion, effects of these drugs could be modified by other
confounding variables due to simultaneous intake of other illicit substances.20
Nevertheless there are certain clinical indicators which suggest NPS toxicity (Panel 3). A
sympathomimetic toxidrome is almost universal for all types of NPS (especially for
synthetic cannabinoids/cathinones). Commonly reported effects include diaphoresis,
palpitations, muscle tension or spasms, and bruxism (jaw clenching). In severe cases
sympathomimetic toxicity is manifested by neurological and cardiovascular clinical
features. The use of bath salts has been associated with cardiac arrhythmias.21 Acute
drug toxicity is the leading cause of synthetic cathinone-induced fatality. Concomitant
consumption of synthetic cathinones and other drugs have been reported in numerous
fatalities.22-25 Concurrent use of synthetic cathinones with other stimulants leads to
significantly greater monoamine toxicity, which may underlie the high frequency of
polydrug use fatality associated with the synthetic cathinones.26 Other common and rare
features of toxicity have been mentioned in the Table 1.
Toxicity of these substances depends on the amount and mode of intake, concomitant
intake of other illicit substances, and time lapsed. Most designer stimulants are taken
intranasally but may be consumed orally or via intravenous or intramuscular injection.
Mephedrone is not suitable for smoking. Anecdotally, the effects generally start about
10-20 minutes after dosing, peak at 45-90 minutes, last 2-3 hours, and then decrease
over 6-12 hours. Users may consume multiple doses during a session to prolong the
desired effects.20 Synthetic cannabinoids are primarily smoked via a joint, bowl, or

water pipe, although they can be consumed orally or intranasally. Acute effects are
similar to cannabis, including alteration in mood, conjunctival injection, and
tachycardia. Effects are reported to start within 10 minutes after inhalation, and most
effects appear to dissipate 2-6 hours after use.20
Following physical parameters must be examined in a suspected case of NPS use: body
temperature, pulse (tachycardia), blood pressure (hypertension), monitoring urine
output (oliguria/ anuria), general physical examination (for diaphoresis, needle marks,
ecchymosis, conjunctival injection), ENT examination (nasal perforation, poor oral
hygiene), examination for muscle tenderness (rhabdomyolysis), abdominal
examination (hepatomegaly and tenderness),and neurological examination (clonus).
Acute onset agitation or hallucination (or other psychotic symptoms) in a patient
without any prior psychiatric history and with a history of recent drug/herbal product
consumption must raise the suspicion of NPS toxicity. Synthetic cathinone
hallucinations are frequently auditory and tactile in nature and paired with psychoses
that can be severe and long lasting; many patients are admitted days after cessation of
drug use and psychotic symptoms persist for several days thereafter while receiving
treatment.27-28
Table 1. Physical findings associated with New Psychoactive Substance (NPS) use
Body systems Physical findings/ Suspected NPS Association with
Clinical syndromes the NPS
General Hyperthermia Synthetic hallucinogens, Intoxication
bath salts
Cardiac Tachycardia, Any NPS Recent use
Hypertension Bath salts, synthetic
Chest pain: might cannabinoids
indicate cardiac
ischaemia/myocarditis
Neurologic Clonus Synthetic hallucinogens Recent use
Seizures Bath salts, synthetic Intoxication
hallucinogens, synthetic
cannabinoids
Head & neck Conjunctival injection Synthetic cannabinoids Recent use

Smoky chemical smell Any smoked NPS
on breath
Epistaxis, nasal septal Bath salts Intra-nasal use
perforation
Jaw clenching, teeth Bath salts Intoxication
grinding (bruxism)
Renal Acute kidney injury Synthetic cannabinoids Recent use

Body systems Physical findings/ Suspected NPS Association with

Clinical syndromes the NPS
Gastrointestinal Nausea, vomiting Synthetic cannabinoids Recent use or
Enlarged and/or tender Any injected NPS withdrawal
liver: Acute hepatitis
Musculoskeletal Muscle spasms Bath salts Intoxication
Limb swelling and pain: Bath salts, synthetic
rhabdomyolysis hallucinogens
Skin Diaphoresis Bath salts Recent use
Ecchymosis Synthetic hallucinogens Recent use or
Fresh needle marks, Any injected NPS intoxication
track marks
Psychiatric Agitation Any NPS Recent use
Psychosis (with or Recent use or
without hallucinations) intoxication
Self mutilation Synthetic cathinones
Adapted from Weaver et al., Designer drugs 2015: assessment and management.
Addict Sci Clin Pract. 2015; 10(1): 8.20
Panel 3: When to suspect New Psychoactive substance (NPS) toxicity?
Historical
l evidence- recent intake of some unknown commercial herbal
product purchased online or definitive history of consumption of Spice/Bath
salts; individual with history of regular intake of cannabis, stimulants or other
psychoactive substance
Demographic
l pointers- young adults or adolescent males, with a homosexual
orientation hailing from a night club
Evidence
l from physical findings- conjunctival injection, odor of smoky
chemical in the breath, perforated/ulcerated nasal septum, increased body
temperature, palpitation, high blood pressure, decreased urine output,
bruxism, muscle tenderness
Suggestive
l clinical features- seizure in an individual, who is a known
cannabis user; acute renal failure and rhabdomyolysis without any apparent
physical cause
Behavioural
l indicators- acute onset agitation, hallucination, self mutilating
behaviour in an individual without any prior psychiatric history
4.2 Laboratory assessment

Detection of NPS is considered at two levels. First, in the suspected commercially
available products and second which is important for clinicians, detection in biological

samples of subjects supposedly had consumed some of these products before landing
up in the emergency. For the purpose of current practice guideline, by the phrase
detection in laboratory, would be referred to the latter. Detection of NPS in the
laboratory is always a challenging task. Whereas cases of intoxication and death have
been reported, the phenomenon appears to be largely underestimated and is a matter of
concern for Public Health. One of the major points of concern depends on the
substantial ineffectiveness of the current methods of toxicological screening of
biological samples to identify the new compounds entering the market.29 As stated
earlier, the focus of the discussion would be on synthetic cannabinoids/cathinones (SC).
There are a number of unique challenges to the laboratory detection of these substances
present in the urine, oral fluid, and serum samples of people who have consumed
Spice/Bath salt.
l Contains synthetic cannabinoids/cathinones from different chemical classes
l Contains minimal amount of these substances
l Composition that is constantly changing
Therefore, a laboratory test that is to be of clinical utility would require a single or battery
of tests that could detect cannabinoids/cathinones or their metabolites belonging to
several chemical classes. The most common biological sample analyzed for the
assessment of SCs is blood. Other samples which have been tested are urine and oral
fluid.20
Several synthetic cannabinoids including JWH-018 and many of their downstream
metabolites can be measured in the serum through liquid chromatography tandem mass
spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC/MS).
However, LC-MS/MS and GC/MS methods require extraction, concentration, or
derivation techniques that are time consuming. There are no commercially available
laboratory tests for the detection of synthetic cannabinoids. These tests cannot be
performed on-site at most institutions. Thus, the results would not be immediately
available and would be unlikely to inform clinical decision-making.30-32 Synthetic
cathinones can be identified using gas chromatography–mass spectrometry or liquid
chromatography–mass spectrometry techniques. They can be measured in blood,
urine, and stomach contents in both pre and postmortem specimens. Correlation of
concentrations with clinical effects is not well understood. Blood concentrations of
methedrone in specimens taken from suspected drug offenders ranged in one series
from 0.2 to 4.8 ìg/g blood. Mephedrone concentrations in urine specimens taken after
use in the preceding 24 h ranged from 0.6 to 7.35 mg/Ml. Synthetic cathinones can be
analyzed in hair. A rat model suggests that cathinone and methcathinone are poorly
incorporated into hair, but that methylone is well incorporated.33-36
As already mentioned one of the major limitations of these laboratory procedures is the
time and expertise required to analyze and interpret results. A recent study has
demonstrated the feasibility of a simple liquid chromatography-tandem mass
spectrometry (LC-MS/MS) screening procedure for NPS in blood. Simultaneous

screening for 143 substances (including SCs) from different groups would be possible.
The limits of detection (LODs) estimated for 104 compounds were in the range 0.01-
3.09 ng/mL, which is reasonably good. However, the extraction recoveries determined
for 32 compounds were from 1.8 to 133%.37 Despite having some limitations, this study
should promote further research.
In addition to direct detection of the chemical in the sample, there are certain laboratory
changes which have been detected in Spice/Bath salt intoxication (Table 2). Although
these all are non-specific changes which can happen in plethora of other medical
conditions, in the presence of other clinical/historical evidence these laboratory
parameters might have some supportive role to play.
Recommendations: If a patient presents with sympathomimetic toxidrome and
presence of any red flag signs as mentioned in Panel 3 (Historical, demographic,
physical, clinical, and behavioural), following investigations could be advised:
l Send a laboratory test for synthetic cannabinoids/cathinones (SC) [if available]
l Urine drug screen for cannabinoids, amphetamines, cocaine, heroin
l A positive test for SC- substantiate the diagnosis
l Negative test for SC- not rule out NPS toxicity
l Negative other drug screen- suggestive evidence
Table 2. Laboratory changes associated with the use of
synthetic cannabinoids/cathinones
Laboratory findings Observed values Associated psychoactive
substance
Hyperglycemia 170 to 220 mg/Dl Synthetic cannabinoids
Hypokalemia 2.3 to 3.5 mmol/L Synthetic cannabinoids
Hyponatremia 120-135 mmol/L Synthetic cathinones
Hyperkalemia >5.2 mmol/L Synthetic cathinones
Elevated Creatinine 3.2-21.0 mg/dL Synthetic cannabinoids,
Synthetic cathinones
Acidosis pH of 7.24 and a pCO2 of 63 Synthetic cannabinoids,
Synthetic cathinones
Elevated Creatinine 867 to 2649 U/L Synthetic cannabinoids,
Phosphokinase Synthetic cathinones
Elevated White Blood Cell 13,000 to 19,000 cells per Synthetic cannabinoids
Count microliter
Adapted from Spadarna et al., Spicing thing up: synthetic cannabinoids.
Psychopharmacology (Berl). 2013; 228(4): 525–540.33

5. MANAGEMENT OF SYNTHETIC CANNABINOIDS/CATHINONE

INTOXICATION/TOXICITY
Diagnosis of exposure, intoxication, and or toxicity can be challenging, as patients may
be unable to share key historical details. The emergency and acute care physician must
maintain a high index of suspicion for these toxins when evaluating patients with signs
and symptoms of sympathomimetic toxicity and all those pointers mentioned
elsewhere (Panel 3) must be kept in mind. No specific antidotes exist for NPS toxicity.
Hence, management is always supportive.
5.1 Treatment settings:
Usually cases of NPS toxicity are encountered in the emergency departments. Most
cases could be managed in the emergency with regular monitoring/observation and till
the disappearance of physical symptoms or correction of underlying
metabolic/physiological disturbances. Patients could be discharged once they are
stabilized.38 Those with persistent vital sign, neurologic, or psychiatric abnormalities
should be admitted. Patients need to be admitted in the intensive care unit, if they
required to be intubated, with severe hyperthermia, recurrent seizures, coma, and
arrhythmia. 39 In case patients have predominant psychiatric symptoms like
hallucinations, hostility, suicidal tendencies, they could be transferred to a special
psychiatric unit.40 Admission to the Medical ward might be necessary in case of renal
failure and acute hepatitis. In a case series of 35 patients who presented to the ED after
using “bath salts,” 26% were admitted to an intensive care unit, 14% to the medical
floor, and 9% to the psychiatric unit.41
5.2 Management of sympathomimetic toxidrome:
Physical signs of most of the NPS intoxication (especially Synthetic cathinones) are
consistent with sympathomimetic toxicity, which include hypertension, tachycardia,
hyperthermia, dehydration, and psychomotor agitation. The most commonly reported
adverse symptoms include palpitations, headache, chest pain, trismus, bruxism,
tremors, and insomnia. Current practice is based on the treatment experience with other
sympathomimetic agents, and supportive care is the mainstay of therapy. Aggressive
sedation with benzodiazepines is indicated as needed for agitation, seizure,
tachycardia, or hypertension. If hypertension persists, it is reasonable to treat with
titratable vasodilators (i.e., nitroglycerin or sodium nitroprusside). Beta blockade
should be avoided due to potential exacerbation of hypertension due to unopposed
alpha-adrenergic stimulation. Significant hyperthermia may require passive or active
cooling if not resolved with anxiolysis and sedation.42-43 The recommendations have
been mentioned in the management algorithm.
5.3 Management of psychiatric symptoms:
Unprecedented hostility, violence, and suicidal behaviour could be present during
Spice or Bath salt intoxication. Although not systematically studied, during these

episodes the safety of the patient and the people around would inevitably become the
cornerstone of treatment. Patients need to be isolated in a safe and calm place with
minimal environmental stimulation. Benzodiazepines could be prescribed if violence
could not be managed by conservative means. The dose and the choice of
benzodiazepines remain speculative. However, based on the treatment experience
with other violent patients, perhaps lorazepam in a slow intra-venous route with
periodic monitoring of vitals might be considered.38,44
Psychosis due to synthetic cannabinoids (SC) and cathinone intoxication have been
managed with monitored observation. For psychopathological clinical features,
benzodiazepines have been used to treat anxiety, agitation, and seizures.
Antipsychotics are second-line agents for agitation, due to the lowered seizure
threshold with use of cathinone and phenethylamine designer drugs. Sedation may be
required if the patient is markedly agitated and at risk for harm to self or health-care staff.
Since some designer drug-associated psychosis may be severe and require prolonged
inpatient treatment, psychiatric consultation is indicated, in particular for those with
persistent symptoms.20,45
If marked psychiatric symptoms persist longer than one or more weeks after
discontinuation, the patient should be evaluated carefully to determine whether he or
she has a co-occurring primary psychiatric disorder, which then should be treated with
specific therapy. Treatment of prolonged anxiety, depression, or psychosis is the same
as when these conditions are not associated with recent designer drug use.46-47
The recommendations have been mentioned in the management algorithm.
5.4 Management of withdrawal symptoms:
Abrupt discontinuation of stimulants or hallucinogens does not cause gross physiologic
sequelae, so they are not tapered off or replaced with a cross-tolerant drug during
medically supervised withdrawal. Abrupt discontinuation of SC could result in
withdrawal symptoms such as nausea and irritability, similar to that with cannabis
cessation. However, there is no indication for pharmacologic replacement (e.g.,
dronabinol), since SC withdrawal is not life-threatening. Patients can be treated with
supportive care by intravenous fluids and antiemetics if necessary.48-49
The recommendations have been mentioned in the management algorithm.

Management algorithm
Patient in emergency with features of

sympathomimetic toxidrome (high pulse, blood
pressure, tremor, insomnia, anxiety) [D] What
does this recommendation mean?
Send a laboratory test for synthetic
cannabinoids/cathinones (SC) [if available]
Urine drug screen for cannabinoids,
Presence of any red flag signs as mentioned in amphetamines, cocaine, heroin
Panel 3 (Historical, demographic, physical,
A positive test for SC- substantiate the diagnosis
clinical, and behavioural) [D]
Negative test for SC- not rule out NPS toxicity
Negative other drug screen- suggestive evidence
[D]
(A) Shift to ICU (C) Shift to Medical unit

Severe
l hyperthermia, Acute
l hepatitis,
l Recurrent seizures, l Acute renal failure
l Coma, [D]
l Arrhythmia [D]
(B) Shift to Psychiatry unit (D) Manage in the

l Violence, hostility (if not emergency
managed conservatively) If neither (A) nor (B) or (C)
l Suicidal behaviour is present
l Psychotic symptoms [D]
(especially if persistent)
Sympathomimetic toxidrome: Conservative management

Physical
l monitoring- blood pressure, pulse, urine output, body temperature
l Investigations- ECG, Serum electrolytes, urea/creatinine, blood glucose
l Symptomatic management- Benzodiazepines [C/D] for agitation; nitroglycerine for hypertension
[D]
Psychiatric symptoms: (violence, hallucination, suicidal behaviour)

Conservative
l management- Providing a calm/supportive/non-threatening environment
l If not controlled- Benzodiazepines
l If not controlled with benzodiazepines- Second generation anti-psychotics (Low dose)
l For persistent psychotic symptoms- consider possibility of an independent psychiatric disorder
[D]
Withdrawal symptoms:
l Abrupt stoppage of the substance (NPS)
l Manage anxiety with benzodiazepine
l Manage nausea/vomiting with anti emetics
[D]

6. LONG TERM TREATMENT FOR NPS USE DISORDERS

Data are grossly insufficient to comment on the feasibility, necessity, and efficacy for the
long term treatment of NPS use disorders. Although there has been some evidence
suggesting the addictive (or dependence producing) potential of NPS, the current
literature is inadequate to make a conclusive impression.10,11 However, hospitalization
for the adverse effects of designer drugs affords an excellent opportunity (teachable
moment) for advising patients to decrease their substance use and for engaging them in
treatment.50 Explaining about the risks and the harms associated with such drug use,
exploring about patient's ambivalence and resolving the same, encouraging healthy
choice and a special focus on harm reduction could be implemented during the time of
hospitalization. Long-term treatment of designer drug use disorders likely involves
similar components to that of other types of addiction treatment, including behavioural
components, such as individual and group counseling with cognitive-behavioural
therapy, motivational enhancement therapy, and 12-Step self-help group facilitation.
Family members should be considered as part of the treatment program, in particular
when treating adolescents or young adults. Unfortunately, pharmacologic treatment
data to guide management of those with designer drug use disorders are unavailable.
Although the empirical evidence needed to substantiate the effectiveness of these
strategies is lacking, extrapolation of other literature related to this area provides an
indirect validity.20,51
7. CONCLUSION
New psychoactive substance (NPS) includes a wide range of chemicals (either
manufactured in the laboratory or derived from plant products) which are definitely
physically harmful and perhaps addictive. The number and type of substances are
rapidly growing and emerging, making the list ever proliferative and almost impossible
to reproduce. Based on epidemiological data and clinical pragmatism, the index
guideline had included two of the most important NPS namely, synthetic cannabinoids
(Spice) and synthetic cathinones (Bath salts). No randomized controlled trials have been
undertaken till date. Overall the area is riddled by gray and dark zones. Current research
has been aimed at finding the profile of users, detection of these substances in biological
fluids, manifestation and management of toxicity resulting from the
intoxication/overdose of these substances. More research is required to give more than
an impressionistic overview in these areas. New studies are warranted exploring the
addictive potential and long term course, outcome and management of NPS users.
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Drug Distribution and Interpretation of Results. J Anal Toxicol. 2013
24. Maskell PD, De Paoli G, Seneviratne C, Pounder DJ. Mephedrone (4-
methylmethcathinone)-related deaths. J Anal Toxicol. 2011;35:188–191.
25. Schifano F, Corkery J, Ghodse AH. Suspected and confirmed fatalities associated with
mephedrone (4-methylmethcathinone, "meow meow") in the United Kingdom. J Clin
Psychopharmacol. 2012;32:710–714.
26. Angoa-Perez M, Kane MJ, Francescutti DM, Sykes KE, Shah MM, Mohammed AM, et
al. Mephedrone, an abused psychoactive component of 'bath salts' and
methamphetamine congener, does not cause neurotoxicity to dopamine nerve
endings of the striatum. J Neurochem. 2012;20:1097–1107.
27. Kasick DP, McKnight CA, Klisovic E. "Bath salt" ingestion leading to severe
intoxication delirium: two cases and a brief review of the emergence of mephedrone
use. Am J Drug Alcohol Abuse. 2012;38:176–180.
28. Stoica MV, Felthous AR. Acute Psychosis Induced by Bath Salts: A Case Report with
Clinical and Forensic Implications. J Forensic Sci. 2013
29. Favretto D, Pascali JP, Tagliaro F. New challenges and innovation in forensic
toxicology: focus on the "New Psychoactive Substances". J Chromatogr A. 2013;
1287:84-95.
30. Frison G, Gregio M, Zamengo L, et al. Gas chromatography/mass spectrometry
determination of mephedrone in drug seizures after derivatization with 2,2,2-
trichloroethyl chloroformate. Rapid Commun Mass Spectrom. 2011;25:387–90.
31. Maheux CR, Copeland CR. Characterization of three methcathinone analogs: 4-
methylmethcathinone, methylone, and bk-MBDB. DEA Microgram J. 2010;7:42–9.
32. Wissenbach DK, Meyer MR, Remane D, Philipp AA, Weber AA, Maurer HH. Drugs of
abuse screening in urine as part of a metabolite-based LC-MS(n) screening concept.
Anal Bioanal Chem. 2011;400:3481–89.
33. Spaderna M, Addy PH, D'Souza DC. Spicing things up: synthetic cannabinoids.
Psychopharmacology (Berl). 2013; 228:525-40.

34. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J
Med Toxicol. 2012;8:33-42.
35. Torrance H, Cooper G. The detection of mephedrone (4-methylmethcathinone) in 4
fatalities in Scotland. Forensic Sci Int. 2010;202:e62–e63.
36. Lusthof KJ, Oosting R, Maes A, et al. A case of extreme agitation after use of
mephedrone in the Netherlands. Forensic Sci Int. 2011;206:e9395.
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psychoactive substances by liquid chromatography-tandem mass spectrometry. Drug
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Toxicol (Phila) 2011;49:431–433.
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characteristics of mephedrone toxicity reported to the UK National Poisons
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kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol.
2012;8:15-32.
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2011;60:624–7.
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Toxiciology Section 2011, Newsletter.
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associated with analytically confirmed recreational use of 25I-NBOMe: case series.
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methoxyphenyl) methyl] ethanamine (25I-NBOMe): clinical case with unique
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COCAINE
Subodh B.N.
Aniruddha Basu
On behalf of
2016
Cocaine
CONTENTS
Executive Summary
1. Introduction
1.1 Epidemiology
1.2 Pharmacology
1.3 Mechanism of action
1.4 Consequences of cocaine use
2. Cocaine use disorders
3.1 Scope of the Guidelines
3.2 Methodology of Guideline development
4. Review of treatment modalities
4.1 General Issues
4.2 Treatment Aims / Goals
5. Assessment of cocaine use disorders
5.1 Brief Overview
5.2 Clinical History
5.3 Physical Examination
5.4 Instruments
5.5 Investigations
6. Short term management
6.1 Management of cocaine intoxication
6.2 Management of cocaine withdrawal
7. Long term management of cocaine use disorders
7.1 Pharmacological agents
7.1.1 Topiramate
7.1.2 Modafinil
7.1.3 Disulfiram
7.1.4 Stimulants
7.1.5 Anticonvulsants
7.1.6 Antipsychotics
7.1.7 Antidepressants

7.1.8 Dopamine agonists

7.1.9 Cocaine Vaccine
7.1.10 Other medications
7.1.11 Use of Combination Pharmacotherapy
7.2 Psychosocial treatment
7.2.1 Behavioural approaches
7.2.2 Cognitive behavioural therapy
7.2.3 Twelve step facilitation program
7.2.4 Motivational enhancement therapy
7.2.5 Other psychotherapeutic approaches
7.3 Combined psychosocial and pharmacological management
8. Special Population
8.1 Pregnancy
8.1.1 Evidence Base
8.1.2 Conclusion
8.2 Attention Deficit Hyperactivity Disorder
8.2.1 Evidence base
8.2.2 Conclusion
9. Recommendations
9.1 Some issues to be considered before arriving at recommendations
9.2 Recommendations

Cocaine
EXECUTIVE SUMMARY
Cocaine a classic stimulant has emerged as one of the most common drugs used
worldwide. Cocaine use disorders are associated with high mortality and morbidity
worldwide. There is not much data on use of cocaine in India. Recently in last few years
there are literature on use in media and one case series. As cocaine dependence
syndrome like any other addictive disorders is a chronic relapsing and recurring
condition, patients with cocaine use disorders will require a comprehensive
multipronged care for continuous and prolonged period of time. An integrated bio-
psychosocial approach to care is needed to address several aspects of the treatment. An
active collaboration with the family while planning and delivering treatment is
required.
The main goal of treatment is to maintain abstinence and if not possible decrease the
frequency and severity of relapses and maximize functioning in between. The goals of
treatment vary according to time frame, across individual patients and can be revised
from time to time. It has been broadly divided into short term and long term goals. The
short goals are management of intoxication, management of withdrawal symptoms,
motivation enhancement, treatment of acute medical sequel and crisis intervention.
Long term treatment goals are relapse prevention, maintenance of abstinence,
occupational rehabilitation, social reintegration, abstinent life style and improving the
quality of life of a person. This guideline will focus on the evidence available for the
management of intoxication, management of withdrawal symptoms, and management
of cocaine dependence. The current guideline used the AGREE II guidelines as template
for proposing the guideline.
Assessment of Cocaine use disorders
A thorough and good assessment will help in diagnosing, establishing rapport,
motivating the person and in formulating the plan of the management. The goal of
assessment also varies in different phases of the treatment. During the first contact it is to
establish rapport, diagnosis and plan of management, and during intervention it is
monitoring the progress and assessing abstinence. The goal also depends on the
context, motivation and cooperativeness of the client. If the client is uncooperative the
aim of assessment is to retain the client in the treatment. During this time the information
can be collected in pieces and information can be added when patient is co-operative.
A detailed assessment should include substance related factors (age of initiation,
frequency, amount, tolerance, craving, withdrawal symptoms, salience, last dose,
motivation, consequences of substance use), history of other substance use, physical
and psychiatric comorbidity if any, abstinence related factors (past abstinence,
duration, reasons for relapse, past treatment/s, methods used for controlling craving). It
also includes history of high risk behaviours, presence of any externalizing disorders,

physical and psychiatric comorbidity, family history of substance abuse and psychiatric
illness, assessing social support, current living arrangements and reasons for current
visit. A thorough physical examination is needed to assess for intoxication, withdrawal
symptoms and evidence of physical damage due to alcohol use or other substance use.
Investigations are used to confirm the presence of the cocaine, assess the degree of the
physical damage and to confirm the presence of sexually transmitted disorders.
Some issues to be considered before arriving at recommendations
The proposed guideline is based on evidence obtained from developed countries
(particularly USA) and none from India. Manifestations of cocaine intoxication and
withdrawal are non- specific and are mostly self-limiting. Psychosocial interventions
have reasonable evidence base and are recommended for cocaine use disorders.
Short term Management
The short term management is aimed towards medical stabilisation and engaging
patient in process of treatment. The management of cocaine intoxication should include
general assessment as described in 'assessment' with particular emphasis placed on
physical status, mental status, substance use history and associated consequences. The
acute effects of cocaine generally subside with time and they do not warrant any specific
treatment. Specific pharmacological treatment is necessary when there is a history of
recent use of other substance with physical consequences (e.g., respiratory depression,
stroke, arrhythmias, etc.). In mild intoxicated state general measures like reassurance
and maintenance in a safe and monitored environment do decrease external
stimulation. Adequate hydration and nutrition should be provided. After the patient
stabilizes then we need to assess the patient comprehensively and also assess for
withdrawal and further management.
Management of cocaine withdrawal requires constant monitoring of signs and
symptoms of withdrawal. The goals of the withdrawal are a) To relieve patient's
discomfort, prevent the occurrence of more serious symptoms, and forestall cumulative
effects that might worsen future withdrawal; b) To utilise the withdrawal treatment
opportunity to engage patients in long-term management. The withdrawal symptoms
are self limiting. There are no well studied pharmacological agents to relieve symptoms
of cocaine withdrawal. There is some evidence base for dopamine agonists like
amantadine and bromocriptine, propranolol and other drugs. These drugs have given
mixed results. The strength of evidence for these is at best (D) level and needs further
studies for management of cocaine withdrawal.
Long term Management
Cocaine dependence is a chronic illness with lapses and relapses. Medications and
psychosocial strategies are used for promoting abstinence and preventing relapse in

Cocaine
patients with cocaine dependence. All the pharmacological agents used in cocaine use
disorders have been studied along with psychosocial interventions. Hence patients
should use whichever psychosocial approach they think beneficial or is available along
with pharmacological agents.
Psychosocial treatments are the main stay of treatment - contingency management,
community based reinforcement approaches and CBT have the highest efficacy (A).
Other therapies like MET, mindfulness based therapies need further research (C).
Evidence for drug treatment is still preliminary – pharmacological treatment should be
used in combination with psychosocial therapies (A). Modafinil and topiramate are
emerging as prospective medications though currently evidence is not unequivocal and
contradictory evidences exist (C). Currently disulfiram, dopamine agonists,
antidepressants, anticonvulsants (except topiramate), psychostimulants, neither any
combination of these medications are recommended. Cocaine vaccine has been found
to be safe and shown promising results in Phase 1 & 2 research but not so promising
response in Phase 3.

1. INTRODUCTION
Cocaine is one of the classic stimulants is a potent alkaloid derived from the leaves of
coca plant grown by ancient Incas in Andes mountain1. Through explorers it travelled
from South America to Europe. In the beginning of the twentieth century in the United
States coca extracts was banned due to harmful consequences. In mid 1980s two new
forms of cocaine emerged namely freebase cocaine and crack cocaine which are easily
available 'smokable' forms making it easily available to the masses and thereby fuelling
the 'cocaine epidemic'2.
1.1 Epidemiology
Cocaine is one of the most common stimulant drugs used world-wide. The recent World
Drug report states that 13.2 to 19.7 million cocaine users worldwide among adults aged
15 to 64 years (0.3%-0.4%)3. There is significant regional variation and cocaine is the
second most common illicit drug in both the Americas. In Europe it is the most common
illicit stimulant. In the Africa particularly in west and south it is common illicit drug4. For
South Asia it has also entering into the scenario of drug problem. However, it is still
restricted to mostly urban adolescents belonging to high socio-economic class who
mostly visit rave parties or similar social gatherings. A case-series from India illustrates
the recent development of such a problem5. Successive United Nations World Drug
Report had cautioned about the emerging dangers of cocaine in south Asia. The indirect
indicators like drug seizures and media highlights show that cocaine has already
emerged in the India as burgeoning problem particularly among high risk groups like
injection drug users6.
1.2 Pharmacology
Cocaine is extracted from the leaves of the erythroxylon coca by soaking leaves in
organic solvent to form a thick paste7. If it is extracted with hydrochloric acid then the
hydrochloride salt can be snorted, inhaled or taken by intravenous route8. The
hydrochloride salt if treated with cocaine – benzoylmethylecgonine – is a naturally
occurring crystalline alkaloid of the tropane family. It is a relatively small lipophilic
molecule that is absorbed through mucous membranes and alveoli. About one-third of
an oral or nasal dose of powered and up to 95% of an inhaled dose of freebase or crack
cocaine may be bioavailable. Binding of cocaine to plasma proteins is minimal and its
volume of distribution is low. Cocaine has a short half-life of 0.7 to 1.5 hours and is
rapidly metabolized by plasma and liver cholinesterases to the major metabolites of
benzoylecgonine and ecgonine-methyl ester. Benzoylecgonine is a
neuropharmacologically active and cardiotoxic agent. These water-soluble metabolites
are excreted in the urine. The time course of the physiologic effects of cocaine varies
9
with the route of use, form of cocaine used, and concomitant use of other drugs . The
onset of effects occurs most rapidly with inhaled cocaine (3–5 seconds) followed by
intravenous injection (10–60 seconds). The onset of effects is delayed with intranasal

Cocaine
use (within 5 minutes) due to topical vasoconstriction. Conversely, the duration of

effects is longest with intranasal cocaine use (60–90 minutes) and shortest with
inhalation of crack cocaine (5–15 minutes). The short duration of effect with inhalation
may lead to repetitive dosing to maintain desired effects. The frequent concomitant use
of cocaine and ethanol results in the hepatic formation of the active metabolite, coca-
ethylene, which has euphoric and sympathomimetic effects similar to cocaine but may
also have greater toxicity. The longer half-life of cocaethylene (2.5 hours) may prolong
the euphoric effects of cocaine10.
1.3 Mechanism of action
There are several mechanisms of action. The most commonly proposed mechanism is
by acting at dopamine transporter (DAT) and increasing the concentration of
extracellular dopamine in brain reward centres particularly the nucleus accumbens.
This causes acute reinforcing effects11. Cocaine also has sympathomimetic actions in the
peripheral tissues and quinidine like anaesthetic/ type I anti-dysrrhythmic properties. As
a local anaesthetic, cocaine's main effect is to block sodium channels in excitable
tissues, and in massive doses it can interfere with the functioning of the potassium
channels. The mechanism has been reviewed extensively in several reviews12.
1.4 Consequences of cocaine use
Cocaine affects different aspects of life of a person (medical, legal, financial,
interpersonal etc.,) and their family members. Cocaine use is associated with high
mortality and morbidity, reviewed extensively in several reviews13.
2. COCAINE USE DISORDERS
The current nosological approach to cocaine use disorders is14:
DSM-5 ICD-10
Substance use disorder Substance dependence
Substance use disorders span a wide variety of At least three of the following six criteria
problems arising from substance use, and which should have occurred together for at
cover 11 different criteria: least one month or if persisting for periods of
l Taking the substance in larger amounts or less than one month then they have occurred
for longer than the time you meant to together repeatedly within a twelve month
period):
l Wanting to cut down or stop using the
substance but not managing to A. A strong desire or sense of compulsion to
take alcohol
l Spending a lot of time getting, using, or
B. Difficulties in controlling alcohol-taking
recovering from use of the substance
behaviour in terms of its onset,
l Cravings and urges to use the substance termination, or levels of use
l Not managing to do what you should at C. A physiological withdrawal state when
work, home or school, because of alcohol use has ceased or been reduced,
substance use as evidenced by: the characteristic

Continuing
l to use, even when it causes withdrawal syndrome for alcohol; or use
problems in relationships of the alcohol with the intention of
Giving up important social, occupational
l relieving or avoiding withdrawal
or recreational activities because of symptoms
substance use D. Evidence of tolerance, such that increased
Using substances again and again, even
l doses of alcohol are required to achieve
when it puts the you in danger the effects originally produced by lower
Continuing to use, even when you know
l
doses (clear examples of this are found in
you have a physical or psychological alcohol-dependent individuals who may
problem that could have been caused or take daily doses sufficient to incapacitate
made worse by the substance or kill non-tolerant users)
Needing more of the substance to get the E. Progressive neglect of alternative
l
effect you want (tolerance) pleasures or interests because of alcohol
use, increased amount of time necessary
Development of withdrawal symptoms,
l
to obtain or take alcohol or to recover from
which can be relieved by taking more of
its effects
the substance.
F. Persisting with alcohol use despite clear
evidence of overtly harmful consequences
As per DSM-5cocaine use disorders are classified as mild, moderate and severe. As far
this document is concerned most of the studies are based on cocaine dependence/
abuse/use – hence cocaine use disorder is used to include problem use, abuse and
harmful use15.
3.1 Scope of the Guidelines
These guidelines are neither comprehensive nor definitive. Cocaine use in India is rare
but gradually in a transitional society like India it is being increasingly recognised as a
problem. Currently it is used by only high socio-economic status of the society. Hence
the treatment seeking is only restricted to private hospitals; hence large government
hospitals, where most of the Drug Abuse Monitoring System is carried out, often miss
them. This has led to very less research in this population. However, the growing
importance of cocaine cannot be denied in the aftermath of globalization and increased
availability. So we need guidelines and there is need to treat people suffering from
cocaine dependence. Hence we have to depend mainly on research carried out in
western setting. Indian psychiatrists and mental health professionals caring for patients
should consider the evidence base but not be limited by the recommendations made, as
patients are cared in a number of different settings in our country. In the present form the
guidelines are particularly applicable to De-addiction centres, and General hospital
psychiatric centres. In this article we are not going to discuss about evidence base for
management of dual diagnosis which requires a separate guidelines. Also this should
not be considered as comprehensive enough to accommodate all know

Cocaine
pharmacotherapy or behavioural interventions as around 60 medications have been

tried. Equally important are the psychotherapeutic interventions – these need to be
adapted to the Indian conditions for their best efficacy.
The guideline seeks to summarise the recent data available on major treatments
available for people with cocaine use disorder which might assist practitioners to ensure
minimum standards of care. Relevant literature was identified through a PubMed
literature search for publications related to this guideline. Searches were conducted;
using the keywords like “cocaine abuse OR cocaine dependence OR cocaine use” The
search yielded 35658 references till 20th Sep 2015. The search was restricted to human
studies, written in the English language, and had abstracts, of which there were 21,568
studies. Among them relevant original articles, reviews of recent past were considered.
Additionally, standard textbooks, bibliography of relevant articles and other guidelines
like APA, NICE, BAP, WHO guideline for treatment of cocaine use disorders were also
searched16,17. The Cochrane databases were also searched for relevant meta-analyses.
The summary of treatment recommendations is keyed according to the level of
evidences.
To maintain uniformity in standard and quality of guidelines, the Appraisal of
Guidelines for Research & Evaluation II (AGREE II) Instrument has been used in
preparing the guidelines. The strength of recommendation reflects not only the
evidence but also the importance of the study.
4. REVIEW OF TREATMENT MODALITIES
4.1 General Issues
While treating patients with cocaine use disorders several factors should be taken into
consideration. As cocaine dependence is a chronic relapsing and recurring condition,
patients will require a comprehensive, continuous care for prolonged period. An
integrated bio-psychosocial approach to care is needed to address several aspects of the
treatment. An active collaboration with the family (particularly in India unlike in
western countries) while planning and delivering treatment is required. Management of
the cocaine use disorders should be sensitive to the needs and empirically titrated to the
patient's response and progress. The main goal of treatment is to maintain abstinence
and if not possible then decrease the frequency and severity of relapses and maximize
functioning in between. The specific goal depends on the stage at which patient
presents.
4.2 Treatment Aims / Goals
The aims of treatment of cocaine dependence syndrome are:
Promote complete abstinence.
Stabilize acute medical (including cocaine intoxication/withdrawal) and psychiatric

conditions, as needed.
Increase motivation for recovery.
Initiate treatment for chronic medical and psychiatric conditions, as needed.
Enhance coping and relapse prevention skills.
Improve occupational functioning, social support and assist in integrating to society on
as needed basis.
Promote maintenance of recovery through ongoing participation in structured
treatment or self-help groups.
The goals of treatment vary according to time frame, across individual patients and can
be revised from time to time. It has been broadly divided into short term and long term
goals. The short goals are management of intoxication, management of withdrawal
symptoms, motivation enhancement, treatment of acute medical sequel and crisis
intervention. Long term treatment goals are relapse prevention, to maintain abstinence,
occupational rehabilitation, social reintegration, abstinent life style and improving the
quality of life of a person. This guideline will focus on the evidence available for the
management of intoxication, management of withdrawal symptoms, and management
of dependence. Goals of treatment should be set and agreed between the patient and
the clinician.
5. ASSESSMENT OF COCAINE USE DISORDERS
The assessment is very important as it forms the first point of contact and a thorough and
good assessment will help in diagnosing, establishing rapport, motivating the person
and in formulating the plan of the management.
5.1 Brief Overview
The assessment is very important as it forms the first point of contact and a thorough and
good assessment will help in diagnosing, establishing rapport, motivating the person
and in formulating the plan of the management. The goal of assessment also varies in
different phases of the treatment. During the first contact it is to establish rapport,
diagnosis and plan of management, and during intervention it is monitoring the
progress and assessing abstinence. The goal also depends on the context, motivation of
the client and cooperativeness of the client. If the client is uncooperative the aim of
assessment is to retain the client in the treatment. During this time the information can
be collected in pieces and information can be added when patient is co-operative.
5.2 Clinical History
A detailed assessment should include substance related factors such as age of initiation,
frequency, amount, tolerance, craving, withdrawal symptoms, salience, loss of control,
persistent despite harm, last dose, motivation, consequences of substance use (physical,
psychological, financial, family problems, vocational and legal), history of other
substance use, physical and psychiatric comorbidity if any, abstinence related factors
Cocaine
such as past abstinence, duration of abstinence, reasons for relapse, past treatments
(pharmacological or non-pharmacological or both), methods used for controlling
craving. It also includes history of high risk behaviours, presence of any externalizing
disorders, physical and psychiatric comorbidity, family history of substance abuse and
psychiatric illness, assessing social support, current living arrangements and reasons for
current visit.
5.3 Physical Examination
A thorough physical examination to assess for intoxication, withdrawal symptoms and
evidence of physical damage due to alcohol use or other substance use should be done.
Also a thorough mental status examination and psychopathology in case of co-morbid
psychiatric conditions should be done. Psychological or neuropsychological testing
can be done for some individuals with history of cognitive impairment.
5.4 Instruments
Scales provide ways to structurally assess the individuals with cocaine use disorders.
Some of the scales like ASSIST, Cocaine Selective Severity Assessment can be used to
make diagnosis and identify the intensity of withdrawal symptoms.
5.5 Investigations
Investigations are used to confirm the presence of the cocaine, assess the degree of the
physical damage and to confirm the presence of sexually transmitted disorders.
Investigations such as liver function test, hemogram, GGT, VDRL, HIV in high risk cases
can be used. Though not used routinely, in some cases, neuropsychological tests can be
used to assess the cognitive function particularly in cases with medical, psychiatric
complications or with co-morbid other substance use.
6. SHORT TERM MANAGEMENT
6.1 Management of Cocaine intoxication
Cocaine intoxication is commonly encountered in clinical settings particularly medical
emergency settings. Diagnosis of intoxication can be made according to the criteria set
up in ICD-10 or DSM-5. The clinical assessment should include general assessment as
described in 'assessment' with particular emphasis placed on physical status, mental
status, substance use history and associated consequences. If urine screens are available
they can be screened and noted in the clinical history. The acute effects of cocaine
intoxication generally subside with time and medications are needed for symptomatic
management. Specific pharmacological treatment is necessary when there is a history of
recent use of other substance use and with physical consequences (e.g., respiratory
depression, stroke, arrhythmias, etc.,). If mildly intoxicated general measures like
reassurance and maintenance in a safe and monitored environment do decrease
external stimulation and provide orientation if necessary. Adequate hydration and
nutrition should be provided. If patient is very anxious short acting low dose

benzodiazepines and if severely agitated low dose antipsychotics can be used to control
symptoms. While using benzodiazepines a close watch should be kept on respiratory
difficulty and while using antipsychotics a close watch should be kept for occurrence of
seizures and extrapyramidal symptoms. After the patient stabilizes then we need to
assess the patient comprehensively and also assess for withdrawal and further
management. The medical management of cocaine intoxication depending on the
organ involved has been given in several medical guidelines18,19.
6.2 Management of cocaine withdrawal:
Though cocaine withdrawal does not produce the severe symptoms as seen in alcohol
or heroin withdrawal and at one point of time its entity was debated, recent editions of
Diagnostic and Statistical Manual and International Classification of Diseases have
recognized it as a constellation of symptoms that occur after sudden cessation of
cocaine intake. Since cocaine has a relatively short half-life of 90 minutes hence
withdrawal symptoms may occur quite dramatically following the last dose particularly
in the intravenous route. Initial pioneering study on cocaine withdrawal was done by
Gawin and Klebel in 1980s. Using data from 30 out-patients they showed that there are
three distinct phases of cocaine withdrawal namely 'crash', 'withdrawal' and
'extinction'20. The phase one or 'the crash', developed rapidly following abrupt
cessation of heavy cocaine use and is characterised by acute dysphoria, irritability and
anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to
use. Phase two, 'withdrawal' is characterised by increasing craving to use, poor
concentration, some irritability and some lethargy, which persisted for up to 10 weeks.
Phase three, 'extinction', comprises intermittent craving to use in the context of external
cues. Despite the relative persistence of this model to the clinical application of cocaine
withdrawal results from several other studies have not supported this model and they
rather predict a gradual return to the basal levels21. The withdrawal state is diagnosed as
per DSM-V or ICD-10. The severity of cocaine withdrawal has been related to increased
craving and early drop-out.
Management of cocaine withdrawal requires constant monitoring of signs and
symptoms of withdrawal. The goals of the withdrawal are a) To relieve patient's
discomfort, prevent the occurrence of more serious symptoms, and forestall cumulative
effects that might worsen future withdrawal; b) To utilise the withdrawal treatment
opportunity to engage patients in long-term management.
There are no well-studied pharmacological agents to relieve symptoms of cocaine
withdrawal. The evidence base is for dopamine agonists like amantadine and
bromocriptine. Amantadine appears to primarily exert its therapeutic influence by
releasing dopamine and norepinephrine from neuronal storage sites that are depleted
by chronic cocaine dependence.22 Amantadine has been found to be effective in double
blind placebo controlled studies to relieve the withdrawal symptoms in few studies23.
One study has also showed that patients with more severe baseline withdrawal had

Cocaine
more improvement compared to lower baseline24. The dose range used in these studies
is from 100-400 mg/day. There is one negative placebo controlled study too23. Although
amantadine is found useful in cocaine withdrawal but more studies are needed to settle
its exact role. Thus the role for amantadine in cocaine withdrawal still remains unclear
except in cases of severe withdrawal.
Bromocriptine acts as a dopamine agonist that stimulates dopamine receptors.
Bromocriptine was found to be reducing cocaine withdrawal in few studies though
recent studies have not proved its efficacy. When compared with amantadine,
bromocriptine was associated with reduced tolerability and increased drop-out the dose
range used in these studies is 2.5mg to 10mg.26
Propronolol is another drug which has been used with mixed efficacy. 27 A recent trial
which evaluated the efficacy of amantadine (300mg/day), propranolol (100mg/day) and
their combination in cocaine dependent patients with severe cocaine withdrawal
symptoms showed that none of the treatments were significantly more effective than
placebo. Propranolol treatment was associated with better treatment retention and
higher rates of cocaine abstinence compared to placebo.28
Though some drugs have been used the strength of evidence is at best 'D' and needs
further research using well planned randomised controlled design.
7. LONG TERM MANAGEMENT OF COCAINE USE DISORDERS
Cocaine dependence syndrome like any other addictive disorders is a chronic illness
with lapses and relapses. Medications and psychosocial strategies are used for
promoting abstinence and preventing relapse in patients with cocaine dependence. All
the pharmacological agents used in cocaine use disorders have been studied along with
psychosocial interventions. Hence clinicians should use whichever psychosocial
approach they think beneficial or is available along with pharmacological agents.
7.1 Pharmacological Agents
The pharmacological agents used broadly belong to psychostimulants, antiepileptics,
disulfiram, antipsychotics and antidepressants class. The current guideline is based on
evidence obtained from developed country (particularly USA) as there is none from
India. There is little recent evidence for use of topiramate and modafinil for cocaine
dependence.
7.1.1 Topiramate
7.1.1.1 Mechanism of action:
It is a fructose-related monosaccharide that is approved for the treatment of narcolepsy
and epilepsy. Chronic cocaine use leads to malfunction of the GABAergic inhibitory
pathways relative to the glutaminergic excitatory pathways in the dopaminergic
excitatory pathway.29,30 Hence it may be helpful in cocaine dependence as it works
through a multitude of mechanisms namely augmentation of the GABAergic pathways

and inhibition of the glutaminergic kainite and AMPA receptors and also by blockade of
voltage gated sodium and calcium channels-hence it is suitable for treating chronically
low GABA signalling in cocaine users.
7.1.1.2 Dosage:
Dosage ranged from 200mg/day to 300mg/day in the clinical trials. The rate of dosage
increase is 50 mg per week.
7.1.1.3 Evidence base
Efficacy of topiramate as an anti-craving agent has been seen in human volunteers under
controlled conditions in the laboratory. A pilot study (n=40) showed that topiramate up
to 200mg reduced cocaine usage in a 8 week trial.31 In another open-label RCT which
was a feasibility study in Netherlands on crack cocaine users it has been shown that the
efficacy of topiramate as an add-on to cognitive behavioural therapy (CBT) in crack-
cocaine dependent patient was generally low.32 Although 82% of the patients in the
experimental group agreed to start topiramate treatment), only 14% took topiramate for
at least 11 of the 12-weeks. There are two double blind placebo controlled RCT. In one
study which involved 170 cocaine and alcohol dependent subjects for 13 weeks
duration after achieving a period of abstinence, subjects were randomized to
topiramate, 300 mg daily, or identical placebo capsules in addition to weekly individual
psychotherapy. It has been found that cocaine was not better than placebo in the
primary outcome measures namely self-reported alcohol and cocaine use, and thrice
weekly urine drug screens.33 In another study (n=142) it was seen that topiramate was
more efficacious than placebo at increasing the primary outcome namely weekly
proportion of cocaine non-use days as well as increasing the likelihood of urinary
cocaine-free weeks as well as decreasing craving and improving observer-rated global
functioning days34. So, overall, the evidence for topiramate in the treatment of cocaine
dependence is mixed.
7.1.1.4 Conclusion:
Hence it can be said that though topiramate is now an emerging treatment; however,
because of the contradictory findings it cannot be recommended as yet a first line
therapy.
7.1.2 Modafinil
7.1.2.1 Mechanism:
Modafinil is a stimulant which is approved for the treatment of narcolepsy and shift work
sleep disorder. Its proposed mechanism of action is by blocking the dopamine
transporter and thereby increasing dopamine concentration in the extracellular space of
11
nucleus accumbens. Hence, working as a mild stimulant it can reduce stimulant
withdrawal and also suppress cocaine craving. Its action is, however, distinct from other
stimulants and there are other mechanisms - modafinil's effects in the brain involve

Cocaine
hypocretin, histamine, epinephrine, γ-aminobutyric acid and glutamate35. Its actions on

glutaminergic pathways are important as it is opposite to that of alcohol and this may
have clinical relevance in patients of cocaine use disorder with co-morbid alcohol
dependence.
7.1.2.2 Dosage: 200-400mg per day.
7.1.2.3 Evidence base:
Modafinil was found to block the euphoria arising out of cocaine use in human
laboratory experiments and it has also been found to be medically safe when used along
with intravenous cocaine36,37. A double blind placebo controlled RCT of modafinil at
400 mg showed self-reported abstinence of over 8-12 weeks verified by twice weekly
urine benzoylecgonine tests compared to placebo38. Another 8-week, double blind,
placebo controlled clinical trial, involving 94 cocaine dependent subjects without co-
morbid alcohol dependence receiving 300 mg of modafinil or identical placebo daily,
along with weekly individual therapy, reported significant improvement in terms of
both the primary and secondary outcome measures39. There are few negative trials also.
In an eight-week randomized, double blind, placebo-controlled study of modafinil
treatment for cocaine dependence with patients (n=210), who were actively using
cocaine at baseline, were randomized to 8- weeks of modafinil (0 mg/day, 200 mg/day
or 400 mg/day) combined with once-weekly cognitive behavioural therapy, no
significant benefit was found for modafinil40. A large government-funded multisite study
done in 210 individuals reported that a 12 week trial did not show better efficacy for
modafinil in terms of the primary outcome that is weekly percentage of cocaine non-use
days41. Two secondary outcomes namely the maximum number of consecutive non-use
days for cocaine, and a reduction in craving showed significant effects. However, the
study also included patients with co-morbid alcohol dependence – hence when a
separate analysis was done for cocaine users without other substance use co-morbidity
there was increased efficacy for modafinil even in terms of the primary outcome.
Overall modafinil was quite well tolerated apart from minor adverse effects as reported
in some of the trials namely anxiety, insomnia and headache and there were no reports
of abuse in the trials conducted. Since modafinil is known to stimulate the DAT receptor
there have been apprehension regarding its abuse potential. However, given its
dopamine potentiating effects – caution should be maintained regarding its abuse
potentia42.
7.1.2.4 Conclusion:
Modafinil is emerging as a prospective medication for cocaine dependence without co-
morbid alcohol dependence though caution needs to be exercised in view of some
negative trials and also probable abuse potential.

7.1.3 Disulfiram
Disulfiram is being used in alcohol dependence for long time and its use in cocaine
dependence is of more recent onset. In cocaine dependence the proposed mechanism
of actions are at the level of monoamine neurotransmitters. Disulfiram has been shown
to chelate copper thereby inhibit dopamine beta hydroxylase resulting in excess of
dopamine and reduced norepinephrine. Disulfiram also inhibits carboxylesterase and
cholinesterase by unknown mechanisms43. This interferes with the metabolism of
cocaine, increasing plasma levels which may potentiate its cardiovascular effects
leading to adverse effects44.
7.1.3.2 Dosage:
62.5mg to 250mg.
Randomized clinical trials of disulfiram as a treatment for cocaine dependence have
been inconsistent. Most studies have found that treatment with disulfiram (250 mg/d)
decreases cocaine use though one well-controlled study found that treatment with
lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use significantly. A
Cochrane review included seven controlled studies that randomised a total of 492
participants to receive disulfiram, a placebo, no pharmacological treatment or
naltrexone in addition to psychosocial treatment. Disulfiram showed a trend toward
fewer dropouts from psychosocial treatment when compared to placebo (three trials) or
Naltrexone (three trials) but this was not statistically significant45.
7.1.3.4 Conclusion:
Disulfiram may be used in cocaine dependence though definite evidence is lacking
regarding its efficacy.
7.1.4 Stimulants
7.1.4.1 Mechanism of Action:
In cocaine dependence agonist substitution or replacement therapy has also been tried.
Here a similar but less harmful chemical with the intention of harm reduction as done in
opioid has been tried for cocaine dependence. The ideal drug which should be used for
replacement or substitution should have a similar mechanism of action and also there
should be suppression of craving, act for a longer time and should not be as strongly
reinforcing as the substance substituted for. Ideally a substituting agent should have a
similar mechanism of action, onset of action should be slower but it should be longer
acting. In fact preclinical animal studies and laboratory based studies show that the
behavioural and reinforcing effects of cocaine, amphetamine, methylphenidate are
similar46. Hence they can act as replacements.

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However, there are some neurobiological explanations also for example it has been
proposed that methylphenidate improves the neurocognitive functioning in cocaine
users who can therefore use it as a pre-requisite for psychosocial interventions.
The main drugs used are methylphenidate, amphetamine, modafinil, bupropion,
mazindol, methamphetamine and selegeline47. Modafinil has been described already
above.
7.1.4.2 Amphetamine
7.1.4.2.1 Mechanism of action:
Amphetamine acts as direct releasers of monoamines at the nerve terminals.
7.1.4.2.2 Dosage:
Dextro-amphetamine 15-30 mg
7.1.4.2.3 Evidence base:
Double blind RCT study have shown to decrease cocaine use though there were
contradictory result48,49. One trial has also been conducted with methamphetamine
sustained release and another pilot trial with lisdexamphetamine. The former showed
significant improvement whereas the latter showed non-significant decrease in use50,51.
These studies have only small number of cases and research is difficult with these drugs
as they are all controlled drugs46.
7.1.4.2.4 Conclusion: No evidence currently for using methamphetamine or
dextroamphetamine.
7.1.4.3.1 Methylphenidate (MPH):
MPH is currently used commonly for attention deficit hyperactive disorder (ADHD).
MPH as per literature was first used by Khantzian to decrease cocaine use52.
7.1.4.3.2 Dosage:
60 – 90 mg/day
7.1.4.3.3 Evidence Base:
There are several open label studies which have showed that MPH is useful and there
are equally good number of studies which have showed negative result53,54. Recently
few double blind placebo controlled studies which have showed that MPH is useful in
the fixed doses of up to 60mg/day. For heavy cocaine users more than 90mg have been
advised. However, only a very few studies have tested high dosage of MPH46. These
studies have several methodological problems- hence they are to be interpreted with
caution.
7.1.4.3.4 Conclusion:
At present due to inadequate evidence methylphenidate cannot be recommended for
long term treatment of cocaine dependence.

7.1.5 Anticonvulsants:
The 'seizure kindling' mechanism has also been hypothesized to be an explanation
for addictive disorder. Hence, almost all anticonvulsants ranging from carbamazepine,
tiagabine, gabapentin, lamotrigine, topiramate, valproate, phenobarbital, phenytoin
and vigabatrin have been used56, 57,58,59, 60,61. These anticonvulsants potentiate the GABA-
ergic mechanisms which may lead to decrease of dopaminergic tone of the nucleus
accumbens thereby decreasing cocaine re-instatement and cocaine self-
administration62. Topiramate as an anticonvulsant has shown some encouraging results
so it has been discussed separately.
A recent Cochrane review compared anticonvulsants with placebo and found no
significant differences for any of the primary outcomes measures namely drop-out, use
of cocaine by urinalysis or self-report, adverse effects and secondary outcomes namely
compliance, craving, severity of dependence, depression and anxiety when
anticonvulsants were compared with placebo63.
7.1.6 Antipsychotics:
Acute cocaine use leads to an increase in dopamine secretion in certain brain areas
whereas chronic cocaine use leads to reduced dopamine tone. So anti-psychotics have
not been favoured much because of the proposition that they would decrease the
dopamine tone further and lead to more hedonic deficiency and subsequently further
increase in cocaine intake64. However, with the advent of the atypical anti-psychotics
there has been renewed interest in this topic as they are acting not only on the
dopaminergic pathways but also on the serotonergic pathways. Most of the older
studies have been conducted with haloperidol whereas the newer studies have been
conducted with olanzapine, risperidone, quetiapine and aripriprazole and have been
used in cocaine dependence in association with schizophrenia or bipolar
illness65,66,67,68,69,70.
7.1.6.2 Dosage:
Olanzapine 5 - 10mg/day; Risperidone: 1mg to 4mg/day; Haloperidol: 4 and 10mg/day;
Quetiapine: 400mg/day
In few studies risperidone was effective in reducing the number of drop-outs and
effective in treatment retention. Haloperidol and olanzapine were each found to reduce
craving with respect to placebo though there were contradictory findings in other
studies and the sample size was too small to be conclusive65,69. A cochrane review
regarding the usefulness of anti-psychotics in the treatment of cocaine use disorder
Cocaine
which included seven studies (N=293) found no significant differences for any of the
efficacy measures comparing antipsychotics like haloperidol, risperidone and
olanzapine with placebo. In a recent meta-analysis which included ten studies
(risperidone=5, olanzapine=3, reserpine=2; N=562) with primary cocaine
dependence concluded that antipsychotics did not differ from placebo with regard to
cocaine use days and lack of cocaine abstinence, severity of addiction, cocaine craving,
Clinical Global Impressions-Severity of Illness (CGI-S) scores, depression, anxiety,
compliance, all-cause discontinuation, and several side effects. However,
antipsychotics caused more intolerability-related discontinuation than placebo. For
quetiapine initial open-label studies showed efficacy when used at a dosage of
400mg/day in suppressing cocaine use and craving in non-psychotic patients. There is
a double-blind, randomized, placebo-controlled study for 12-week, involving cocaine
dependence syndrome with quetiapine (N=31) which showed that there is no
significant benefit of quetiapine compared to placebo (N=31) on self-report of cocaine
use and money spent on cocaine as well as urine drug screens73.
Methodology-wise most of studies had small sample sizes and measured treatment
retention or drop-out as the main outcome measures though some studies measured
craving as a secondary outcome measure. Also some of the studies had co-morbid
heroin dependence and were maintained on methadone .
7.1.6.4 Conclusion:
Currently there is inadequate evidence to suggest the use of anti-psychotics in non-
psychotic patients with cocaine use disorder.
7.1.5 Antidepressants:
Acute cocaine use leads to increase of monoamines namely dopamine, serotonin and
nor-epinephrine. However, with chronic use there is deficiency of the mono-amines –
so use of anti-depressants may lead to stabilization of the brain mono-amine levels and
hence amelioration of the short and long-term symptoms related to cocaine abstinence.
Also neuroimaging studies have shown that the areas of the brain activated are often
common between cocaine use disorder and mood disorder – this is probably best
illustrated by the mood symptoms during cocaine withdrawal. The most common anti-
depressants which have been studied are desipramine, fluoxetine and bupropion74,75.
Other antidepressants which have been studied are nefazodone, ritanserin, buspirone,
gepirone, paroxetine, citalopram, venlafaxine, selegiline, tryptophan, sertraline, and
imipramine76.
7.1.5.2 Dosage:
Desipramine: 75 -300mg/day; Fluoxetine: 20-60mg/day; Bupropion: 300mg/day


A Cochrane review included 37 studies (N=3551) concluded that there were
significant heterogeneity in the studies in terms of design, instruments used, services
and treatment delivered. Positive results obtained by antidepressants on mood-related
outcomes are consistent with the primary effect of antidepressants. They do not seem to
be associated with any effect on dropouts from treatment, cocaine use or side effects,
which are direct indicators of cocaine abuse and dependence77. A recent systematic
review compared antidepressants with dopamine agonists and showed that
antidepressants were better for abstinence, based on two studies (N=44)78. The strength
of the evidence is very low. Both the reviews mentioned that current evidence does not
support the use of antidepressants.
7.1.6 Dopamine agonists:
It has been described already in management of withdrawal state. The drugs commonly
used are amantadine, bromocriptine, L-dopa/Carbidopa, pergolide, cabergoline,
hydergine, and pramipexole.
7.1.6.2 Dose:
Amantadine 100-400mg/day; Bromocriptine=2.5-10mg/day; L-dopa/Carbidopa=75-
800mg/day/100-200mg/day; pergolide=0.1-0.5mg/day; Cabergolinehydergine =
0.5mg/week; and Pramipexole = 3mg/week.
7.1.6.2 Evidence Base:
A recent systematic review of 24 studies (N=2147 participants) concluded that current
evidence from RCTs does not support the use of dopamine agonists for treating cocaine
use78.
7.1.6.3 Conclusion:
At best currently there is no definite evidence for their efficacy.
7.1.7 Cocaine Vaccine
Cocaine vaccine is a newer approach. Here vaccinated individuals produce antibodies
which bind to drug molecules and inhibit the passage across the blood brain barrier and
reducing the subjective effects79.
7.1.7.2 Evidence Base: The Phase 1 and Phase 2 studies of cocaine vaccine have
showed significant decrease in cocaine use in patients who have attained sufficient
level of anti-cocaine antibodies80. The effect of anti-cocaine antibodies dropped off
rapidly and its efficacy decreased after short time. A recent 6 site 24 week phase III
randomized double blind placebo controlled study of around 300 patients at 16 weeks
reported injection site reactions of induration and tenderness and around 29 serious

Cocaine
adverse effects which did not lead to serious consequences or death. They concluded
that the vaccine was safe. At 16 weeks there was no difference in abstinence rate as
measured by cocaine positive urine rates with placebo81. Addressing the anti-cocaine
antibodies level dropping further will have a role in anti-cocaine vaccine efficacy.
Conclusion:
Currently there is not much strong evidence to recommend the use of cocaine vaccine.
7.1.8 Other medications:
Other medications that have been used are ondansetron, baclofen, have found to be
useful but need further RCTs to prove their efficacy82,83.
7.1.9.1 Combinations of medications:
Studies have been done using combination of pharmacotherapy. The combinations
have been used as per the tentative underlying neurobiological basis of the
medications.
7.1.9.2 Dosage:
Medications used have been a combination of naltrexone (50 mg) and isradipine(10
mg), bromocriptine and desipramine (200 mg/day), I-tryptophan (1 g/day) and I-tyrosine
(1 g/day), amantadine (300mg/d) and propranolol (100mg/d), disulfiram (250
mg/day)and Naltrexone (100 mg/day) , metyrapone (500 mg/day) and oxazepam (20
mg/day) mixed amphetamine salts (60mg/day) and topiramate (300 mg/day) combined
d-amphetamine(60mg/d) and modafinil, (400mg/day)84,85,28,86,87,88,89.
Among the double blind randomized controlled trials done with the above
combination of medications most are negative studies except the study with
amphetamine salts and topiramate (3 months abstinence).90
7.1.9.4 Conclusion:
There is need for well conducted studies to recommend the use of combinations in
cocaine dependence.
7.2 Psychosocial Treatment
As we have seen none of the pharmacotherapies have very good efficacy – hence
psychosocial interventions take an important role in the treatment of cocaine
dependence/ problem. A variety of psychosocial strategies have been used in cocaine
dependence. The different approaches that have been taken for the treatment are
behavioural approaches like contingency management, comprehensive strategies like
community reinforcement approach, cognitive behaviour treatment, twelve step
oriented treatment, self-help group and newer generation psychotherapies like
mindfulness based therapy.

7.2.1 Behavioural approaches:

It is based on the conventional behavioural paradigm. It recognized the strong natural
rewarding effects of cocaine which allow it to be naturally re-enforcing. So in
behavioural paradigm alternative rewards are created and patients tend to preferentially
select them on producing drug free urine samples. This is particularly used for patients
with co-morbid opioid dependence. In most of the studies patients receive reward at an
intermittent schedule.
7.2.1.1 The most thoroughly studied method for treating cocaine dependence is the
‘fish-bowl’ approach where cocaine dependent patients are given the option to submit
urine drug free samples and contingent upon it they are given the opportunity to draw
for prizes or vouchers that vary in amount91. Beneficial results of such an approach have
been demonstrated in patients with co-morbid cocaine and opioid use disorder on
methadone as well as in the community. Also benefit has been shown in other patient
populations like those with anti-social personality disorder, pregnant women and those
exposed to tuberculosis. Overall behavioural therapies are very important in treatment
of cocaine dependence as concluded by a meta-analysis which showed its effect size to
be about 0.692.
7.2.1.2 In the community based reinforcement approach (CRA) apart from
reinforcement by reward there are other components like providing skills training (such
as problems with drug refusal, problem solving or assertiveness) to minimise drug use,
improving family relations, providing vocational and employment counselling,
assisting with developing new recreational activities and social networks, and
monitoring disulfiram therapy for those who abused alcohol. This concept of
comprehensive care has been given by the matrix model- which gives an opportunity
for the patients to develop themselves in lines with the CRA. It has shown promise in the
maintenance of abstinence. In a study in 40 ambulatory cocaine-dependent adults
were randomly assigned to behavioural treatment with or without an added incentive
program - 75% of patients in the group with vouchers completed 24 weeks of treatment
versus 40% in the group without vouchers - incentives delivered contingent on
submitting cocaine-free urine specimens significantly improve treatment outcome93.
Addition of voucher based interventions have specific advantages – in other study it has
been shown that combining CRA with vouchers had therapeutic effects on substance
abuse and psychosocial functioning during treatment and post-treatment follow-up in
cocaine-dependent outpatients, although effects on cocaine use appear to be limited to
the treatment period94.
7.2.2 Cognitive behavioural therapy (CBT): It is a combination of cognitive and
behavioural approaches – it focuses particularly on the antecedents, behaviours and
consequences of relapse in a structured manner. It is a goal-directed, flexible, structured
therapy that focuses more on the maladaptive coping skills which have led to the
relapse. It helps to identify the triggers of relapse and deal with it accordingly. It consists

Cocaine
of multiple sessions focussing on social skills and involvement of the patient in the form
of home-work assignments. Studies have shown that CBT is effective95.Others studies
with larger sample sizes, have not found it to be uniquely effective. Studying the
methodology of the individual studies it may be concluded that CBT was more effective
when there have been a longer duration of use and that for shorter duration it may not be
more effective96.
Among the important therapies namely contingency management, CRA and CBT it is
worthwhile to compare amongst them. The Cochrane review observed that although
the CBT seemed to be a promising however in the short term contingency based
approaches appear to be more important. However, in the longer run CBT has more
efficacy, though such studies are difficult, as was concluded by the Cochrane review
where they highlighted the significant heterogeneity of the studies as well as the
therapist specific issues97. This has led to the development of computer based CBT
which can be used in longer term and which also holds promise in terms of efficacy98.
7.2.3 Twelve step facilitation program (TSF): It is based on the principles of twelve step
program whereby spiritual elements are included in the self-help group intervention.
Here the patients undergo a fellowship where under the guidance of a 'sponsor' they
take a pledge whereby he surrenders to the Almighty and tends to discuss all causes of
relapse and other hindrances faced in day to day dealing with substances. Similar
programmes which deals with substances namely the alcohol anonymous, narcotics
anonymous. Now evidence is also accruing favouring TSF. A randomized, placebo-
controlled, double blind medication, with 4 treatment conditions: disulfiram plus TSF,
disulfiram plus standard counseling only, placebo plus TSF, and placebo plus standard
counseling in the context of a community-based methadone maintenance program on
112 participants showed that assignment to TSF was associated with less cocaine use
throughout treatment and a higher number of cocaine-negative urines. Hence 12 steps
therapy appears to be of benefit to methadone maintaining patients using cocaine99.
7.2.4 Motivational enhancement therapy (MET): This intervention is based upon
Rogerian principles. MET is a client oriented, flexible, empathetic, non-judgemental
approach which helps in motivational enhancement. Though has been an underlying
principle in most of interviewing in substance use disorder yet structured intervention
has also been done. Two sessions of motivational interventions showed that patients
with poor coping skills decrease cocaine use irrespective of their poor motivation100.
Another study using same design did not find any benefit – hence MET may not be
efficacious in all scenarios though it needs to be an essential component of client
interactions100.
7.2.5 Other psychotherapeutic approaches: Other newer psychotherapeutic
approaches have been tried like “third wave” behavioural therapies, including
Acceptance and Commitment Therapy (ACT), Dialectical Behaviour Therapy (DBT),
Mindfulness-Based Stress Reduction (MBSR) and Transcendental Meditation (TM).

These have not been empirically validated though holds promise in future102.
7.2.6 Conclusion: There are no data supporting a single treatment approach that is able
to account for the multidimensional facets of addiction patterns and to significantly
yield better outcomes to resolve the chronic, relapsing nature of addiction, with all its
correlates and consequences. However, contingency management, community based
reinforcement approaches and CBT have the highest efficacy in RCTs as per current
evidence available.
7.3 Combined psychosocial and pharmacological management:
All the pharmacological agents used in cocaine use disorders have been studied along
with psychosocial interventions. Many of the RCTs have given positive results 92,31,103,104
and a few studies have given negative results75,54. Hence clinicians should use
whichever psychosocial approach they think beneficial or is available along with
pharmacological agents (A).
8.0 SPECIAL POPULATIONS
8.1 Pregnancy
A fallout of the 'cocaine epidemic' in western countries has been use of cocaine in
pregnant mothers. Though initially it was reported from United States later it came to be
reported from other countries including Europe. The epidemiological burden is
illustrated by the fact that in a recent study of over 3,000 neonates – although 11% of the
women reported using illicit drugs during pregnancy, 31% of the infants meconium
tested positive for cocaine alone2. Apart from the direct effects of cocaine on the in utero
fetus, other factors may also be responsible for the adverse outcome namely poor
nutrition and poor antenatal care. A recent meta-analysis found that prenatal cocaine
exposure is significantly associated with preterm birth, low birth weight, and small for
gestational age infants105. The long-term effects of prenatal cocaine exposure on
cognitive, motor, and language development have been inconsistent106. This
inconsistency is likely related to the confounding effects of the postnatal environment,
including dysfunctional parenting and unstable, chaotic home environments, and
frequent poly-substance use in the mother107. Till date there are no published reports of
cocaine related effects in the offsprings of cocaine using mothers from India.
8.1.1 Evidence base: Pregnancy itself is a great motivating force for women to quit and it
was found that among pregnant women using cocaine before pregnancy, 73% were
abstinent during pregnancy108. Most evidence in the treatment of cocaine using pregnant
mothers is in the use of CBT, 12 step process and contingency management (CM). In a
recent randomized trial comparing CM to community reinforcement approach and 12-
step facilitation, CM was associated with significantly greater duration of cocaine
abstinence, higher proportion of cocaine-negative urine tests and higher proportion of
documented abstinence across the study period 109. Pharmacological treatments have

Cocaine
not proved to be effective except the fact that a recent preliminary RCT with micronized
progesterone have found some efficacy in achieving abstinence in the post-partum
period110.
8.1.2 Conclusion:
Cocaine use in the pregnant women is through psychosocial interventions particularly
contingency management.
8.2 Attention Deficit Hyperactivity Disorder
In the general population, the prevalence of adult ADHD is 4.4%, while in individuals
with a substance use disorder, ADHD co-occurs at a rate of 10.8% with some studies
showing a prevalence of up to 30%111. The reason of increased cocaine use in the
ADHD population due to relief of depressive symptoms and anxiety arising out of the
illness. Hence self-medication hypothesis by EJ Khantzian has been propounded to be
the most important in establishing this co-morbidity. So use of stimulants as treatment is
a usual choice in this population apart from other medications like bupropion46.
8.2.1 Evidence base:
Methylphenidate (MPH) is one of the most commonly used stimulant in ADHD with co-
morbid cocaine use disorder. Among the three RCTs which have used, MPH in one
study showed some efficacy with decreased intake of cocaine – however, that study was
characterised by increased drop-out rate112. Also bupropion was not found to be more
efficacious when compared to placebo in an RCT. Stimulant therapy of ADHD in
childhood is associated with a reduction in the risk for subsequent drug and alcohol use
disorders. However, caution needs to be maintained about the abusive potential of
stimulants in this sub-group.
8.2.2 Conclusion:
At present there is no efficacy of any particular medication particularly stimulants
(methylphenidate) in cocaine dependence with ADHD.
9. RECOMMENDATIONS
9.1 Some issues to be considered before arriving at recommendations
l The proposed guideline is based on evidence obtained from developed country
(particularly USA) and none from India.
l Manifestations of cocaine intoxication and withdrawal are non specific and are
mostly self- limiting.
l Psychosocial interventions have reasonable evidence base and are recommended for
cocaine use disorders.

9.2 Recommendations
9.2.1 Management of Intoxication and withdrawal
There is no convincing evidence supporting the use of pharmacological treatment for
cocaine use disorder.
9.2.2 Management of cocaine dependence
Psychosocial treatments are the mainstay of treatment - contingency management,
community based reinforcement approaches and CBT have the highest efficacy. Other
therapies like MET, mindfulness based therapies needs further research.
Evidence for drug treatment is still preliminary – pharmacological treatment should be
used in combination with psychosocial therapies (A). Modafinil and topiramate are
emerging as prospective medications though currently evidence is not unequivocal and
contradictory evidences exist (C). Currently disulfiram, dopamine agonists,
antidepressants, anticonvulsants (except topiramate), psychostimulants, neither any
combination of these medications are recommended. Cocaine vaccine has been found
to be safe and shown promising results in Phase 1 & 2 research but not so promising
response in Phase 3.
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AMPHETAMINE-TYPE STIMULANTS (ATS)
Atul Ambekar
Shrigopal Goyal
On behalf of
2016
Amphetamine-type Stimulants (ATS)
CONTENTS
Executive Summary
1. Introduction
1.1 History
1.2 Epidemiology
1.2.1 Global
1.2.2 Asia
1.2.3 India
1.3 Neuropharmacology
2. Who uses Amphetamine/Methamphetamine
2.1 Who are more prone? Population group at-risk of ATS use
3. Amphetamine use Disorders
3.1 Dependence
3.2 Routes of amphetamine administration and pattern of amphetamine use
3.3 Effects of ATS
3.3.1 Acute Effects
3.3.2 Consequences of amphetamine use
3.3.3 Health consequences of amphetamine use
3.4 Hazards-Psychological
3.4.1 Paranoid psychosis
3.4.2 Depression
3.5 Amphetamine withdrawal
3.6 Use during pregnancy and perinatal period
3.7 Death among ATS users
3.8 Consequences of amphetamine use in the context of polydrug use
4. Management
4.1 Amphetamine Psychosis
4.2 Treatment of ATS withdrawal
4.3 Treatment of amphetamine use disorders
4.3.1 Pharmacological treatment

4.3.1.1 Antagonist strategies

4.3.1.1.1 Naltrexone
4.3.1.1.2 Serotonin Dopamine antagonist
4.3.1.1.3 Dopamine partial agonist
4.3.1.2 Agonist strategies
4.3.1.2.1 Dexamphetamine
4.3.1.2.2 Methylphenidate
4.3.1.2.3 Modafinil
4.3.1.2.4 Bupropion
4.4.1.3 Other treatment strategies
4.3.1.3.1 Serotonergic medications
4.3.1.3.2 5-HT3 antagonist (Ondansetron)
4.3.1.3.3 Mirtazapine
4.3.1.3.4 GABAergic agents
4.3.1.3.5 N-acetyl cysteine
4.4 Psychosocial treatment and treatment approaches
4.4.1 Interventions in the community and in primary health- care setting
4.4.2 Psychosocial treatment
4.4.3 Various type of Psychosocial treatment
5. Conclusion

EXECUTIVE SUMMARY
Amphetamine-type stimulants “(ATS)” or 'psychostimulants' are synthetic drugs that
excite or speed up the nervous system and produce effects similar to adrenaline. They
are highly euphoriogenic and consequently have a moderate degree of addictive
potential. Use of these substances is associated with a wide variety of physical,
psychological and social harms. Their use is growing in many parts of the world. In
India, though the use remains low as of now, there is recent evidence that ATS use may
be spreading in various parts of the country and hence clinicians need to be aware of
management of ATS use disorders.
For management of acute amphetamine psychosis, dopamine antagonists or 'anti-
psychotics' like chlorpromazine or haloperidol are indicated. The use of ascorbic acid
can accelerate the renal elimination of amphetamines.
ATS withdrawal is generally not medically hazardous though it can be associated with
depression. No medication has been demonstrated to be effective in alleviating
amphetamine withdrawal, but some medications may be useful. Antidepressants have
been used for withdrawal-induced depression with some benefit. Short-term use of
benzodiazepines (diazepam 5 to 10mg QID SOS) and antipsychotics (olanzapine 2.5-
5mg BD SOS) for control of irritability and agitation can be helpful.
The evidence-base for the treatment of ATS dependence is rather limited. The evidence
shows that various treatment agent like naltrexone, risperidone, modafinil, serotonin
reuptake inhibitor, bupropion have been tried but demonstrate very limited benefits for
amphetamine dependence. There are as yet no approved pharmacological treatments
for ATS users which are based upon the philosophy and principles of substitution
treatment (such as methadone or buprenorphine for opioid dependence). Maintenance
on prescribed amphetamines has been demonstrated to reduce the use of street
amphetamines.
Among psycho-social interventions, an eclectic “stepped-care approach” has been
developed which aims to provide individualized, evidence-based and voluntary
treatment.The services provided under the heading of “stepped care” include
community-based prevention and health promotion, creating awareness that there are
help/treatment options for ATS users, self-help groups, brief interventions of
motivational interviewing and cognitive–behavioural therapy (e.g. one to four
sessions), intensive individual counselling, detoxification and withdrawal services,
crisis interventions and emergency care, as well as long term rehabilitation and
reintegration services. Cognitive–behavioural therapy applied in a stepped-care
approach is the treatment of best practice for ATS use.
Clearly, more research is needed in this area to expand the evidence-base globally, as
well as in our country.

1. INTRODUCTION
Amphetamine-type stimulants“(ATS)”refer to a family of synthetic drugs that are
chemically related to the parent compound amphetamine (phenylisopropylamine).1
Also referred to as 'psychostimulants', they excite or speed up the nervous system and
produce effects similar to adrenaline. They are distinguishable from 'botanical'
psychoactive drugs (e.g., heroin, cocaine, cannabis), which are derived from plants.2
Amphetamines act as central nervous system stimulants, which increase synaptic
concentrations of monoamine neurotransmitters in the brain, namely, dopamine,
serotonin and noradrenaline. 3 The ATS group includes amphetamine,
methamphetamine and methcathinone, fenetylline, ephedrine, pseudoephedrine,
methylphenidate and MDMA or 'Ecstasy' – an amphetamine-type derivative with
hallucinogenic properties.4
The type and form of ATS manufactured vary across regions. For example, in East and
South-East Asia, manufacture of methamphetamine is primarily in tablet form ('yaba')
and high purity crystalline form ('ice'). Chemical precursors are necessary for the
synthesis of amphetamine-type stimulants (ATS), and these chemicals commonly fall
under international control. Their seizures are typically reported to the International
Narcotics Control Board (INCB) and it provides some indications about trends in
clandestine manufacturing. Ephedrine and pseudo ephedrine are precursor chemical
for methamphetamine. phenyl-2-propoanone (P-2-P), Phenyl acetic acid and
norephedrine are precursor chemical for both amphetamine and methamphetamine.5
Table 1 Common types of ATS5
Drug Common Name Forms Method of

administration
Amphetamine Speed, Whiz, Uppers, White, yellow, Pink or Oral, intranasal,
goey, dexies, pepe pills brown powder, paste injection, anal
Dexamphetamine Dexies, D-amp, dex White, round tablets Oral, intranasal,
(marking 'D5') injection, anal
Methylamphetamine Meth, speed, whiz, fast, White, yellow or brown Oral, intranasal,
('cut' or diluted formof uppers, goey, louee, powder, paste, tablets injection, anal
Methylamphetamine LouReed, etc. or a red liquid
hydrochloride salt)
Methylamphetamine Small crystal particle Crystalline- resembles Smoking,
hydrochloride size known as 'crystal'- crushed ice, particle intranasal,
(crystalline form - larger particle sizes size variable Injection
known as 'ice'; other
'uncut', undiluted)
terms include meth,
d?meth, glass, crystal,
batu, shabu (from the
Philippines)

Drug Common Name Forms Method of

administration
3,4-methylenedioxy- XTC, X, ecstasy, Adam, Tablet, powder, capsule, Oral, intranasal,
methamphetamine M&M, eccy, E, go, geltab (rare) smoking,
(MDMA) Scooby snacks, hug, injecting
beans
3,4-methylenedioxy- Eve Tablet Oral
ethylamphetamine
(MDEA)
N-methyl-1- Eve Tablet Oral

(1,3-benzodioxol-5-yl)
-2-butanamine
(MBDB)
The use of ATS is a global and growing phenomenon and in recent years, there has been
a pronounced increase in the production and use of ATS worldwide. Over the past
decade, use of amphetamine-type stimulants (ATS) has infiltrated its way into the
mainstream culture in certain countries. Younger people in particular seem to possess a
skewed sense of safety about ATS believing rather erroneously that these substances are
safe and benign. Meanwhile, ATS are posing a serious threat to the health, social and
economic fabric of families, communities and nations.
In many countries, the problem of ATS is relatively new, but quickly growing and is
unlikely to be controlled soon. Though the geographical spread is widening, the
awareness is limited and unfortunately there is a lack of integrated and consistent
responses.
The market for amphetamine-type stimulants (ATS) in the Asia and the Pacific region has
continued to grow in recent years, which is evident through recent seizures of
methamphetamine in pill and crystalline forms in most countries in East and Southeast
Asia. Illicit methamphetamine manufacture continued to spread throughout the region
and new markets emerged for a variety of other synthetic substances.6,7
1.1 History
The earlier documentation of use of amphetamine was found in China, where the ma
huang plant (Ephedra vulgaris) has been used to treat people with asthma.8This plant
contains ephedrine which was first produced by chemical synthesis in 1887 in
Germany.8 Subsequently, amphetamine came into medical and recreational use in the
1920s primarily for the treatment of colds and asthma. Methamphetamine, more potent
and easier to make than amphetamine, was discovered in Japan in 1919.9 The
crystalline powder was soluble in water, making it easy to inject. During the World War-

II and the Vietnam War methamphetamine was widely used by the armed forces to
increase alertness, confidence, feelings of increased strength and to suppress appetite.
In the United States in the 1950s, legally manufactured tablets of
bothdextroamphetamine (Dexedrine) and methamphetamine (Methedrine) were used
by college students, truck drivers, and athletes. By the 1960s the market in
methamphetamine had changed from being predominantly licit to illicit. This was
followed by the synthesis, manufacture and distribution of methamphetamine by
'motor cycle' and other criminal gangs in United States.9 Subsequently, they were
widely prescribed for weight control and treatment of attention deficit disorders.
However, since the 1970s, amphetamines have been manufactured in clandestine
laboratories and increasingly used as recreational drugs. Because of their high potential
for abuse, amphetamines became a Schedule II controlled drug following the 1971
Convention on Psychotropic Substances.4
1.2 Epidemiology
1.2.1 Global
In 2009–10, it was estimated that between 13.7 and 52.9 million people used
substances belonging to the amphetamines group at least once in the preceding year.
Data for East and South-East Asia suggest that between 4.4 and 37.9 million people have
used amphetamines in the past year, no estimates were available for South
Asia.10According to the world drug report, 2012 between 2008–2010, about 1.3% of
adults worldwide reported use of amphetamine type stimulants (ATS) involving
compounds that range from amphetamine to an array of amphetamine analogues, but
exclude 3,4-methylenedioxy-N-methylamphetamine or 'ecstasy.11A retrospective audit
of patients admitted between 2008 to 2013 at Albany Health Campus, western Australia
was found One hundred and fifty two ATS-related hospital episodes were identified
during the study period, 55% male and 45% female, with an age range from 16 to 50.12
The ATS market continues to evolve and grow. Globally, it remains the second most
widely used illicit drug after cannabis. In 2012, the World Customs Organization
reported an increase in border detections of ATS in North America, Western Europe and
the Middle East, with large quantities also detected in the Asia-Pacific region. During
2012, customs agencies reported a global increase in the number and weight of
methylamphetamine and MDMA detections. The largest methylamphetamine border
detections by weight were reported by customs agencies in Asia-Pacific, Western
Europe and North America.13
Iran is a growing source of methylamphetamine destined for both domestic and
international markets. Iran-based methylamphetamine trafficking networks have
become leading domestic market suppliers, in addition to supplying user markets across
the Middle East and Asia-Pacific region. The Bureau for International Narcotics and Law

Enforcement Affairs (BINLEA) reported that while Iranian seizures of opium and heroin
have remained stable, seizures of methylamphetamine are increasing, with 2012
figures reportedly increasing eleven-fold from 2008 to 2011.14 North America remains
both a transit and a source region for methylamphetamine. Canada is source for
methamphetamine and having many laboratories for production (Criger 2013).15
Mexico remains the primary source for methylamphetamine in the United States of
America (US), with media reporting indicating that more than 80 per cent of
themethylamphetamine seized in the US is manufactured in Mexico.16
Since 2010, however, surging ATS seizures point to a rapid expansion of the global
market, with total ATS seizures rising by more than 80 per cent to more than 135 tons in
2012. The increase of ATS seizures is primarily attributable to the growing amount of
global methamphetamine seizures, which have more than doubled over the same
period, reaching 107 tons in 2012. The growing importance of methamphetamine is a
new feature of the global ATS market. The high level of global methamphetamine
seizures in recent years has been primarily due to the rise of seizures in East and South-
East Asia and North America.17
1.2.2 ASIA
UNODC (2010) estimated that up to 20.7 million individuals in Asia and pacific region
used ATS in the past one year.18
Methamphetamine continues to dominate the ATS market in East and South-East Asia,
Oceania and the Pacific. ATS seizures in the region have annually increased from about
13 tons in 2008 to just under 40 tons in 2012. The rapid rise of ATS seizures over the
years is primarily attributable to the increase of methamphetamine seizures which
about tripled from less than 12 tons in 2008 to 36 tons in 2012.17,18
Review conducted in china based on the literature identified from searches of the China
national knowledge infrastructure (1979-2013), PubMed databases, hand-picked
references, and online references with emphasis on epidemiology, treatment and
traditional Chinese medicine. The epidemiological trends of ATS in China have led to its
being 2.2 times the rate of morphine abuse and second only to marijuana abuse.19
1.2.3 India
In general, ATS use has remained very low in India, compared to other illicit drugs. In
India, the extent, pattern and consequences of ATS use has not been studied. Over the
last few years, laboratories producing amphetamine-group substances have been
unearthed by law enforcement agencies from several parts of the country. India along
with China is the most frequently mentioned source country of seized illicit shipments
of ephedrine and pseudoephedrine which can be used to manufacture ATS. Anecdotal
reports and clinical data indicate the emergence of use of these substances in several
parts of the country.

However, National household survey (NHS) reported the prevalence of ever use of ATS
to be 0.03% Current use according to DAMS (National Survey) was 0.2%. Though,
Current use according to RAS (National Survey) was nil but in the thematic “Border
study” (as a part of National Survey),some ATS userswere detected.20 More recently
UNODC has commissioned a study on ATS use in India. This study was conducted in
the five states of Manipur, Mizoram, Punjab, Tamil Nadu and West Bengal, in India. The
study also assessed the adverse health consequences related to the use of ATS. The
findings of the study revealed that methamphetamine pills and powder were the most
commonly used forms of ATS. Most users were in their early twenties. The
usersreported a general feeling of euphoria and happiness, making it very attractive and
deeply desirable to consume. Nearly half of the participants of the study were found to
be dependent users and a quarter of them reported to have experienced mental
problems after ATS use including paranoia, hallucinations, depression and panic
attacks. The study also established a link between ATS use and crime, with 18 percent of
the participants confirming that they had been apprehended by the police after ATS use.
Study found 55 percent were ecstasy ever user, methamphetamine pills were ever used
by 42 percent of the respondents followed by methamphetamine powder (36 percent)
and amphetamines (35 percent) (UNODC,2015)21 Ecstasy was reported to be last used
in the past one month by 13.1 percent amphetamine by 8.2 percent. Among reasons for
initiation of ATS, more than half (57%) reported curiosity followed by peer influence
(17%). While citing reasons for their current use 30.8 percent reported, “to be more
energetic”.21
Thus, it is clear that ATS use though is low in India at present, in the coming years, the
clinicians are likely to encounter more cases affected by ATS use disorders and hence, it
is imperative for the clinicians to remain prepared to deal with this newer clinical and
public health problem. 22
1.3 Neuropharmacology
Amphetamines are sympathomimetic central stimulants. Their pharmacological action
is exerted indirectly by sustaining high levels of catecholamine in the synaptic cleft and
directly by binding to the postsynaptic adrenergic receptors. It acts as indirect
catecholamine agonist and releases serotonin and also blocks reuptake of dopamine.
Amphetamine undergoes extensive renal excretion and significant amounts are present
in urine as the unchanged parent drug. The concentration of amphetamine in urine is
about 200 times greater than the concentration in blood. Other factors could impact on
the urine-blood amphetamine relationship, such as urinary pH, creatinine, route of
administration, pattern of voiding and time elapsed after use of the drug.
2. WHO USES AMPHETAMINE/METHAMPHETAMINE?
Recent UNODC study conducted in India found that most of the respondents were

youths with the median age of 25 years. A quarter of the respondents (25%) were
females. About two third (63%) of the respondents had received college level education
and more than half were engaged in full time employment with about one fifth (19%)
reporting being in business. A similar proportion (19%) reported earning more than
Rs. 30,001/- per month. Majority (62%) were single.21
There is no definitive profile of a “typical” user. ATS are used for many reasons. For
example, sportspersons may use ATS to enhance their performance, long-distance truck
drivers may use it to keep awake on long journeys, labourers and porters engaged in
heavy physical activities may take ATS to make them feel stronger, and students may use
it to help them stay awake and study. Another group of ATS users comprises those who
take ATS for social reasons such as at parties, nightclubs or gatherings of friends and
acquaintances. Some are heavy and regular users who smoke or inject potent forms of
methamphetamine and also use a variety of other drugs. They are thus likely to
experience poor mental and physical health and may become dependent on
amphetamines. However, the majority of non-medical use is by young people who use
low-potency ATS, swallow or snort the drug, do not inject and are not dependent.
2.1 Who are more prone? Population groups at-risk of ATS use
l Children with ADHD
l Those suffering from PTSD
l Those suffering from mood disorders (self medication hypothesis)
l Those adolescent and adults already using inhalants, cigarettes, cannabis , alcohol
(gate way hypothesis)
l Men for sexual pleasure, indiscriminate sexual Behaviour
l Those with social phobia
l Those with conduct disorder or antisocial personality disorder
l Those who are impulsive and engage in high risk taking behaviour
l With personality traits of physical fearlessness and reward sensitivity
l Adolescent females with abnormal weight control behaviour
l Working/homeless children;
l Incarcerated and institutionalized youth;
l Sexually abused children
l Unemployed youth
l Sex workers and other workers in the entertainment/hospitality industry (e.g. clubs
and casinos)
l Young people frequenting places of entertainment such as clubs and discothèques

l Men who have sex with men (MSM), lesbian, bisexual and transgender youth, who
have higher rates of drug use including ATS than the rest of the community.22,23,24
3. AMPHETAMINE USE DISORDERS
Amphetamines produce feelings of euphoria and relief from fatigue, may improve
performance on some simple tasks, increase activity levels, and produce anorexia. The
dependence liability of the amphetamines is thought to be primarily related to their
euphorigenic effects.25 However, their dependence and misuse are viewed as resulting
from a process in which multiple interacting factors (social, psychological, cultural, and
biological) influence drug-using behaviour.26
Amphetamines have been used almost since their introduction. Taken intravenously,
the dependence potential of amphetamines is comparable to that of heroin or cocaine.27
The ease of synthesis frominexpensive and readily available chemicals makes possible
the wide spread of amphetamine dependence and abuse.
3.1 Dependence
Dependence on ATS is characterized by increasing tolerance to the drug, occurrence of
withdrawal symptoms, a preoccupation with the drug and an inability to reduce ATS use
despite signi? cant negative social, health or psychological consequences and
impairment.
l Tolerance can sometimes be observed when ATS users transit from non-injecting to
injecting as they begin to use higher doses of ATS per episode.
l Withdrawal from ATS is marked by fatigue, lethargy, sleep disturbances, appetite
disturbances, depression, irritability, psychomotor retardation or agitation and
strong craving.
The degree of methamphetamine dependence is strongly related to the route of
administration: injecting route of intake is associated with a high likelihood of
dependence.
3.2 Routes of amphetamine administration and patterns of amphetamine use
The patterns of amphetamine use may be classified as follows.28
l Instrumental use: amphetamines are exploited by the users to achieve desired goals,
such as improve concentration and ward off fatigue.
l Subcultural/recreational use: amphetamine stimulant properties are exploited to
allow the user to remain active for longer periods in social/recreational settings, such
as at music and dance events.
l Chronic use: for several reasons, such as craving, tolerance and withdrawal, some
amphetamine users turn to be chronic users to relieve unwanted effects of
abstinence.

Amphetamine may be ingested, snorted or smoked and, less commonly, injected. In

powder form, methamphetamine is generally swallowed or snorted. The crystalline
form of methamphetamine, which looks like glass and is often referred to as “ice”, is
typically smoked. When smoked or injected, ice reaches the brain rapidly and is
associated with a high risk of dependence. There is growing evidence that smoking
crystal methamphetamine has more harmful psychological effects and a higher
addictive potential than other forms of methamphetamine. Furthermore,
methamphetamine is sometimes mixed with other drugs and sold as “ecstasy” 3,4
(methylenedioxymethamphetamine – MDMA), a drug with hallucinogenic properties
that is frequently used in clubs and entertainment venues.
Within the dependence/harmful use continuum, there are several discernable patterns
of use. None are without potential risks though it is not clear whether occasional use
inevitably leads to regular or dependent use. These include a pattern of experimental
occasional use, usually with friends and in social settings. The pattern of intermittent
heavy binge use is more serious; it generally occurs on weekends and is precipitated by
party-going and the desire to stay awake. Such binge use may be occasional with large
gaps between binges. Some people use ATS regularly – daily or almost daily – and such
use may be accompanied by physical and psychological dependence. In addition,
polydrug useis very common among methamphetamine users. Alcohol, cannabis and
other psychostimulant drugs (such as ecstasy) are the most frequently used drugs.
3.3 Effects of ATS
Due to slight structural differences, methylamphetamine produces a stronger nervous
system response than amphetamine. Short-term effects of amphetamine and
methylamphetamine use may include sweating, headaches, insomnia, anxiety and
paranoia. High doses can result in blurred vision, hallucinations, tremors and stroke.
Long-term use may result in severe dental problems, reduced immunity, high blood
pressure, depression, impaired memory and concentration, deficits in motor skills,
aggressive or violent behaviour, anxiety, cardiovascular problems and kidney
failure.29-31
3.3.1 Acute Effects
Immediately after smoking the drug or injecting it- extremely pleasurable 'rush' or
'flash'.
l Enhanced mood and body movement
l Euphoria
l Increased respiration
l Insomnia
l Increased heart rate

l Increased blood pressure

l Reduced appetite
l Dilated pupils
l Perceptual abnormalities- visual and tactile hallucinations or illusions
3.3.2 Consequences of amphetamine use
A range of harms is associated with amphetamine use. Some are predominantly dose
related and others are a combination of dose and length of use.33
Table 2: Various Consequences of amphetamine use
Physical Physical Physical Physical Physical

consequences of consequences of consequences of consequences of consequences of
low-dose use high-dose use short-term use long-term use ATS use
Sweating Overdose Intoxication Drug dependence Precipitates
- Intoxication - Intoxication - Dehydration - Poor nutrition psychiatric
- Palpitation - High blood - Cardiovascular - Poor sleep problems
- Chest pain pressure problems (i.e. - Susceptibility to - Exacerbates
- Headache - Seizures rapid heart rate, illness including existing
- Hot and cold - Nausea irregular cardiovascular problems
flushes - Vomiting heartbeat and problems - Mood disorders:
- Reduced - Cerebral increased blood - Potential death confusion,
appetite haemorrhage pressure and from arrhythmias paranoia, anxiety,
- Increase in and death death from a or myocardial depression,
blood cardiac event) infarction suicidal ideation,
pressure - Overdose or stroke panic attacks,
- Euphoria - Hyperthermia obsession,
- Alertness and convulsions psychosis
- Reduction of - Decreased - Cognitive
fatigue appetite and impairment
- Talkativeness weight loss - Sleep disorders,
- Improved - Skin and teeth fatigue
physical problems - Agitation
performance - Sleep disorders - Increased
- Feelings of impulsivity
invincibility - Aggression and
while intoxicated violence
- Increased - Social and
high-risk family
behaviours disruption/
such as unsafe breakdown
sex - Unemployment

3.3.3 Health consequences of amphetamine use

A. Physical and neurological disorders due to amphetamines e. g.,
- Excitation syndrome: hyperthermia and tachycardia followed by circulatory
collapse with eventually fatal outcome,
- Vascular accidents: due to increased blood pressure, cerebral hemorrhage may
occur, but also myocardial infarction, both with an increased mortality risk,
- Cerebral convulsions and coma, followed by cardiovascular shock, an eventually
fatal outcome, and stereotype movements and choreic syndrome.
B. Amphetamine-induced mental disorders including
- Amphetamine Use Disorders (formerly Dependence and abuse as per DSM IV)
- Intoxication
- Withdrawal
- Intoxication delirium
- Psychotic disorders
- Mood disorders
- Anxiety disorders
- Sexual dysfunctions
- Sleep disorders
C. Health consequences of amphetamine use, e.g.,
- Human immunodeficiency virus infection
- Hepatitis
- Other sexually transmitted diseases
- Tuberculosis
- Other bacterial, fungal, and viral infections
D. Social consequences of amphetamine use
- Violence
- Crime
- Accidents
3.4 Hazards- Psychological
3.4.1 Paranoid psychosis (following long-term use)
l Resembles schizophrenia
l Persecutory delusion followed by auditory hallucinations, strange or unusual
beliefs, and thought reading.

l Vivid visual or tactile hallucinations

l Atypical paranoid psychosis – single dose exposure
l In vulnerable individuals, dose-independent ecstasy abuse can lead to
unpredictable and potentially dangerous neuropsychiatric sequelae.34
During the phase of chronic, high-dose consumption of amphetamines, many
amphetamine users may have the experience of paranoia and hallucination.35 This
conclusion has been supported by at least two experiments, which found that most
amphetamine users became psychotic within a week after a continuous administration
of amphetamines.36,37
The main characteristics of this psychosis are delusion of persecution, delusion of
reference, auditory hallucination, and visual hallucination.38 With further consumption,
the individual becomes increasingly exhausted, loses insight into his or her actions, and
may become violent and increasingly psychotic.39 Although amphetamine psychosis
may last longer than cocaine psychosis, it usually abate rapidly (within days) with the
cessation of amphetamine intake and the excretion of amphetamines.40 However, about
5-15% of the users who develop an amphetamine psychosis fail to recover completely.41
There is very little evidence about the risk factors of amphetamine psychosis. However,
the results of a recent study found that mental health problems, including hallucinations
and paranoia, significantly correlated with 4 factors.42 Those are: i) increasing severity of
dependence on amphetamines, ii) a larger number of mental health symptoms
experienced before starting to use amphetamines, iii) a larger average quantity of
amphetamine used in a day of use, and iv) a greater number of days on which
benzodiazepines had been used in the previous 6 months.
3.4.2 Depression - as part of withdrawal can occur
l Mixed affective state is more common in bipolar patients, poor outcome of episode
l Social withdrawal –in intoxicated state or due to psychosis
l Abnormal motor activity – stereotyped behaviour such as repeatedly assembling
and dissembling electronic equipment may occur in intoxicated or withdrawal state,
in delirium or in actively hallucinating persons
l Aggression
3.5 Amphetamine withdrawal
Amphetamine withdrawal has been less studied although it is a common problem with
a prevalent rate of 87% among amphetamine users.43,44 This prevalence is as high as
those of opiate withdrawal (91%) and cocaine withdrawal (86%). Although the duration
of amphetamine withdrawal tends to be much longer than cocaine withdrawal, the
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria for

amphetamine withdrawal are the same as those for cocaine withdrawal.32 The findings
of a factor analysis of amphetamine withdrawal symptoms suggest that this clinical
condition may be comprised of three factors.45 The hyperarousal factor comprises drug
craving, agitation, and vivid or unpleasant dreams. The reversed vegetative factor
comprises decreased energy, increased appetite, and craving for sleep. The anxiety
factor comprises loss of interest or pleasure, anxiety and slowing of movement.
Depressive mood is a prevalent symptom and should be considered as a symptom
incorporated in more than one factor or more. Although the symptoms occurring during
amphetamine withdrawal may be over in four or five days, some of the symptoms may
continue for weeks or months.41, 46
Table 3: Phases of ATS withdrawal
Phases Time duration Common sign and symptoms

Crash Start at 12-14 hours after Fatigue, agitation, irritability, Depression,
last amphetamine use and muscle ache, Sleep disturbance
subsides by 2-4 days
Withdrawal Between 2-4 days to 2-4 Strong craving ,Fluctuating between irritability,
weeks, peak in severity anxiety, restlessness and agitation, low energy
over 7-10 days
Extinction Weeks to months Gradual resumption of normal mood with

episodic fluctuation in mood and energy levels
alternating between irritability, restlessness,
anxiety, agitation , fatigue, lack of energy
-episodic craving and disturbed sleep
3.6. Use during pregnancy and perinatal period

l Related with more pregnancy complications
l Anaesthesia related complications
l Small for gestational age children
l Infants are also psychosocially disadvantaged and are at greater risk for abuse and
neglect47, 48
3.7. Death among ATS users
l Most common complication – Hyperthermia
l Rhabdomyolysis with acute renal failure
l Overdose, toxicity49,50

3.8. Consequences of amphetamine use in the context of polydrug use

l Methamphetamine toxicity is increased when taken in combination with
alcohol, cocaine or opiates.
l Use of alcohol and methamphetamine in tandem can be dangerous – it increases the
blood pressure, placing a greater burden on the heart. Methamphetamine can also
disguise the effects of alcohol, which may increase the risk of alcohol poisoning and
accidents due to a false sense of feeling sober and in control.
l Use of cannabis and methamphetamine in tandem has been shown to increase
psychotic symptoms in some users.
l Heroin and methamphetamine used together can cause respiratory depression
which may induce cardiac failure. Methamphetamine can also increase the risk of
heroin overdose.
l The combination of methamphetamine and cocaine has been shown to substantially
increase the cardiotoxic effects of both drugs.
4. MANAGEMENT
4.1 AMPHETAMINE PSYCHOSIS
It has been estimated that the prevalence of psychosis is 11 times higher among regular
ATS users than among the general population, and that 23% of regular ATS users will
experience symptoms of psychosis within a given year. The treatment of ATS-induced
psychosis is short-term antipsychotic medication; symptoms usually abate rapidly
within days of stopping ATS intake.
It has long been believed that dopamine antagonists, such as chlorpromazine,
haloperidol, and thioridazine, are effective for the treatment of this psychosis [III].51, 52 In
addition, the use of ascorbic acid can accelerate the renal elimination of
amphetamines.[III]53
4.2 Treatment of ATS withdrawal
ATS withdrawal is generally not medically hazardous and fatalities directly attributable
to ATS withdrawal are rare. The severity of withdrawal is dependent upon the dose and
frequency of use, type of stimulant used, mode of administration, other drug use,
current health problems and the duration of use. Supervision by health-care staff is
indicated only in severe cases. During and after withdrawal, users must be regularly
monitored for their physical and mental state as withdrawal can lead to severe
depression. Different symptoms become evident at different stages of the withdrawal.
However, no medication has been demonstrated to be effective in alleviating
amphetamine withdrawal, but some medications may be useful with some symptoms.
Antidepressants have been used for withdrawal-induced depression with some benefit,

although onset of action is delayed and relapse to use while taking antidepressants can
result in hypertension or serotonin syndrome. Mirtazapine is used at Drug and Alcohol
Services South Australia and has resulted in some improvement in symptoms. It may be
continued for depressive symptoms if response to treatment is evident. Short-term use of
benzodiazepines (diazepam 5 to 10mg QID SOS) and antipsychotics (olanzapine 2.5-
5mg BD SOS) for control of irritability and agitation can be helpful, particularly in the
inpatient setting. Care should be taken to limit access to large quantities of medications
and to avoid development of benzodiazepine dependence. These medications should
be prescribed for a maximum of seven to 10 days. Modafinil is also used at Drug and
Alcohol Services South Australia and has been demonstrated to result in some
improvement in symptoms, but this is not an approved medication for amphetamine
withdrawal treatment. The mainstay of treatment is supportive care and counselling.54
4.3 Treatment of amphetamine use disorders
4.3.1 Pharmacological treatment
Pharmacotherapies for amphetamine or methamphetamine dependence are based on
different underlying mechanisms that may:
a. alter the neurobiology of reinforcement or reward from the drug,
b. attenuate the negative reinforcing effects of withdrawal from and craving for the
drug, or
c. ameliorate comorbid psychiatric vulnerabilities that co-occur and that can interfere
with recovery
The medications evaluated in trials for pharmacotherapies for amphetamine or
methamphetamine dependence have mechanisms of action that can be categorized as
antagonists or agonists. Antagonist therapy approaches use medications that block the
action of the agonist to attenuate or eliminate the positive reinforcing effects of acute
methamphetamine intoxication. Antagonists compete with endogenous monoamines
but have no intrinsic activity at the receptor site. In contrast, agonist therapies are
medications that bind to and trigger responses from receptors involved in the addiction
process, often mimicking the action of monoamines involved in the reinforcement,
withdrawal symptoms and motivational aspects of methamphetamine or amphetamine
use.55
4.3.1.1 Antagonist strategies
4.3.1.1.1 Naltrexone: It is an opioid receptor antagonist. Since, the primary positive
reinforcing effects of ATS are mediated by dopamine, and opioid receptors partially
modulate dopaminergic effects these receptors may act as a relevant pharmacological
target. The results of an open-label trial of naltrexone for amphetamine dependence
were encouraging.56 A Swedish randomized trial included 80 treatment-seeking

amphetamine-dependent adults who were grouped to placebo or 50 mg of naltrexone.57

In an intention-to-treat analysis, naltrexone outperformed placebo in terms of both
mean numbers of negative urine samples and continuous abstinence rates. However,
the limitation of study was that the retention and adherence was suboptimal. It is
important to note the exclusion criteria: the trial required a two-week period of
abstinence prior to randomisation, which might have excluded severely dependent
patients.55
Tiihonen et al, (2012) assessed the naltrexone implant in a 10-week trial in randomized
manner for individuals with comorbid opioid and amphetamine dependence. The
results were encouraging for naltrexone in term of retention and proportion of drug-free
urine samples.58
4.3.1.1.2 Serotonin Dopamine antagonist: Two small open-label trials evaluated
risperidone in methamphetamine-dependent adults to show acceptability and
decreases in weekly methamphetamine use that correlated with plasma risperidone
levels.59,60 A randomised trial of quetiapine and risperidone in 80 adults hospitalised
with bipolar disorder and co-occurring cocaine or methamphetamine dependence
reported that both equally reduced bipolar symptoms and drug cravings, with
reductions in cravings associating with reductions in stimulant use . However, in
experimental condition, neither haloperidol nor risperidone attenuated the
euphorigenic effects of methamphetamine in healthy volunteers, dampening rationale
for further evaluation of dopamine antagonists.61,62
4.3.1.1.3 Dopamine partial agonist: Studies on partial agonist aripiprazole have not
observed any difference in methamphetamine use.55
4.3.1.2 Agonist strategies (Oral substitution approaches)
There are as yet no approved pharmacologicaltreatments for ATS users which are based
upon the philosophy and principles of substitution treatment (such as methadone or
buprenorphine for opioid dependence). Potential oral substitution/
pharmacotherapeutic interventions are still in the experimental stage but could be
useful when they become available for chronic and dependent ATS users who are
unable to cease use or even ameliorate their high-risk behaviours.
The efficacy of substitution therapy for ATS users is not known, even though the practice
appears to have gained a degree of clinical acceptance at least in the United Kingdom.
The literature is not extensive and controlled trials are few. There is a strong and growing
case for rigorous evaluation of substitution therapies combined with tailored
psychosocial interventions to achieve improved outcomes for amphetamine users.
(IV).63 A randomized study included 41 long-term dependent amphetamine user
seeking treatment. Half of treatment seekers were given amphetamine and another half
were kept on counseling only. There was reduction in use of street amphetamine,
however treatment subjects appeared attended counseling session regularly. (Ib)64
4.3.1.2.1 Dexamphetamine: Agonist therapies produce behavioural and

neurobiological effects that are comparable or identical to the drug of addiction.65
Dexamphetamine increases extracellular levels of dopamine through a carrier-
mediated exchange at presynaptic vesicles.A 12 weeks randomized trial assigned
methamphetamine-dependent participants to receive up to 110 mg/day sustained-
release dexamphetamine (N = 23) or placebo (N = 26) for 12 weeks. Those in the
dexamphetamine condition completed an average of 86 days compared with the
placebo condition (49 days) but no effect on methamphetamine use was observed.
Although some decrease in craving for methamphetamine was observed with
dexamphetamine treatment, no improvement in drug use or retention were observed in
a subsequent trial.66
4.3.1.2.2 Methylphenidate: Additional support for an agonist approach is available
from the study by Tiihonen (2007).58 In this 20-week, randomised, double-blind,
placebo-controlled trial of aripiprazole, methylphenidate or placebo among
participants dependent upon injection use of amphetamine, participants assigned to the
54 mg/day slow-release methylphenidate condition (N = 17) had significantly fewer
amphetamine-positive urine samples than placebo-treated patients (N = 19; odds
ratio=3.77; 95% confidence interval 1.55, 9.18).
4.3.1.2.3 Modafinil: Studies on modafinil - both open-label and randomized -
conducted in HIV –positive patients and methamphetamine dependent adults found
few adverse effects and no indications that medication was habit-forming or a diversion
risk. However modafinil was no more effective than placebo in retention of treatment.67
Anderson et al, (2012) completed a trial of 210 methamphetamine dependent
individuals randomised to placebo, or 200 mg, or 400 mg of modafinil. There was no
evidence of benefit for either medication condition in terms of percentage of
participants with a week of abstinence or retention. The authors caution, however, that
due to poor medication compliance, the trial does not represent a definitive test of the
efficacy of modafinil.68
4.3.1.2.4 Bupropion: Although not strictly considered an agonist, bupropion functions
as a mild stimulant and antidepressant. Bupropion is a nonselective inhibitor of the
dopamine and norepinephrine transporters and also acts as an antagonist at nicotinic
acetylcholine receptors. Bupropion increases dopamine transmission in both the
nucleus accumbens and the prefrontal cortex through inhibition of the dopamine
transporter. Various randomized placebo-controlled double-blind trials with sample
sizes between 30-150 in different type of population are available.69-71 On primary
outcomes of retention and Methamphetamine-free urine samples, Methamphetamine
use and cravings, bupropion sustained release did not outperform placebo. However,
recruitment and retention were 'feasible' and bupropion was well tolerated, as
indicated by the absence of adverse events and acceptable medication
adherence.55, 68,72,73,

4.3.1.3 Other treatment strategies

4.3.1.3.1 Serotonergic medications: A study assessed the selective serotonin reuptake
inhibitor sertraline (50 mg twice daily) in a four-arm randomised design. Two hundred
and twenty-nine participants were assigned to sertraline only, sertraline and
contingency management, placebo and contingency management, or placebo only.
Contingency management significantly improved methamphetamine use outcomes,
while participants assigned to the sertraline-only condition resulted in poorer retention
and lower likelihood of sustained abstinence than the other treatment conditions.5
The evidence-base for the treatment of amphetamine use disorders is rather limited. The
small number of treatment studies may reflect the fact that this issuehas been received
less attention than the treatment for other substances, e.g., alcohol, heroin, or cocaine.
The evidence shows that fluoxetine, amlodipine, imipramine and desipramine have
been tried but demonstrate very limited benefits foramphetamine dependence and
abuse. Fluoxetine may decrease craving in short-term treatment. Imipramine
mayincrease duration of adherence to treatment in medium-term treatment. Apart from
these distal benefits, no otherbenefits, in particular the proximal ones can be found. This
limited evidence suggests that no treatment has been conclusively demonstrated to be
effective for the treatment of amphetamine dependence and abuse.
A review by (WHO, 2001) (I)74 for treatment of amphetamine dependence and abuse
included the results of four studies (Batki et al, 2000; Batki et al, 2001; Galloway et al,
1996; Tennant et al, 1986). While two studies compared fluoxetine 40 mg/day (Batki et
al, 2000), amlodipine 10 and 5 mg/day (Batki et al, 2001) and desipramine 100-150
mg/day (Tennant et al, 1986) with placebo, the other compared imipramine 150 mg/day
with imipramine 10 mg/day (Galloway et al, 1996). Three included studies (Batki et al,
2000; Batki et al, 2001; Tennant et al, 1986), therefore, should be considered as
placebo, randomised, double-blind controlled studies. The other study should be
considered as a randomised, doubleblind controlled study of imipramine 150 mg/day
and imipramine 10 mg/day although the investigators considered that imipramine 10
mg/day was a placebo.
Short-term, proximal outcomes presented in three studies were: i) number or
percentage of amphetamine positive urines (Batki et al, 2000; Galloway et al, 1996); ii)
number or percentage of amphetamine-use days (Batki et al, 2000; Galloway et al,
1996); iii) frequency of amphetamine use (Batki et al, 2000) and iv) amount of
amphetamine consumed (Batki et al, 2001).
Short-term, distal outcomes presented in four studies were: i) craving (Batki et al, 2000;
Batki et al, 2001; Galloway et al, 1996); ii) severity of dependence, abuse or addiction as
measured by Addiction Severity Index (ASI) (Batki et al, 2001); iii) discontinuation rate

(Batki et al, 2000) and iv) days of adherence to treatment (Batki et al, 2000; Batki et al,
2001; Tennant 1986).
4.3.1.3.2 5-HT3 antagonist (Ondansetron): Johnson and colleagues assessed three
doses of ondansetron in a double-blind placebo-controlled trial with 150
methamphetamine-dependent participants. Significant differences were not observed
for the medication at any of the doses in reducing methamphetamine use or any reports
of withdrawal, craving or severity of dependence.75
4.3.1.3.3 Mirtazapine: Colfax reported outcomes of a trial of mirtazapine (15 mg twice
daily) in 60 men who have sex with men showing men assigned to receive mirtazapine
showed fewer methamphetamine-positive urine samples compared to those assigned to
placebo.76
4.3.1.3.4 GABAergic agents: The GABA system activation exerts an inhibitory effect on
the reward system of dopaminergic tract. This feature suggests that GABA agents may
have some efficacy in attenuating the reinforcing effects of stimulants. Some preclinical
evidence suggested modest efficacy for cocaine dependence of the selective GABAB
agonist baclofen, and a clinical trial found some support as a treatment for cocaine
dependence.77
In a randomised, placebo controlled trial of a proprietary concoction of flumazenil
injections (a benzodiazepine antagonist), gabapentin and hydroxyzine in 120
methamphetamine-dependent adults78, no effects were seen on methamphetamine use,
treatment retention or drug craving. Elkashef et al. (2012)79 assessed topiramate with a
target dose of 200 mg/day in 140 methamphetamine dependent adults. There was no
clear evidence of efficacy for the medication; however, among individuals who were
abstinent at the beginning of treatment, topiramate appeared to facilitate abstinence
during the second half of the trial.
4.3.1.3.5 N-acetyl cysteine: Recently, a double blind randomized cross over study
conducted to evaluate efficacy of N-acetyl cysteine in treatment of methamphetamine
dependence found that this drug is effective in suppressing methamphetamine
craving.80
4.4 Psychosocial treatment approaches
Only few controlled trials of a psychosocial intervention for amphetamine dependence
and abuse have been found.81 However, recently web based intervention has been used
for treatment of users of amphetamine type stimulant.82 To meet the challenge of ATS
treatment, an eclectic “stepped-care approach” has been developed which aims to
provide individualized, evidence-based and voluntary treatment. The “stepped-care”
approach uses psychosocial interventions at various stages of drug use. It aims to
increase access to treatment, provide support to help users reduce or cease use, and

mitigate the social, health and legal problems associated with continued use.
The services provided under the heading of “stepped care” include community-based
prevention and health promotion, creating awareness that there are help/treatment
options for ATS users, self-help groups, brief interventions of motivational interviewing
and cognitive–behavioural therapy (e.g. one to four sessions), intensive individual
counselling, detoxification and withdrawal services, crisis interventions and emergency
care, as well as long term rehabilitation and reintegration services. Research suggests
that cognitive–behavioural therapy applied in a stepped-care approach is the treatment
of best practice for ATS use.
There are many activities, which need to be undertaken at every step. Thus, case
management and counselling are important at every stage – though different techniques
and different intensities are indicated for ATS users, depending on their profiles. Also
important is the provision of opportunities for ATS users to undergo vocational training
and assistance to gain employment, as well as in improving family relations, dealing
with legal problems and assisting in the development of new recreational activities and
social networks in the community.
4.4.1 Interventions in the community and in primary health-care settings (Steps one
and two)54
Providing services for ATS users in the community is the first step. Many ATS users are
occasional users who require information and education about the risks of ATS use, as
all ATS users may at some time require emergency care and management of acute
withdrawal. All ATS users should be provided with condoms since ATS use tends to
increase libido and hence the risk of unsafe sex. Needles and syringes should be
provided to all ATS injectors.
Providing services for ATS users in the community and in primary health-care settings
has many benefits including help in dispelling the stigma and discrimination as ATS
users are not singled out.
ATS users are exposed to a range of evidence- and community-based psychosocial
interventions as appropriate, without necessarily providing a specific therapeutic
approach. It is a setting where knowledge of community resources is available so that
referral can easily be made to specialized drug treatment facilities or other ancillary
services. It is the setting to which drug users are likely to return if referred to specialist
care. It is in the community that resources for rehabilitation and reintegration are
mobilized. It is the most cost-effective option for ATS users due to the lower costs of
transportation to such health facilities as well as for the health sector in the delivery of
services to ATS users and associated costs of referral to other standard health services
such as HIV/ AIDS and tuberculosis.

Table 4 : Stepped care approach54
Steps for ATS Users Types of ATS User Types of activities

One Occasional ATS users Personal care activities: Self/family
believed to be at Care,Self-help groups, informal
relatively low risk communitybased care
NGO activities: Information about the risks
of drug use, brief counselling, peer outreach
and education, drop-in centres, skills and
vocational training, rehabilitation and
reintegration services
Two “Problem” ATS users Drug services in primary health-care settings:

assessment, brief counselling, harm
reduction information, needle and syringe
programmes, referral to specialist services if
required, assistance with basic symptomatic
detoxification and withdrawal. Referral
back to the community for support,
rehabilitation and reintegration services
and/or to expert care
Three Heavy/dependent ATS Specialized, voluntary drug dependence

users clinical care: Assessment of dependence,
pharmacologically assisted withdrawal, harm
reduction, needle and syringe programmes,
outpatient and/or inpatient or residential
treatment and specialized counselling,
referral to rehabilitation and reintegration
services, and back to the community for
support
4.4.2 Psychosocial treatment

The key features of successful psychosocial treatment interventions for drug problems
are as follows:
a. Seek the input of drug users to determine what works
b. Do not blindly apply what seems to work for other drug treatment. Interventions
must be appropriate. Adopt evidence-based approaches.
c. Adopt a holistic approach that addresses the broader socioeconomic issues rather
than only the drug use.
4.4.3 Various types of Psychosocial treatment54
l Cognitive–behavioural therapy (CBT)

l Motivational interviewing (MI)

l Contingency management (CM)
l Harm reduction and risk reduction
l Brief interventions (BI)
l Matrix model
l Twelve-step programme
Table 5 : Psychosocial intervention54
Intervention Types of activities

Cognitive-behavioural Based
l on Social Learning Theory9
therapy (CBT) Key concepts include: encouraging and reinforcing
l
behaviour change
Recognizing and learning to avoid high-risk settings
l
Improving coping skills

l
Managing and avoiding trigger situations associated with

l
drug-use behaviours
Learning to deal with drug craving.
l
Motivational Assumptions
l are that people change their thinking and
interviewing (MI) behaviour according to a series of identifiable stages
It is possible to influence the natural change process with
l
“motivational” interviewing techniques.
Key concepts include establishing a “therapeutic alliance”
l
showing empathy, providing feedback, helping the client to
reframe his/her behaviour and thus reinforcing change.10
Contingency Contingency
l management is the systematic application of
management (CM) reinforcement/conditioning principles.
Basic assumptions include the belief that drug use behaviour
l
can be controlled using reinforcement procedures.
Positive reinforcement takes the form of verbal praise,
l
earning programme privileges or rewards.
Typically, the individual can earn larger-value rewards for
l
longer periods of continuous abstinence from drugs.
Harm reduction and Designed

l to help drug users minimize the adverse
risk reduction consequences of their drug use.
The interventions that make up the package of harm/risk
l
reduction include provision of information, education and
counselling, peer outreach, distribution of condoms and

clean needles and syringes, ensuring easy access to primary

health care, e.g. services for HIV/voluntary counselling and
testing (VCT) and antiretroviral medication, drug counselling
and treatment, crisis management etc.
Matrix model Developed

l in the 1980s by the Matrix Institute on
Addictions group in Southern California, USA
It is a comprehensive behavioural treatment approach that
l
combines behavioural therapy and family education
including cognitive–behavioural therapies (see above),
relapse prevention techniques, positive reinforcement for the
abstinence-using components of motivational interviewing,
contingency management, provision of accurate
psychoeducational information, and introduction to the
12-step recovery programme (see below).
It employs regular urine testing.
l
The programme thus focuses on encouraging behaviour

l
change and not on dealing with the underlying causes of
drug use or psychopathology.13,14,15
Twelve-step programme The “12-step

l programme” is a self-help programme based on
a fellowship of ex-drug and/or alcohol users and plays a key
role in relapse prevention by offering mutual support.
5. CONCLUSION
ATS is a rather new category of substance for most Indian professionals. At present the
clinical experience is limited. Even globally, there is scanty evidence-base about
effectiveness of various treatment approaches. Clearly, more research is needed in this
area to expand the evidence-base globally, as well as in our country.
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DISORDERS ASSOCIATED WITH USE OF
“CLUB DRUGS”
Kaustav Chakraborty
Rajarshi Neogi
On behalf of
2016
Club Drugs
CONTENTS
Executive Summary
1. Introductory section
1.1 Introduction
1.2 Scope and methodology of developing the guideline
1.3 Data Search Methodology
2. Club drugs
2.1 Epidemiology of club drugs
2.2 MDMA
2.2.1. Clinical pharmacology
2.2.2. Neurobiology
2.2.3. Clinical and adverse effects
2.2.4. Management
2.2.4.1. Management of acuteMDMA toxicity
2.2.4.2. Management of harmful use and dependence of MDMA
2.3 Ketamine
2.3.2. Neurobiology
2.3.4. Management
2.3.4.1. Management of acute toxicity of Ketamine
2.3.4.2. Management of Ketamine dependence and withdrawal
2.4 Gamma-hydroxybutyrate (GHB)
2.4.2. Neurobiology
2.4.4. Management
2.4.4.1. Management of acute GHB toxicity
2.4.4.2. Management of GHB withdrawal
2.4.4.3. Management of GHB dependence

2.5. Flunitrazepam
2.5.2. Neurobiology
2.5.4 Management
2.5.4.1. Toxicology and detection
2.5.4.2. Management of Flunitrazepamintoxication/dependence
2.6. Lysergic acid diethylamide (LSD) and related hallucinogens
2.6.2. Neurobiology
2.6.4. Management
2.6.4.1. Management of hallucinogen toxicity
2.6.4.2. Management of hallucinogen dependence
2.6.4.3. Management of HPPD
3. General principles in the management of club drugs intoxication / harmful use/
dependence
4. Club drugs: Indian scenario
5. Conclusion

Club Drugs
EXECUTIVE SUMMARY
Club drugs are a group of newer synthetic addictive substances which are increasingly
used in 'clubs' or 'raves' along with loud, electronic 'techno rock' music and all night
dancing by the sensation seeking youths and/ or adults. There is very little data regarding
the prevalence of club drugs harmful use/ dependence particularly from India. The data
is only in the form of case reports or case series, news paper reports, crime bureau or
narcotics department data. But it can definitely be said that their use is on the rise and
clinicians will be challenged by the various health problems that are known to arise
from the use of these substances. In our discussion we will use the term 'club drugs' in
reference to MDMA, Ketamine, GHB, Flunitrazepam, and LSD/related substances. We
have developed a clinical practice guideline based on existing evidence, with emphasis
on available Indian data, to assist practitioner and patient decisions about appropriate
health care for specific clinical circumstances, e.g., acute intoxication, harmful use,
dependence and withdrawal state due to use of club drugs.
MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE or ECSTASY)
Management of acute MDMA toxicity
Laboratory identification of MDMA is difficult. As many as one-third of immunoassay
urine screens have failed to detect it in standardized specimens. In acute MDMA
toxicity short period of hospital stay is recommended (C). Severely dehydrated patients
may require intravenous fluid (C). Patients with severe hyponatremia may require fluid
restriction (C). Gastric decontamination with active charcoal is indicated if presentation
is within 1 hour of ingestion (D). Hyperthermia can be treated with Dantrolene (C) or
benzodiazepine sedation (D).
Management of harmful use and dependence of MDMA
Psychosocial treatment is the mainstay for chronic harmful use of MDMA (D, S). No
speci? c guidelines for psychosocial intervention have been described and validated for
chronic ecstasy users. For those that do seek help, typical treatment approaches include
individual and group counselling, cognitive behavioural therapy, and relapse
prevention technique.
KETAMINE
Management of acute toxicity of Ketamine
The diagnosis of ketamine should be considered when people (especially young
people) present with agitation, tachycardia and either visual hallucinations or
nystagmus. No antidote exists for ketamine overdose. Supportive care with special
attention to cardiac and respiratory function is the mainstay of treatment as the effects of
the drug are usually short lived (S). Patient should be kept in a quiet environment with

minimum external stimulus (S). Activated charcoal can be used in the presence of co-
ingestant or if the patient presents very early (D). Benzodiazepines cane be used for
agitated or hyperthermic patients (D).
Management of Ketamine dependence and withdrawal
Psychosocial treatments are mainstay of ketamine dependence (D). Ketamine
withdrawal is characterized by anxiety, shaking, sweating, palpitations and carving for
the drug. This can be treated with tapering dose of diazepam modified from alcohol
detoxification regimen (D).
GAMMA-HYDROXYBUTYRATE (GHB)
Management of acute GHB toxicity
It may be difficult to differentiate GHB poisoning from other sedative hypnotic
intoxications. GHB is detected by routine urine screens in the western countries which
are not available in India now. A sensitive and specific GC-MS method using selective
ion monitoring has been developed for the quantification of GHB in blood. Supportive
care is the mainstay of treatment. Endotracheal intubation may be required if vomiting is
present (D,S). Decontamination with activated charcoal should be considered in
patients who are alert, stable and have a protected airways (D). Atropine can be used for
hemodynamically unstable patients (D). Myoclonic movements and seizures may be
treated with lorazepam or diazepam (D). There are no specific antidotes for GHB
poisoning
Management of GHB withdrawal
The GHB-related withdrawal syndrome seems consistent with other hypnotic/sedative
withdrawal syndromes. Benzodiazepines are the first line of treatment for GHB
withdrawal (D). Baclofen and barbiturates can be used as second-line adjuncts (D).
Valproic acid, carbamazepine, gabapentin, chloral hydrate, baclofen, clonidine,
paroxetine, beta blockers, bromocriptine, trazadone, fentanyl, propofol, and
antipyschotics have been tried sporadically (D).
Management of GHB dependence
Psychosocial interventions are the mainstay of treatment of GHB dependence (D).
Motivatonal counselling, contingency management, CBT based relase prevention
techniques, group therapy, occupational therapies can be tried.
FLUNIRAZEPAM
Management of flunitrazepamintoxication / dependence
Management of Flunitrazepamoverdose/dependence is similar to other
benzodiazepine overdose/dependence which has been elaborately dealt in the

Club Drugs
previous volume of IPS-CPG which provided the guidelines for the management of
sedative-hypnotic use disorders. Decontamination with activated charcoal is done for
patients with secured airways and who present early (D,S). Flumazenil can be used to
reverse the effects of Flunitrazepamtoxicity (D). Flunitrazepamdependence is managed
by titrating doses of long acting benzodiazepines similar to other benzodiazepine
dependence (D).
LSD AND OTHER RELATED HALLUCINOGENS
Management of hallucinogen toxicity
The management of acute toxicity resulting from the use of hallucinogens will in part
depend on the hallucinogenic substance consumed.Attempts to 'talk the patient down'
first must be instituted. Sympathetic, non-judgemental reassurance, support and
observation are often sufficient.Patient should be placed in a quiet, well lit room with
minimal external stimuli (S). Benzodiazepines, diazepam or lorazepam are the
mainstay of treatment, particularly in presence of agitation (D). Antipsychotics can be
considered as second line treatment (D).
Management of hallucinogen dependence
The use of LSD or other classic hallucinogens does not appear to lead to dependence.
Typically there is no persistent and compulsive pattern of use and the use of
hallucinogens is not associated with any recognized withdrawal syndrome.
Management of HPPD (Hallucinogen persisting perception disorder)
Hallucinogen persisting perception disorder (HPPD) and 'flashbacks' have been
associated with use of classic hallucinogens in particular, although these concepts
remain uncertain. HPPD can persist for months or years after the use of
hallucinogens.Several classes of antidepressants, anxiolytics, antipsychotics, COMT
inhibitor, naltrexone, levodopa, clonidine, lamotrigine and citalopram can be used to
treat HPPD (B). Lamotrigine may be a promising agent in the treatment of HPPD (D).
GENERAL PRINCIPLES IN THE MANAGEMENT OF CLUB DRUGS INTOXICATION /
HARMFUL USE / DEPENDENCE
No standard treatment protocol has been identified for club drug overdose. Basic
management should include cardiac monitoring, pulse oximetry, urinalysis, and
performance of a comprehensive chemistry panel to check for electrolyte imbalance,
renal toxicity, and possible underlying disorders. Harm reduction strategies have been
proposed which emphasizes that buildings meet safety and health standards, adequate
security is provided to accommodate the large number of attendees and “ravers” are
educated about health effects by trained volunteers.Suspicion of a club drug overdose
or toxicity is essential. Except for GHB, club drugs cannot be detected through routine
toxicological screens. Airway, breathing and circulation should be maintained (S).

Gastrointestinal decontamination with activated charcoal is recommended if ingestion

has happened within last 1 hour (S). Hyperthermia and Serotonin syndrome should be
managed with tepid sponging and cyproheptadine/chlorpromazine respectively (S).
Flumazenil may be administered to reverse the effects of flunitrazepamtoxicity (D, S).
Psychosocial interventionsin various forms e.g. motivational interviewing, contingency
management, CBT based relapse prevention, community reinforcement approach,
behavioural therapies, socialbehaviour network therapy, supportive expressive
psychotherapy can be effective for the management of club drugs dependence (D).
Long term community intervention programs e.g. 'Club against Drugs' has shown some
promise (C).

Club Drugs
1. INTRODUCTORY SECTION
1.1 INTRODUCTION
'Raves' are parties with loud, electronic “techno-rock” music, laser light shows, and all-
night dancing held in clandestine locations, including warehouses, nightclubs, and
farm fields.1 They first became popular in Great Britain in the late 1980s.The
underground or noncommercial music featured at raves which is produced by
computers and include little or no vocals is distinct from the music played at
conventional nightclubs. Following bans in some countries the rave parties moved in to
legitimate nightclubs. A “raver” is a person who has an exciting and uninhibited social
life and regularly goes to raves. Not all ravers use drugs; however, many illicit drugs are
available at raves and are used liberally to enhance the “vibe”.2 Here, it would be
worthwhile to clarify that words like 'rave drugs', 'club drugs' and 'party drugs' have
been used interchangeably in the literature. The U.S. National Institute on Drug Abuse
(NIDA) in its “Community Alert on Club Drugs,” defined “club drugs” as MDMA (3,4-
methylenedioxymethamphetamine, or Ecstasy), Ketamine, Gamma-hydroxybutyrate
(GHB), Flunitrazepam, Methamphetamine, and Lysergic Acid Diethylamide (LSD).3 On
the other hand, the U.S. Office of National Drug Control Policy identifies four specific
club drugs: MDMA, Ketamine, GHB, and Flunitrazepam.4 Methamphetamine and LSD
have been inconsistently included in the category of the club drugs. In addition, these
two drugs have a longer history of misuse in comparison to the other four which came to
the scene much later (MDMA being first reported in 1985).
In our discussion we will use the term 'club drugs' in reference to MDMA, Ketamine,
GHB, Flunirazepam, and LSD/related substances to avoid further confusion.
Methamphetamine has been deliberately left out because it will dealt in a separate
chapter on amphetamine like stimulants. These drugs are being used in an expanding
variety of venues by groups who differ in terms of age, gender, sexual orientation, and
race/ethnicity5. Each of these drugs has very different pharmacologic properties,
physiological and psychological effects, and potential consequences (Table 1).

130
Table 1: Pharmacological and clinical profile of club drugs
MDMA Ketamine GHB Flunitrazepam LSD/related

hallucinogens
Manner of use Tablet/Capsule; Liquid – injected, Liquid; often mixed Tablet; typically Tablet; typically
ingested orally, can be added to items to be with alcohol – effects ingested orally; ingested orally;
crushed/snorted/ smoked. Powder – amplified6 crushed and snorted sublingually/ buccally
dissolved/injected6 dissolved in drinks,
smoked, snorted or
dissolved and injected16
Onset of action; 30 to 60 minutes; 5.8 Variable; elimination 15-30 minutes after an 15-20 minutes; 18 - 26 LSD ~ 60 mins
T1/2 ± 2.2 hours t1/2is ~2 hours oral dose; 22-28 hours
minutes
Therapeutic use Not strongly supported Veterinary anaesthetic, To treat cataplexy To treat insomnia Earlier to treat alcohol
also used as associated with narco- dependence; now not
anaesthetic in India for lepsy licensed for clinical use
Humans
Clinical effects Feelings of empathy, Low dose: relaxation 10 mg/kg: euphoria, 1- or 2-mg dose: Euphoria, mild
energy, psychomotor (K-land); Higher dose: amnesia, and reduces anxiety, stimulation, enhanced
drive, self-confidence, dream-like state, hypotonia; 20–30 inhibition, and appreciation of
depression, hallucinations, visual mg/kg: somnolence; > muscular tension; musicand lights,
derealization, distortions, sensation 50 mg/kg: Higher doses: visually appealing
depersonalization, well- of near-death unconsciousness and anterograde amnesia, distortions,
being, positive mood, experiences (K-land)16- coma; anxiety lack of muscular intensi? cation of
18
heightened perception & , nystagmus, reduction, increases control, and loss of sensual or sexual
sensory awareness, increased tone, relaxation, enhances consciousness.23 feelings,altered sense
increase in the purposeful movements, libido, agitation, of time and place, and
sensuality of sexual amnesia, nystagmus, ataxia, a sense of shared and
experiences, inhibition heightened signi? cance
of orgasm and erectile of the situation24
dysfunction, mydriasis7-11
© Indian Psychiatric Society 2016

MDMA Ketamine GHB Flunitrazepam LSD/related
hallucinogens
Club Drugs
Toxic effects Irritability, fatigue, Increased heart rate, Sleep induction, Decreased body 'Bad trip', characterised
nausea, loss of hypertension, cognitive tremors, agitation, temperature and blood by anxiety, fear/panic,
appetite, weight loss, and psychomotor seizures, GI symptoms, pressure, sedation, dysphoria and/or
tachycardia, impairment, nausea, CNS & respiratory cognitive & paranoia. Distressing
hypertension, tremors, respiratory depression, depression, dizziness, psychomotor effects can be sensory
tics, jaw clenching, immobility, anxiety, confusion, impairment, visual (e.g. frightening
serotonin-syndrome, dissociation, hallucinations, apnea, disturbances, dizziness, perceptions), somatic
anxiety, bruxism, depression, recurrent bradycardia, confusion, GI (e.g. distressing
thought flashbacks, delirium, unconsciousness, disturbances, urinary awareness of
© Indian Psychiatric Society 2016

disorder/psychosis, amnesia, schizophrenic sudden reversible retention. physiological
difficulty concentrating, symptoms, loss of coma with abrupt processes),
hyperthermia, consciousness, awakening and personal(e.g. troubling
hyponatremia, respiratory depression, violence, death16,22 thoughts or feelings) or
hypertension, catatonia, death1,16,17,19,20 even metaphysical (e.g.
dysrhythmias, liver feelings about evil
toxicity, ataxia, force; tachycardia,
neurotoxicity, tachypnoea, agitation,
rhabdomyolysis, hyperpyrexia and
disseminated hypertension
intravascular
coagulation (DIC),
seizures, death12-15.
Dependence No dependence No dependence Can produce physical Can produce physical No dependence
dependence dependence
Long term Possible: cognitive Cognitive difficulties Unknown Depression, memory No potential long term
sequelae deficiencies, brain (attention, learning, loss, mental confusion, neurotoxic effect
neurotoxicity memory) paradoxical agitation,
stomach disorders
Adapted from Chakraborty K, Neogi R, Basu D. Club drugs: Review of the 'rave' with a note of concern for the Indian scenario.
Indian J Med Res 2011;133:594-604.25
131
Scientific studies about the uses of these club drugs and their short-term and long-term
effects on animals have shown these drugs can be damaging in multiple ways, and some
drugs (particularly MDMA) can damage specific neurons in the brain5. Moreover,
routine drug screens do not pick up various club drugs, and gas chromatography-mass
spectrometry (GC-MS) testing must be requested to confirm the presence of the specific
drug, otherwise many cases of sexual assault and driving under the influence go
undetected. In this guideline we attempt to discuss the epidemiology, clinical
pharmacology, neurobiology, clinical and adverse effect profile, and treatment
strategies of club drugs with a section contributing to the Indian scenario.
1.2. SCOPE AND METHODOLOGY OF DEVELOPING THE GUIDELINE
The index guideline covers the epidemiology, clinical pharmacology, neurobiology,
clinical and adverse effects, and management of acute intoxication, harmful use,
withdrawal and dependence state due to use of club drugs wherever applicable. In
general the ICD-10 classification for mental and behavioural disorders was followed as
the point of reference. Mental and behavioural disorders due to use of hallucinogens
can be coded under F16 of ICD-10, whereas mental and behavioural disorders
associated with other club drugs can be coded under F19 (Mental and behavioural
disorders due to multiple drug use and use of other psychoactive substances).The
discussion on management mainly focuses on five types of club drugs which has already
been referred to in the previous section. The general principles in the management of
club drugs intoxication, harmful use, withdrawal and dependence are presented later in
this chapter. This guideline assumes importance because consistent treatment protocols
are lacking which the clinicians can follow when confronted with users of club drugs as
newer generation of youths are increasingly opting for these drugs to get the desired
'kick' particularly in club/ rave settings. In index guideline 'acute intoxication' means, a
transient condition following the administration psychoactive substance, resulting in
disturbances in level of consciousness, cognition, perception, affect or behaviour, or
other psychophysiological functions and responses; 'harmful use' means, a pattern of
psychoactive substance use that is causing damage to health, the damage may be
physical or mental; 'dependence syndrome' means, a cluster of physiological,
behavioural, and cognitive phenomena in which the use of a substance or a class of
substances takes on a much higher priority for a given individual than other behaviours
that once had greater value; and 'withdrawal state' means A group of symptoms of
variable clustering and severity occurring on absolute or relative withdrawal of a
substance after repeated, and usually prolonged and/or high-dose, use of that substance.
1.3. DATA SEARCH METHODOLOGY
The data search strategies for this review included electronic databases as well as hand-
search of relevant publications or cross-references. The electronic search included
PUBMED and other search engines (e.g. Google Scholar, PsychINFO). The data search

Club Drugs
strategies for this review included electronic databases as well as hand-search of

relevant publications or cross-references. The electronic search included PubMed and
other search engines (e.g. Google Scholar, PsychINFO etc.). Cross-searches of other
electronic (e.g., online newspapers and magazines) and hand-search of key references
often yielded other relevant material. The search terms used, in various combinations,
were: club drugs, rave drugs, recreational drugs, rave parties, Ecstasy, Ketamine,
Rohypnol, GHB, LSD, hallucinogens, street names, pharmacology, toxicology,
psychiatric disorders, guidelines and management. Much of the clinical evidence is
derived from review articles, individual case reports and case series and a small number
of prospective observational studies, retrospective audits and analysis of patient
records.
2. CLUB DRUGS
2.1. EPIDEMIOLOGY OF CLUB DRUGS
Despite evidence that suggests an increase in the population level use of these drugs,
research on the population prevalence of their use is limited, most probably because of
the relative recency of their recreational use. For Ecstasy the prevalence has been
estimated between 0.9% in France to 19.7% in Australia.26,27 The others are much less
prevalent - 0.9-4.7% and 0.7-2.6% for GHB and Ketamine respectively, depending
upon the population and age group studied.28-30 One study reported 20% of youths aged
16–23 having ever used one or more of these club drugs.31In the US, data from the
2011 National Survey on Drug Use and Health estimate that about 14.5 million
individuals aged 12 or older had used ecstasy at least once in their lifetime; about 2.4
million had used the substance at least once in the previous year; and about 540,000
were current users (defined as use during the previous month).32
The data on dependence potential of club drugs is relatively sparse. In a study of 400,
18- to 20 year old club going young adults, majority (58.5%) met the criteria for club
drug dependence.33 In a cross-nation study using the computerized Substance Abuse
Module for Club Drug (CD-SAM) 15% and 59% of the subjects met MDMA abuse and
dependence, respectively.34 Club drug toxicity is a common reason for presentation to
the emergency department from a nightclub environment.35-37 Wood et al.38 reported
that, out of 173 individuals with club drug toxicity requiring medical attention in a large
urban nightclub, the majority of individuals were frequent club drug users, and a
signi? cant proportion had recurrent club drug toxicity requiring assistance.
Some researchers have argued that men experience more opportunities to try drugs.39
However, it is likely that frequenting dance clubs, in which there are many
opportunities to experiment with drugs, may result in comparable opportunities for
females to initiate use and, thus, minimize prevalence differences across gender.
Meanwhile, young adult females have been found to be at the greatest risk of

experiencing harm from club drugs and to report negative consequences.40-41 Other
studies have not found gender differences in club drug use.33,42,43
Further, polysubstance abuse is common among users of club drugs, often used in
combination, particularly with marijuana or alcohol.31,44,45 In a survey of 23,780 middle
school students in New York City, it was found that Black students were less likely than
White students to useclub drugs. The use of alcohol and/or marijuana predicted club
drug use regardless of the timeframe of use, and lifetime cigarette use predicted lifetime
club drug use.46 It has been found that, club drug use is common among youths in
treatment for substance abuse and has spread beyond the rave culture.47 In a
retrospective review of 38,350 case records from 1998 through 2003 of persons
admitted with problems with club drugs were compared against users of alcohol or
other drugs. Club drug users were more impaired on ? ve of six Addiction Severity Index
(ASI) indices at admission and they were more likely to use multiple substances more
often. They were more likely than users of alcohol or other drugs to complete treatment,
but this varied by drug. At follow-up 90 days after discharge, club drug users continued
to report more ASI problems. Pro? les of these clients show that ecstasy use has spread
beyond the club culture, as indicated by the changes in client demographics over time.
GHB clients presented a mixed picture of severe problems at admission and good
response to treatment. Hallucinogen clients were young and less likely to complete
treatment.48
Much of the available literature on the epidemiology of “club drugs” among men who
have sex with men (MSM) derives from studies conducted on the west coast of the
United States (Reback and Grella, 1999; Lewis and Ross, 1995; Frosch et al., 1996),
with additional studies in Australia (Kippax et al., 1998) and Western Europe (Henry,
1992). 49-53 In a study of 569 MSM youths, recruited during 2000 and 2001, high rates of
lifetime exposure to a variety of club drugs(including methamphetamine, ketamine, and
MDMA) was observed. Among those who used club drugs on a chronic basis (N = 145),
there was high rates of a prior suicide attempt (including high rates of multiple suicide
attempts), high rates of lifetime exposure to multiple types of drugs, high rates of current
poly drug use (including multiple types of club drugs), and high rates of current
depressive symptoms.54 MSM who had ever used MDMA were more likely to report
unprotected anal sex and were more likely to be diagnosed with an STD than MSM who
had never used MDMA.55A study assessing the pattern of club drug initiation among
gay and bisexual men suggests that the sequencing of club drug use may be better
explained by socialization processes in the gay community than by Gateway Theory,
which has been traditionally used to explain patterns of drug use in the population.56
The epidemiological studies on club drugs are shown in Table 2.

Club Drugs
Table 2: Epidemiological studies on club drugs

Author Country Population Drug Percentage
Survey on "Drug affinity Germany Youth aged 12-25 Ecstasy 4%
among young people in years (MDMA)
the federal republic of LSD 2%
Germany"57
Kraus & Augustin58 Germany 18-59 year old MDMA 1.5%
LSD 2%
Tossmann& Heckmann59 Germany 1664 adolescents MDMA 44.4%
and young adults LSD and 37%
attending techno related
parties hallucinogens
Tossmann et al60 Germany 1412 young adults MDMA 40.1%
attending techno LSD and 33.6%
parties related
hallucinogens
Wilkins et al61 New 15-45 years MDMA 5.4%
Zealand Ketamine 0.7%
GHB 4.7%
Abraham et al62 Netherlands 15-64 years MDMA 3.6%
National Plan on Spain Household survey MDMA 4.2%
Drugs, 200163
Beck et al64 France 15-64 years old MDMA 0.9%
Centre for Addiction Canada, Students of MDMA 5.6%
and Mental Health65 Ontario grade 7-12 Ketamine 2.6%
GHB 1%
Aust66 United 15-59 years MDMA 5.9%
Kingdom
Australian Institute of Australia 14+ years MDMA 6.1%
Health and Welfare67
SAMSHA68 United 12th grade students MDMA 3.3%
States MDMA 15.1%
Johnston et al69 United 12-17 years MDMA 4.5%
States 18-25 years Ketamine 2.1%
GHB 1.4%
Gripenberg-Abdon Sweden 401 cruise ship MDMA+ 10.1%
et al70 passenger of a Amphetamines
40 hour electronic
dance music event
Havere et al71 Belgium 775 visitors of clubs, MDMA 19.1%
dance events, and
rock festivals
Seattle, USA 310 Rave party 74.19%
Banta-Green et al55 attendees MDMA

2.2. MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE or ECSTASY)

Ecstasy (also called X, M, E, XTC, rolls, beans, Clarity, Adam, lover's speed, hug drug) is
a synthetic, psychoactive drug with both stimulant and hallucinogenic properties
similar to methamphetamine and mescaline. MDMA was developed in 1914 as an
appetite suppressant, but animal tests were unimpressive, and it was never tested in
humans.23 In the 1970s and 1980s, MDMA was thought to be a useful adjunct to
psychotherapy due to the altered state of consciousness it produced.72 Despite the lack
of scientific evidence, the Multi disciplinary Association for Psychedelic Studies (MAPS)
is currently supporting the progression of research to investigate the effectiveness of
MDMA as a therapeutic adjunct to psychotherapy.73 It has been a Schedule I drug in
USA since 1985 having a high potential for abuse. There is no currently accepted
medical use of this drug in treatment in the USA, and there is a lack of accepted safety for
use of this drug under medical supervision.74 Prevalence has varied over time but data
from the Crime Survey for England and Wales (CSEW) shows that in 2013-14 it was the
third most prevalent illicit drug after cannabis and cocaine, with 1.6% of adults aged
16–59 and 3.9% of young adults(16–24 years) having used it in the last year.24 A multi
site study exploring the psycho economic factors of Ecstasy consumption has found that
monetary and opportunity cost, but not income, significantly predicted Ecstasy use.75 A
recent study has found that, low risk perception, high perceived behavioural control of
obtaining Ecstasy (an estimated Ecstasy procurement time less than 24h), and current
Ecstasy dependence predicted future Ecstasy use.76 Another study among young women
found that high stress level is positively correlated with ecstasy use and indulgence in
high risk sexual behaviour.77
2.2.1. Clinical Pharmacology
MDMA can be taken through various routes (Table 1). 25 Most tablets containing MDMA
are produced in clandestine laboratories in Belgium, Luxemburg, or in Asia. The
simplest method of manufacturing MDMA is through 3,4-methylenedioxyphenyl-2-
propanone (PMK), a commercially available ketone. Other common precursors include
saffrol, isosaffrol, piperonal, and safrole (often from sassafras oil).78 A review of surveys
on the contents of Ecstasy tablets found in the 1980s and early 1990s showed that the
ingredients of the “MDMA” sold as “esctasy” could include other psychoactive
substances as well.79 MDMA is being increasingly used in combination with ketamine
and selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, which
produces a rush initially, prolongs the pleasurable effect, and results in easier
comedown following a high.80,81
2.2.2. Neurobiology
The principle effects are on the serotonin system where it is an indirect serotonin
agonist. MDMA inhibits tryptophan hydroxylase, which decreases serotonin

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production.82 It induces the release of serotonin and also blocks serotonin re-
uptake.These effects are thought to be related to the observed depression, anorexia,
agitation, and marked feelings of empathy reported in association with use of the drug.
Because MDMA depletes serotonin stores in neurons, subsequent doses produce
diminished euphoria and increase adverse effects such as depression and agitation.83 In
addition to its effects on serotonin neurotransmission, MDMA has also been shown to
affect the noradrenergic, dopaminergic, and cholinergic neurotransmitter systems.6,84,85
Clinical effects of MDMA have been varied ranging from increased energy to
depression (Table 1).7-11 Partygoers are motivated primarily by the energetic and
euphoric effects they expect from MDMA.86 MDMA has been shown to increase energy
and psychomotor drive, self-con? dence, and well-being, and to produce a positive
mood, heightened sensory awareness (such as intensi? ed perceptions), derealization,
depersonalization, and to increase responsiveness toemotions and sense of closeness to
others.83 MDMA increases sexual arousal and there are reports where MDMA was
specifically used to increase the sexual vigour.87,88 No withdrawal syndrome from
MDMA has been reported.82 Regular ecstasy users often report diminished
responsiveness to the drug and a consequent need for dose escalation, both of which
imply the development of tolerance.32
Ecstasy use can also bring about a range of negative physical side effects while under the
influence of the drug and during the comedown period (Table 1)12-15. Adverse effects
include anxiety and thought disorder, jaw clenching (bruxism), lack of appetite,
difficulty concentrating, disturbance of balance, and an increase in blood pressure. In a
study of MDMA administration, some of these effects were still reported by some
subjects after 24 hours.9 Women reported more undesirable acute subjective effects
(e.g. physical illness, depressed mood, anxiety, thought disorder and perceptual
changes) with greater intensity relative to males.89 In addition, studies have found a
relationship between MDMA use (but not use of other drugs) and high risk sexual
behaviour (unprotected anal intercourse) among homosexual and bisexual men
attending dance clubs.55, 90
There are numerous reports of Ecstasy producing severe acute toxicity resulting in death
usually related to severe dehydration, strokes, hyperthermia, and hyponatremia.91
These cases involved seizures, tachyarrhythmias, hypertension, diaphoresis, and
pupillary dilation. In addition, body temperatures rangedfrom 104–110?F, which was
associated with a variety of complications including kidney failure and death. Evidence
of possible liver toxicity is also suggested as another severe outcome related to MDMA
use. MDMA ingestion directly causes a rise in antidiuretic hormone. Heat from the
exertion of dancing in a crowded room coupled with the MDMA-induced hyperthermia

can lead easily to excessive water intake and severe hyponatremia, to which young
women appear to be particularly susceptible.92,93 Cases have also been reported of
damage to the neurological system including cerebral infarctions and hemorrhage,
accompanied by neurological impairment. MDMA ingestionhas also been implicated
in the experience of psychiatric disturbances such as depression, panic attacks, and
? ash backs of hallucinations. It is likely that these disturbances emergein individuals
who are already “at-risk” for mental illness; however, it has been suggested that because
MDMA has demonstrated neurotoxicity it might actually be able to induce chronic
psychosis in the absence of such individual risk.83Long-term use of MDMA has been
related to brain neurotoxicity (lower density of serotonin transporter sites) even after
periods ofabstinence.94,95
There is also a substantial risk for fetal exposure from women who are, or become
pregnant, while using MDMA. Pregnant women who use MDMA tend to be young,
single, and report psychological morbidity and have a clustering of risk factors that may
compromise the pregnancy and fetus. Pregnant rats exposed to MDMA during a period
that was developmentally equivalent to the human ? rst trimester days had pups with
signi? cant neurochemical and behavioural alterations, which is the ? rst report of its
kind following a prenatal MDMA exposure.5,96
2.2.4. Management
Laboratory identification of MDMA is difficult. MDMA is excreted as unchanged drug,
3,4-methylenedioxyamphetamine (MDA), and free and glucuronidated/sulfated 4-
hydroxy-3-methoxymethamphetamine (HMMA), and 4-hydroxy-3-
methoxyamphetamine (HMA) metabolites.Identification of HMMA as well as MDMA
through gas chromatography-mass spectroscopy (GC-MS) increases the ability to
identify positive specimens but requires hydrolysis.97,98.
2.2.4.1. Management of acute MDM Atoxicity
The most common interventions requiredare clinical monitoring, observation and
reassurance, and symptomatic treatment, including ? uids (D).99 The average duration of
hospital stay reported by the Australian study was three hours (III).100 Dehydration
should be addressed. Following ecstasy-related presentation to a hospital emergency
department, intravenous ? uids were administered to 31% of patients in a UK study,130
and to 71% of cases in a Swiss study, but it is important to note that symptoms following
ecstasy use range from severe dehydration to severe hyponatraemia; the latter patients
require ? uid restriction, so it is dangerous to give hypotonic ? uids or normal saline to
patients prior to proper assessment (III).101,102 There is no evidence to support gastric
decontamination with activated charcoal, but it may be appropriate for cases of
presentation within 1 hour of ingestion (IV).24

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Patients presenting with body temperatures above 39° C need aggressive

coolingmeasures, such as ice baths or internal cooling, and benzodiazepine sedation
(IV).24 It has been suggested that dan trolene may be considered when hyperthermia
persists. However, this has been contested by some. No clinical trials have been
conducted but a review has reported better survival rates for patients with temperatures
above 40°C who received dan trolene, with minimal adverse effects (III).103 Referral to
an intensive care unit may need to be considered for monitoring and ventilation (IV).24.
Recommendations:
l In acute MDMA toxicity short period of hospital stay is recommended (C)
l Severely dehydrated patients may require intravenous fluid (C)
l Patients with severe hyponatremia may require fluid restriction (C)
l Gastric decontamination with active charcoal is indicated if presentation is within 1
hour of ingestion (D)
l Hyperthermia can be treated with Dantrolene (C) or benzodiazepine sedation (D)
2.2.4.2. Management of harmful use and dependence of MDMA
The treatment of harmful ecstasy use is primarily psychosocial. Nospeci? c guidelines
for psychosocial intervention have been described and validated forchronic ecstasy
users. For those that do seek help, typical treatment approaches include individual and
group counselling, cognitive behavioural therapy, and relapse prevention technique.104
Recommendations:
l Psychosocial treatment is the mainstay for chronic harmful use of MDMA (D, S)
2.3. KETAMINE
Ketamine, a derivative of phencyclidine, is an anaesthetic that has been approved for
human and animal use, both in trauma and emergency surgery as well as veterinary
medicine. Illicit ketamine is also known as Special K, Vitamin K, K, kit-kat, keets, super
acid, super K, cat valiums and jet.It can be taken through various routes (Table 1). 16 A
typical method uses a nasal inhaler, called a “bullet” or “bumper”; an inhalation is
called a “bump”. Ketamine often is taken in “trail mixes” of methamphetamine, cocaine,
sildenafil citrate (Viagra), or heroin.105 Both popular and research accounts indicate that
the recreational use of ketamine has widened in the context of nightclubs, dance parties,
and raves.106 Cases of Ketamine dependence have also been reported among
anesthesiologists who have easy access to the agent.107,108 Leung et al.109 conducted a
focus group with club drug users and noted that there was a special drug use sequence
widely practiced by Taiwanese poly-drug users. In a single drug use episode, MDMA
was usually the first drug used, followed by ketamine and then marijuana. This unique

sequence of polydrug use in a single episode is called “Trinity”.110 Chinese Severity of

Dependence Scale for Ketamine (C-SDS-K) has been found to be a reliable and valid tool
for measuring the severity of dependence in the treatment-seeking population of
Chinese ketamine users.111
Koesters et al.112 brie? y reviewed reports of the uses of ketamine for human anaesthesia,
indicating that its use was associated with hallucinations after waking up, which led to
discontinuation of ketamineas an anesthetic agent in humans. Recently there has been
renewed interest in its use as an anesthetic agent in brief painful procedures. Ketamine is
a potent analgesic which prevents 'wind-up', where neurons in the spinal cord become
sensitized to painful stimuli.113 In this way, low doses of ketamine given before, during
and after surgery improves post-operative pain relief. In humans low doses (0.1–0.5
mg/kg/hour) of ketamine can be used as local anaesthetics and co-analgesics, and are
particularly effective for neuropathic pain114 which is notoriously dif? cult to treat. Low-
dose ketamine is also effective in treating complex regional pain syndrome.115,116
Intravenous Ketamine is now being increasingly used for treatment of refractory
depression in the dose of 0.5 mg/kg as a slow intravenous infusion.117,118 Intravenous
Ketamine also has short lasting effect on suicidal cognition of depressed patients.119
Ketamine is a Schedule III controlled substance in USA whereas in India it is placed
under Schedule H. Ketamine is a well-known immune modulator and, as for most club
drugs, it behaves as an immunosuppressive drug.120 Anaesthesia doses are 2-10 mg/kg
while recreational doses can range between 50–100 mg.112 Frequent users often take
ketamine in a pattern of cyclical binges similar to cocaine or amphetamine dependence.
Tolerance builds rapidly and can be very high.121 Users can become psychologically
dependent, with craving and a high tolerance.121,122 Ketamine withdrawal symptoms
characterized by anxiety, shaking, sweating, palpitations and carvings seem to be key
problems in frequent ketamine users and have been published by many case
studies.110,123-125.
2.3.2. Neurobiology
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. It binds to the same
NMDA receptor site as phencyclidine, located in the calcium channel, leading to a
blockade in calcium flow through these channels. Decreased excitatory amino acid
neurotransmission mediated by NMDA receptors through calcium channel blockade
has been associated with altered perception, memory, and cognition.126 NMDA
blockade is associated with increased dopamine release in prefrontal cortex and
midbrain. It has also been suggested that ketamine, through its binding to the NMDA
receptor, can inhibit the reuptake of serotonin, dopamine, and norepinephrine,
although the mechanism underlying this action is not entirely clear.14

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When misused, subjective experience depends on the dose of the drug consumed
(Table 1) 1,16,17,19,20. Acute adverse effects are many (Table 1). These include increased
heart rate, hypertension, impairment of motor functioning, respiratory depression,
nausea, immobility that leads to abnormally low body, temperature, anxiety,
dissociation, depression, recurrent ? ash backs, delirium (confusion disordered speech,
hallucinations), amnesia, impaired attention, learning disability, and symptoms of
schizophrenia. Effects due to chronic misuse include cognitive difficulties in areas such
as attention, learning, and memory.17 Taffe et al.127 concluded that recreational exposure
to sub anaesthetic doses of ketamine was likely to induce wide-ranging compromise of
cognitive function ranging from memory to attentional to motor domains. In another
cross-sectional study, frequent users of ketamine displayed impairments in working and
episodic memory and executive functions and experienced reduced psychological
wellbeing.128 A neuroimaging study by Liao et al.129 has found white matter changes in
bilateral frontal and left temporoparietal cortices. There was also evidence that frontal
white matter fractional anisotropy correlated with the severity of drug use.
When misused, low doses are associated with feelings of relaxation called “K-land,”
while higher doses can produce dreamlike states, hallucinations, visual distortions, and
sensation of near-death experience called a “K-hole”.1,16 Its use has also been associated
with unintentional injuries that can occur because the user is insensitive to pain.1 In
addition it has been associated with sexual assault because of its dissociative effect in
humans.83 There are very few deaths by “pure” ketamine overdose recorded. Of 87
ketamine-linked deaths in New York City, none was purely due to the use of
ketamine.130 Parke-Davis has reported that there are cases of accidental injections with
10 times the amount required for surgery, with no obvious, lasting effects.131
Ketamine withdrawal symptoms characterized by anxiety, shaking, sweating,
palpitations and carvings seem to be key problems in frequent ketamine users and have
been published by many case studies.123-125.
2.3.4. Management
Ketamine is not tested for in standard or advanced drug tests. It is not included on the list
of drugs the Substance Abuse and Mental Health Services Administration (SAMHSA)
uses for employee drug testing purposes. However if a specific test was requested,
norketamine, the breakdown product of Ketamine, is detectable in blood and urine for
7-14 days and "sometimes far longer" in heavy users through high performance liquid
chromatography (HPLC).14,94.
2.3.4.1 Management of acute toxicity of Ketamine
The diagnosis of ketamine should be considered when people (especially young

people) present with agitation, tachycardia and either visual hallucinations or

nystagmus, although the absence of the latter two ? ndings does not rule out the
possibility of ketamine misuse. No antidote exists for ketamine overdose. Activated
charcoal is not necessary after ketamine acute intoxication, unless there is evidence that
a co-ingestant may be contributing to the patient's symptoms or, in thecase of a large
ingestion, if the patient presents very early (IV).24
Although randomised controlled trials and other robust studies are not available, there
is consistency in case reports and series that patients are best managed with standard
supportive care, with special attention to cardiac and respiratory functions, as the effects
of the drug are usually short-lived (IV).132,133 Benzodiazepines can be used for agitated
patients (IV).24 Patient should be kept in a quiet environment, with minimal external
stimuli which prevents excessive agitation (IV).24 Profoundly obtunded patients may
require airway support, intravenous ? uids and titrated benzodiazepine therapy if they
are agitated, hyperthermic or show overt sympathomimetic signs (IV).134
Recommendations:
l Supportive care with special attention to cardiac and respiratory function is the
mainstay of treatment (S)
l Patient should be kept in a quiet environment with minimum external stimulus (S)
l Activated charcoal can be used in the presence of co-ingestant or if the patient
presents very early (D)
l Benzodiazepines cane be used for agitated or hyperthermic patients (D)
2.3.4.2. Management of Ketamine dependence and withdrawal
A small number of ketamine-speci? c psychosocial studies have also been conducted.
Copeland et al.135 suggest that the harms that require further investigation are the
association of ketamine use with unsafe sex and injecting behaviours and its neurotoxic
effects. Effective brief and early interventions are needed for those who are at risk of
harm because of ketamine intoxication and/or excessive and regular consumption (IV).
Critchlow described the treatment of a person with dependence on ketamine that
involved three motivational interviewing sessions in the ? rst instance (IV).136 An
abstinence-oriented approach can be used for ketamine, similar to that used for
psychostimulants (IV).137
Only one case report of ketamine withdrawal is available and describes medically
assisted detoxi? cation carried out in conjunction withthree sessions of motivational
interviewing. Detoxi? cation was carried out usinga reducing regimen of diazepam over
three days. The regimen was successful and eliminated the majority of withdrawal
symptoms (IV).136

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Recommendations:
l Psychosocial treatments are mainstay of ketamine dependence (D)
l Ketamine withdrawal can be treated with tapering dose of diazepam modified from
alcohol detoxification regimen (D)
2.4. GAMMA-HYDROXYBUTYRATE (GHB)
GHB is available as a clear liquid, white powder (dissolved in water), tablet, or capsule
and can be made in private residences with ingredients and recipes obtained on the
Internet (DEA 04). Street names include “G”, “Liquid Ecstasy,” “Scoop,” “Easy Lay,”
“Georgia Home Boy,” “Grievous Bodily Harm,” “Liquid X,” “Goop,” “Gib,” “Soap,”
“Blue Nitro”, “Blue Verve”, “Caps”, “Chemical X”,“Cherry Meth”, “Date Rape Drug”,
“Drogue du Cambriolage Sexuel Parfait”, “Ellie”, “Ever Clear”, “EZ Lay”, “Fantasy”, “G”,
“Gamma-OH”, “Get-her-to-Bed”, “Great Hormones at Bedtime”, “Grievous Bodily
Harm”, “G-Riffic”, “Jib”, “Liquid Dream”, “Liquid E”, “Liquid Ectasy”, “Liquid G”,
“Liquid X”, “Liquid-XTC”, “Natural Sleep 500”, “Organic Quaalude”, “Salty Water”,
“Scoop”, “Scoop Her”, “Sleep”, “Soap”, “Somatomax”, “Somatomax PM”, “Vita-G”,
“Water” and “Nitro”.23.
GHB was suggested for medical use in anaesthesia, obstetrics, and psychiatry138
(including possible use for alcohol and narcotic withdrawal symptoms) in the 1960s and
also in the treatment of alcohol and opiate withdrawal, fibromyalgia, and
narcolepsy.23,139-142 By the 1990s, GHB was being marketed for illicit use in weight
control management and its purported anabolic properties and associated muscle
growth that made it a popular drug with body builders.6,14 In addition, GHB has been
implicated for its use in association with sexual assault because victims have difficulty
resisting the assault due to the level of intoxication produced. The associated memory
problems and the fact that it clears from the body quickly (within 12 h) make detection
difficult and increase the complexity of attempts to prosecute for which GHB derived its
infamous label of 'date rape' drug.16 Much interest has been generated regarding driving
difficulties caused by GHB. In has been found that, two symptoms that most commonly
caused driving difficulties were rapid loss of consciousness or onset of stupor, known
among users as “G-napping” and periods of anterograde amnesia.24 GHB is now a
Schedule I drug in the U.S. and Schedule IV of the 1971 UN Convention. In 2002,
sodium oxybate, a formulation of GHB, was approved for the treatment of narcolepsy
and classified as schedule III.23
Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid occurring naturally in
mammals. GHB can form salts (e.g. sodium and potassium salts), which are soluble in
water and alcohol. It is colourless and easily mixes in aqueous solutions; however, a

salty taste may be noticeable.143 Illegal GHB and its precursors, GBL (gamma
butyrolactone) and 1,4-BD (1,4-butanediol), can be obtained over the Internet and
sometimes are marketed as solvents such as ink jet printer fluid or as GHB alternatives in
health food stores, gyms, raves, and nightclubs. GHB and GBL are subject to
interconversion in aqueous media.
GHB pharmacokinetics have been studied in healthy volunteers, narcoleptics,
alcoholics, and patients with liver impairment. A further study monitored GHB kinetics
following 1,4-butanediol administration to healthy volunteers. When healthy adult
volunteers and patients with biopsy-proven liver cirrhosis were compared, there was a
marked reduction in clearance following oral administration and significant
prolongation of elimination half-life.144 GHB is metabolized via succinic acid and the
citric acid cycle (TCA cycle/Krebs cycle), ultimately producing carbon dioxide and
water. GHB conversion to succinic semi-aldehyde can be catalysed by cytosolic GHB-
dehydrogenase or mitochondrial GHB-etoacid transhydrogenase. At low doses, GHB is
eliminated through the respiratory system, with higher doses via renal clearance. While
the half-life of GHB is short after low doses, high doses (such as those associated with
overdose) result in slow and prolonged absorption and a much longer half-life in animal
studies.23 The related chemicals, 1,4-BD and GBL, are metabolized endogenously to
GHB. 1,4-BD is metabolized by alcohol dehydrogenases to gamma-
hydroxybutyraldehyde and then by aldehyde dehydrogenase to form GHB; ethanol can
inhibit this metabolism as it acts as a competitive substrate to alcohol dehydrogenase.
Less than 2% of GHB is eliminated unchanged through urine. GBL is converted to GHB
by serum lactonase; this enzyme is not present in brain tissue.145, 146 Following the oral
administration of 1,4-BD 25 mg/kg, the mean elimination half- life was reported to be
about 39.3 minutes in healthy adult volunteers.147
2.4.2. Neurobiology
GHB acts as a neurotransmitter or neuromodulator and bind to GABA-B receptors; GHB
is both a metabolite and a precursor of the inhibitory neurotransmitter
gammahydroxybutyrate (GABA), and acts as a neuromodulator in the GABA system.23
GHB does not readily pass the blood brain barrier. The highest density of these
receptors is in the hippocampus, cortex, and dopaminergic areas (striatum, olfactory
tracts, and substantia nigra). GHB inhibits dopamine release and activates tyrosine
hydroxylase, that together act to increase central dopamine levels, which could be
associated with the reinforcing effects of GHB.148
Clinical and toxic effects of GHB can be found in Table 1.2,16,22 The symptoms typically
occur within 15-45 minutes, and resolve within a relatively short interval of time; CNS

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depression usually persists for 1-3 hours with patients making a complete recovery
typically within 4-8 hours. Other common neurological effects include ataxia,
disorientation, dizziness, confusion, hallucinations, somnolence, slurred speech,
dysarthria, confusion, headache, incoordination, euphoria, amnesia, hypotonia,
hyporeflexia, tremor, and myoclonus. Seizures or seizure-like activity have also been
reported agitation, bizarre behaviour, and combativeness has been noted in some
patients, either at presentation to the treatment facility or upon wakening. Patients can
also alternate between agitation and somnolence.
Table 3: Clinical effects of GHB at different doses
Dose range Clinical effects
10 mg/kg Short-term anterograde amnesia, hypotonia, and euphoria
20 – 30 mg/kg Drowsiness, sleep, and myoclonus
50mg/kg Coma
>50mg/kg Coma, bradycardia, and/or respiratory depression
Other less common neurological effects may include bruxism, vertigo, disinhibition,
increased sexual arousal, delusions, extrapyramidal side effects, dystonias, and athetoid
posturing. Miosis is common while mydriasis and horizontal and vertical gaze
nystagmus may also occur. Pupils may also be sluggish or nonreactive. Common
cardiovascular effects include bradycardia, and hypotension. Chest tightness or
palpitations may also occur. The major respiratory effects of GHB include dose-related
respiratory depression, bradypnoea, periodic (Cheyne-Stokes) respirations, and apnoea
and respiratory failure. Metabolic features include hyperglycaemia, hypokalaemia, and
potentially hypernatremia if large doses of the sodium salt are ingested. Elevated
creatine kinase activity/rhabdomyolysis may also occur. Nausea and vomiting are
common gastrointestinal symptoms following oral or intravenous administration of
GHB. Death is normally due to respiratory failure. GHB use alongside other CNS
depressant drugs may increase toxicity by producing synergistic CNS depression. and
co-ingestants may also contribute to fatalities involving GHB.21,147
The Drug Enforcement Administration (DEA) has documented deaths related to GHB.15
Several issues to note were the presence of other substances (particularly alcohol and
opiates e.g. heroin, codeine, dihydrocodeine and morphine); the presence of GHB in
postmortem blood specimens, in cases where there has been no evidence of GHB use
and the GHB concentration found is sometimes low despite the user dying due to GHB
use.
Dependence on GHB has been described as developing after regular use, i.e., every 2h
round-the-clock for 2 months to 4 year.23 Withdrawal symptoms include insomnia,

muscular cramping, tremor, perspiration, anxiety, and feelings of doom.149 Withdrawal

from higher doses includes bowel bladder incontinence and blackouts.148
2.4.4. Management
2.4.4.1. Management of acute GHB toxicity
A diagnosis of GHB intoxication is typically made on the basis of the patient's history
and presentation. However, as such symptoms are not specific, it may be difficult to
differentiate GHB poisoning from other sedative hypnotic intoxications, especially if no
history of GHB use is available to the clinician. GHB is detected by routine urine screens
in the western countries which are not available in India now, but other immunoassays
for GHB and GBL are not available. These are reliably detected by specific requests for
GC-MS, but timing is important, as GHB is rapidly excreted as carbon dioxide through
exhalation.21 GHB has a half-life of 27 min and it is virtually undetected in the urine 12 h
after ingestion.133 Since GHB continues to be produced after death, it should be
collected in tubes containing sodium fluoride.150 In cases of chemical submission, both
urine and blood should be analyzed, since GHB is present longer in urine than in blood,
and a detailed case history should be obtained. A sensitive and specific GC-MS method
using selective ion monitoring has been developed for the quantification of GHB in
blood.151
Decontamination is unlikely to be beneficial in the majority of cases because of the
drug's rapid absorption, particularly when consumed in a liquid form. Activated
charcoal (50-100 g) should only be considered in patients who are alert, stable, and
cooperative, or have a protected airway (IV).152,153 Supportive care is the mainstay of
management, with primary emphasis on respiratory and cardiovascular support. Initial
treatment includes securing intravenous access and continuous cardiac and blood
pressure monitoring along with pulse oximetry and arterial blood gas monitoring.
Airway protection including rapid sequence induction with endotracheal intubation
and/or assisted ventilation is indicated (IV).24 Atropin may be needed for patients with
haemodynamically unstable hypotension which is treated with crystalloids (IV).24
Myoclonic movements typically do not require any specific treatment but
benzodiazepine administration may be useful (IV).24 Seizures may be treated with
lorazepam or diazepam only if the patient has seizures and is well ventilated (IV).24
There are no specific antidotes for GHB poisoning. However, some pharmaceuticals
have been investigated as potential antidotes.147 They are Physostigmine, Naloxone,
Flumazenil and GABA-B antagonist, SCH 5091.147
Recommendations
l Supportive care is the mainstay of treatment. Endotracheal intubation may be
required if vomiting is present (D,S)

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l Decontamination with activated charcoal should be considered in patients who are

alert, stable and have a protected airways (D)
l Atropine can be used for hemodynamically unstable patients (D)
l Myoclonic movements and seizures may be treated with lorazepam or diazepam (D)
2.4.4.2. Management of GHB withdrawal
The GHB-related withdrawal syndrome seems consistent with other hypnotic/sedative
withdrawal syndromes. Commonly reported symptoms include auditory and visual
hallucinations, tremors, tachycardia, hypertension, sweating, agitation, anxiety,
paranoia, insomnia, disorientation, confusion, and aggression/combativeness. Patients
may also suffer depression, miosis, nystagmus, cardiac palpitations, dyspnea,
tachypnoea, nausea and vomiting, diarrhoea, and abdominal pain, though this is less
common. Withdrawal can occur rapidly following the last dose taken by the user; in one
case series, it developed within 1-12 hours. The duration of these clinical effects may
continue for three to twenty-one days.23 In severe cases, delirium, psychosis,
rhabdomyolysis, and seizures, are observed which may become life-threatening.
To date, there have been no rigorous prospective clinical trials investigating GHB
withdrawal treatments. Combined evidence suggests that benzodiazepines are the ? rst
line of treatment, but adjuncts may be helpful to control symptoms (IV).154 Baclofen and
barbiturates have been described as second-line adjuncts.24 TOXBASE recommends
that withdrawal symptoms can be effectively treated with a combination of diazepam
and baclofen and this has been used successfully in clinical practice, as part of
medically assisted detoxi? cation (IV).152,155-158 A wide range of medications have been
used and described as potentially helpful in GHB withdrawal management. However,
supporting evidence for any of these medications is mainly based on a small number of
case reports and case series. These agents include barbiturates, valproic acid,
carbamazepine, gabapentin, chloral hydrate, baclofen, clonidine, paroxetine, beta
blockers, bromocriptine, trazadone, fentanyl, propofol, or antipyschotics (IV).24
Recommendations
l Benzodiazepines are the first line of treatment for GHB withdrawal (D)
l Baclofen and barbiturates can be used as second-line adjuncts (D)
l Valproic acid, carbamazepine, gabapentin, chloral hydrate, baclofen, clonidine,
paroxetine, beta blockers, bromocriptine, trazadone, fentanyl, propofol, and
antipyschotics have been tried sporadically (D)
2.4.4.3. Management of GHB dependence
General psychosocial interventions for the use of club drugs are applicable to the
management of the chronic harms of GHB use, as well as aftercare and support (IV). 24

Recommendations
l Psychosocial interventions are the mainstay of treatment of GHB dependence (D)
2.5. FLUNITRAZEPAM
Street names of Flunitrazepam include Roofies, Rophies, Roche, Forget-me Pill, Circles,
Mexican Valium, Rib, Roach-2, Roopies, Rope, Ropies, Ruffies, Roaches, Circles,
Forget Pill, LA Rochas, Lunch Money, Mexican Valium, Mind Erasers, Poor Man's
Quaalude, Pingus, R-2, Roches, Roofies, Roopies, Rope, Rophies, Ruffies, Trip-and-
Fall, Whiteys, Forget me drug, Reynolds, Rolpes, Reffies, Ruffles, Sedexes, wolfies.23,159
Flunitrazepamis a benzodiazepine manufactured by Roche Laboratories, is available in
more than 60 countries in Europe and Latin America for preoperative anaesthesia,
sedation, and treatment of insomnia. In the United States where it is not legally
available, imported Flunitrazepamcame to prominence in the 1990s as an inexpensive
recreational sedative and a “date rape” drug.160It is odourless and tasteless and is easily
dissolved in beverages, allowing a perpetrator to add it to the beverage of a potential
victim. Flunitrazepam has had a long history of abuse by heroin and cocaine addicts.
The manufacturers, Hoffman-La Roche, are now adding a blue dye to the pill that will be
visible if added to a beverage though the generic flunitrazepam available in the grey
market do not have the dye.159
Flunitrazepamcomes in pill form and is typically taken orally, although reports of it
being ground and snorted are also available. Users swallow or chew the tablets or allow
them to dissolve under the tongue. The act of adding such substances to drinks is known
as "drink spiking". They also crush pills and snort the powder to feel the effects more
quickly, the powder can also sprinkled on marijuana and smoked or dissolved and
injected. Users feel the effects 15-20 minutes after ingestion, and they may last for 12 or
more hours.159
In 1996, the U.S. government prohibited the import of the drug, but it remains available
in other countries and continues to be illegally brought into the U.S. Since 2001, only
the 1mg Roche tablet has been available, although generic products continue to be
available in the 2mg strength, which has been the strength preferred for misuse, since
word around the street and in the sub-culture maintains that the 2mg pill produces a
quicker and a better “high” than two 1mg pills.161 Although the generic/grey market pills
may be white and round, the original manufacturer has reformulated the 1mg pill to be a
greyish-green oval tablet.
Chemical formula and structure of Flunitrazepam is C16H12FN3O3-5-(2-
Fluorophenyl) 1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepine. It is a white solid,

Club Drugs
with a melting point of between 166-167°C, a molecular weight of 313.3, and is soluble
in ethanol.159
2.5.2. Neurobiology
Similar to other benzodiazepines, Flunitrazepam is a GABA agonist. As such, it
mediates inhibitory neurotransmission in the brain and spinal cord.162 Benzodiazepines
bind to the GABA receptor, opening the chloride channels of neurons and resulting in
an influx of chloride and hyperpolarization of the cell. This decreases the excitability of
the cell producing sedation, anticonvulsant activity, and anxiety reduction.162
Clinical effects of Flunitrazepam are similar to benzodiazepines.23 The effects are much
greater with the concurrent ingestion of alcohol or other sedating drugs.23
Flunitrazepam has been suggested to have a higher abuse liability than other
benzodiazepines.163 Clinical effects of Flunitrazepam include disinhibition, amnesia,
and muscle relaxation, but individual effects vary.164 The amnesia is commonly of
anterograde type, that is, it involves memory loss for events that occur after the
medication is taken.23
Adverse effects of Flunitrazepam include decreased body temperature and blood
pressure, sedation, cognitive & psychomotor impairment, visual disturbances,
dizziness, confusion, GI disturbances, urinary retention.23 The effects of Flunitrazepam
can be felt within 30 minutes of being drugged and can last for several hours. If an
individual is drugged, he/she might look and acts like someone who is drunk.
Flunitrazepam overdose may result in excessive sedation, impairment of balance and
speech, and may progress in severe overdoses to respiratory depression, coma, and
possibly death.162
Cessation of Flunitrazepamuse can result in benzodiazepine withdrawal syndrome.
The withdrawal syndrome includes headache, tension, anxiety, restlessness, muscle
pain, photosensitivity, numbness and tingling of the extremities, and increased seizure
potential.165 Gradual discontinuation may result in withdrawal symptoms including
seizures, psychosis, severe insomnia, amnesia, loss of concentration, rebound
insomnia, mood swings, depression and severe anxiety. Abrupt and rapid
discontinuation may result in suicidal or homicidal ideations, mania, delirium,
convulsions, violence, catatonia and coma. As withdrawal weans off over days to weeks
patients often find that their physical and mental health improves with improved mood
and improved cognition.162
2.5.4. Management
2.5.4.1. Toxicology and detection
While a standard component of most urine drug screens is testing for benzodiazepines,

Flunitrazepam is administered in such small amounts and distributed so rapidly that

detection methods commonly fail. Typical toxicological tests can only detect
Flunitrazepamin blood and urine for up to 72 h after ingestion due to quick metabolism
and elimination.5 Laboratory identification of Flunitrazepam is very difficult to achieve
due to only a 72 hour period of time to test for it before the drug is metabolized in the
body. There are only insignificant traces after that time which is nearly impossible to
detect. Flunitrazepam is not detected with routine toxicological screening. After
ingestion it can be found in the blood stream for 24 hours and in urine samples for 48
hours. A sensitiveurine test can detect the presence of Flunitrazepam up to 60 hours
after ingestion. Flunitrazepam and its active metabolite 7-amino-flunitrazepam may be
detected by gas chromatography/mass spectrometry testing up. Hairs can also be used
as a possible source of detection of Flunitrazepam and its metabolites.159
Rohypnol Rapid Drug Test (Benzodiazepines Dip Test)–Flunitrazepam Urine Drug test,
a simple one step dip and read urine test card for detection of Benzodiazepines in urine.
This test card detects presence of Flunitrazepam in urine.
Micro-Plate Enzyme Immunoassay- Micro-plate enzyme immunoassay method allows
to detect Flunitrazepamand related compounds in urine at least up to 5 days after
administration of a single dose of Flunitrazepam (like in drug-facilitated sexual assault
scenarios). This significant increase in the detection time interval is possible if the
enzymatic hydrolysis of urine and solid-phase extraction is applied.159,166
Mass Spectrometry - Application of mass spectrometry with negative ion monitoring
chemical ionization allows detecting 7- aminoflunitrazepam, major metaboliteof
Flunitrazepam, in urine 14 days after administration of a single dose of Flunitrazepam.
The maximum concentration of 7-aminoflunitrazepam in urine was observed 6 to 24
hours after administration of a single dose of Flunitrazepam. The concentrations of 7-
aminoflunitrazepam in hair are much higher than concentrations of the parent drug,
Flunitrazepam. The metabolite remains in hair for at least one month after
administration of a single dose of Flunitrazepam.159,166
2.5.4.2. Management of Flunitrazepamintoxication/dependence
Management of Flunitrazepamover dose/dependence is similar to other
benzodiazepine overdose/dependence which has been elaborately dealt in the
previous volume of IPS-CPG which provided the guidelines for the management of
sedative-hypnotic use disorders.167 Supportive measures include use of activated
charcoal to absorb drug in the gastrointestinal tract as well as respiratory support (IV).165
Flumazenil is a specific benzodiazepine antagonist that may be administered to reverse
the effects of Flunitrazepam toxicity (IV).165

Club Drugs
Recommendations
l Decontamination with activated charcoal is done for patients with secured airways
and who present early (D,S)
l Flumazenil can be used to reverse the effects of Flunitrazepamtoxicity (D)
l Flunitrazepamdependence is managed by titrating doses of long acting
benzodiazepines similar to other benzodiazepine dependence (D)
l Psychosocial interventions are also useful for Flunitrazepam dependence (D)
2.6. LSD AND RELATED HALLUCINOGENS
LSD is the best-known synthetic hallucinogenic drug among the class of the
hallucinogens. Although LSD does not occur in nature, a similar analogue, lysergic acid
amine (LSA), is found in seeds of Argyreia nervosa and Ipomoea violacea used in Central
America for ceremonial purposes.168 Synthesized by Hofmann in 1938, LSD's
consciousness-altering properties were discovered accidentally a few years later. 169 Its
molecular structure and mechanism of action present similarities with serotonin, which
prompted the evaluation of its potential therapeutic use in alcoholics and patients with
mental disorders.170 In 1966, LSD was banned and in 1970 was reclassified as a
Schedule I controlled substance in an attempt to avoid its growing recreational use.171
The most common hallucinogenic fungi containing tryptamine derivatives are the
Psilocybe spp. mushrooms, which are widely distributed around the world, being
extremely used by indigenous people for centuries in sacred rituals, especially in South
American countries (particularly in Colombia), Mexico, India, Japan, New Guinea and
Australia.172,173,174 Psychoactive mushrooms soon became known worldwide as 'magic
mushrooms' and have turned famous among recreational users in the USA, Europe and
Japan. Psilocybe mushrooms, psilocybin and psilocin are classified as Schedule I drugs
in the USA, although the spores of mushrooms remain legal except California.168
Another very commonly known and used natural tryptamine is bufotenine or 5-
hydroxy-N,N-dimethyltryptamine (5-OH-DMT), an N-alkylated derivative of serotonin
and also a structural isomer of psilocin.175-178
LSD and other related hallucinogens are summarised in Table 4.

Table 4: LSD and related hallucinogens (Adapted from NEPTUNE, 2015)24
Chemical name Abbreviation Street products and names

(6aR,9R)-N,N-diethyl-7-methyl- LSD 'Acid', 'A tab', 'Blotter' (LSD on blotting paper
4,6,6a,7,8,9-hexahydroindolo- squares, ~1 cm2), 'Geltabs', 'Windowpane' (LSD
[4,3-fg]quinoline-9-carboxamide in gelatine squares/ pieces), 'Microdots' (very
(N,N-diethyl-D-lysergamide) small pills)
(8β)-9,10-didehydro-6- LSA (ergine) 'Morning Glory seeds' and 'Hawaiian Baby Wood
methylergoline- rose seeds' (seeds containing LSA and other
8-carboxamide alkaloids)
Other LSD related compounds ALD-52, ETH- 'Morning Glory seeds' and 'Hawaiian Baby Wood
LAD, PRO- rose seeds' (seeds containing LSA and other
LAD, AL-LAD, alkaloids)
LSZ
O-phosphoryl-4-hydroxy- Psilocybin 'Magic mushrooms', 'Mushies' or 'Shrooms'

N,Ndimethyltryptamine contain psilocybin and related tryptamines
4-hydroxy-N,N- Psilocin 'Liberty caps' or 'Libs' are the most common wild
dimethyltryptamine UK species of magic mushroom,
Psilocybesemilanceata. Also occurring in the UK
are Panaeoluscinctulusand 'Wavy caps',
Psilocybecyanescens'Cubes' or 'Boomers' are the
most commonly home-cultivated species,
Psilocybecubensis'Truffles' or 'Philosopher's
stones' are cultivated nodular growths (technically
'sclerotia') from other Psilocybespecies.
N,N-dimethyltryptamine DMT 'Dimitri' and 'Spice' are terms sometimes used for
the white, yellow or brown DMT crystals or
powder, often used for smoking (technically
vapourising). This should not be confused with
'spice' also commonly used for synthetic
cannabinoids. 'Ayahuasca' and 'Yagé' are
decoctions that include a DMT-containing
plant and another plant containing a monoamine
oxidase inhibitor, which allows DMT to be orally
bioavailable
alpha-methyltryptamine α
MT ‘AMT'
N,N-diisopropyltryptamine DiPT ‘Foxy'
5-methoxy-N,N- 5-MeO-DiPT ‘Foxy Methoxy'

diisopropyltryptamine
3,4,5- Mescaline 'Hallucinogenic cacti' contain psychoactive

trimethoxyphenethylamine alkaloids, principally mescaline. 'Peyote', 'San
Pedro' an 'Peruvian Torch' are the common
names for the three predominant species

Club Drugs
Chemical name Abbreviation Street products and names

2C Series, and their derivatives 2C-B has ‘Bees' are tablets or capsules containing 2C-B.
various close 'Nexus' is also 2C-B 'Tripstasy' was 2C-T-7, but
analogues; could be used for any drug combining
bk-2C-B, and hallucinogenic effectswith MDMA-like effects 'N-
25B-NBOMe Bomb' drugs are the NBOMe analogues series, so
25I-NBOMe may also be called 'NBOMe 2C-I'
Hallucinogenic DOM, DOI, 'STP' (for 'serenity, tranquillity and peace') was
amphetamines,DOx series and DOB, TMA-2 the original name for pills of DOM
their derivatives
Tetrahydrodifranyl compounds 2C-B-FLY, They are called 'FLY' because their molecular
bromodragonfly structure resembles the insect

In general, classical hallucinogens can be divided into two main structural classes:
1. Phenylalkylamines
2. Indolamines.
The chemical backbone of hallucinogenic phenylalkylamines is a phenethylamine
group, which is a prevalent structure in a range of endogenous compounds, including
the neurotransmitters dopamine and norepinephrine.179 Indolamines contain an indole
nucleus as basic structure, having a high structural similarity with 5-hydroxytryptamine
(5-HT or serotonin), a monoamine neurotransmitter that modulates human mood and
behaviour. 179,180
Indolamines can be subclassified into two main groups:
i. The simple tryptamines (including substances like DMT and psilocybin) that can be
subdivided according to the site of the modification.
ii. The ergolines such as LSD.179
Following absorption, tryptamine analogues undergo phase I and phase II metabolism.
The ergoline LSD is extensively metabolized and <1% of the ingested dose is
eliminated unchanged in urine. The analysis of urine from LSD users identified five
metabolites, namely the 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, N-desmethyl-LSD, 13- and
14-hydroxy-LSD glucuronides.181 Psilocybin (a 4-substituted indolamine) is rapidly
dephosphorylated by phosphatases in the digestive tract, in kidney and probably in the
humanblood to generate its pharmacologically active metabolite psilocin. Oxidative
deamination of psilocin to form 4-hydroxyindole acetic acid (4-OH-IAA) constitutes a
minor metabolic pathway.182 Psilocin is further metabolized by phase II enzymes to give
the psilocin-O-glucuronide, which is the main metabolite detected in human urine. 182
Like 5-HT itself, some tryptamine derivatives including DMT, 5-OH-DMT and 5-MeO-

DMT are extensively metabolized through oxidative deamination to their

corresponding indole acetic acid (IAA) derivatives mediated by monoamine oxidase A
(MAO-A).183
2.6.2. Neurobiology
There is high correlation between the affinity to 5-HT2 receptors and hallucinogenic
potency in humans.184 Radio-ligand binding studies showed that phenylalkylamine
hallucinogens such as mescaline are typically selective for 5-HT2 receptors, including
the 5-HT2A, 5-HT2B and 5-HT2C subtypes.184 Like phenylalkylamines, the
tryptamine hallucinogens such as LSD, psilocin, DMT or 5-MeODMT act as 5-HT2
receptor agonists, but they are much less selective, binding to a variety of 5-HT1 and 5-
HT2 receptor subtypes (including 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2A and 5-HT2C
receptors) with different affinities.179,185 Tryptamine derivatives, in general, exert their
effects by binding to and activating primarily the serotonin 5-HT2A receptor, which is
mainly responsible for the effects of hallucinogens.179 DMT is described as sigma-1 (σ 1)
receptor agonist with moderate affinity, although this is not its main interaction, since
DMT affinity for 5-HT1A and 5-HT2A receptors is twice greater than for σ 1.186
Dopaminergic and adrenergic receptors play an additional role in mediating certain
aspects of the behavioural effects provoked by these compounds.186 Ibogaine interacts
strongly the NMDA receptor, σ –receptors, µ -opioid receptors, and muscarinic
receptors.187 It also causes serotonin and dopamine reuptake inhibition at their
transporters (SERT and DAT).188
Users experience euphoria, mild stimulation, enhanced appreciation of music and
lights, visually appealing distortions, intensification of sensual or sexual feelings,
altered sense of time and place, and a sense of shared and heightened significance of the
situation with the intake of hallucinogens. The effects of the hallucinogens are dose
dependent. One hallucinogen i.e. 2C-B has been described as inducing 'perceptual
enhancement' and euphoria (hence more used in raves/clubs and popular as a dance
drug), but these are milder than those of classical hallucinogens such as LSD and the
drug lacks the potent hallucinogenic effects of LSD.
Unwanted psychological effects of hallucinogens are referred to as a 'bad trip', and are
characterised by anxiety, fear/ panic, dysphoria and/or paranoia. Distressing effects can
be sensory (e.g. frightening perceptions), somatic (e.g. distressing awareness of
physiological processes), personal (e.g. troubling thoughts or feelings) or even
metaphysical (e.g. feelings about evil forces). In very rare cases, fear and paranoid
delusions may lead to erratic behaviour and potential aggression against self and
others.189 Even when a user is not experiencing a 'bad trip', unwanted effects can include
confusion, disorientation, anxiety and unwanted thoughts, emotions and memories.

Club Drugs
Symptoms of hallucinogen overdose involve almost all the organ systems of the body
which is shown in Table 5.
Table 5: Symptoms of overdose and toxicity of LSD and related hallucinogens
Organ system Symptoms

Central nervous Dilated pupils, mydriasis, (common with psilocybin), sensory
system distortions, visual & auditory illusions, synaesthesia &tactile
hallucinations, e.g. formication, affect lability, euphoria
dysphoria, acute panic, paranoia, ideas of reference,
depersonalisation, anxiety disorientation dissociation
agitation, aggression, combativeness delirium depression,
suicidal ideation, attempted suicide, psychosis, delusions,
hallucinations seizures confusion ataxia 'bizarre behaviour'
lightheadedness, headaches, paraesthesias, abnormal
sensations of heat and cold, chills, restlessness and excitement
Cardiovascular Tachycardia and hypertension
system
Musculoskeletal Myalgia, twitching, shaking,muscle tension and
system jaw clenching
Respiratory system Tachypnoea
Metabolic Metabolic acidosis
Gastrointestinal Nausea, vomiting (psilocybin commonly) and diarrhoea
system
Renal Acute kidney injury/acute kidney failure, rhabdomyolysis
Others Hyperthermia, pyrexia, hypoglycaemia, flushing and sweating
A study using data from the large representative sample of the US National Survey on
Drug Use and Health found that the use of hallucinogenic drugs appears not to be
causally linked to the de novo development of chronic disorders of mental health such
as schizophrenia or depression.190 Hallucinogens are rarely a cause of substance-
induced psychosis, where the drug triggers a psychotic episode that may persist hours,
days or even weeks after the acute intoxication should have run its course.191
Nonetheless, psychotic symptoms in the context of LSD use have been reported. Salvia
can trigger psychosis in people with existing psychotic illnesses or predispositions.
Psilocybin mushrooms can cause an exacerbation of psychosis. A greater psychotic
response to LSD in persons with a genetic predisposition to schizophrenia has been
observed.192

Hallucinogen persisting perception disorder (HPPD) and 'flashbacks' have been

associated with use of classic hallucinogens in particular, although these concepts
remain uncertain. HPPD as a diagnosis has been embraced by a group of people
experiencing longer-term symptoms resulting from hallucinogen use. HPPD can persist
for months or years after the use of hallucinogens. For some, this long-term change to
vision and hearing is much less problematic than for others, for whom it can cause
substantial morbidity.193,194
The diagnostic criteria of HPPD as defined by DSM-5 (292.89) are as follows:
A. Following cessation of use of a hallucinogen, the re-experiencing of one or more of
the perceptual symptoms that were experienced while intoxicated with the
hallucinogen (e.g. geometric hallucinations, false perceptions of movement in the
peripheral visual fields, flashes of colours, intensified colours, trails of images of moving
objects, positive afterimages, halos around objects, macropsia, and micropsia).
B. The symptoms in Criterion A cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
C The symptoms are not due to a general medical condition (e.g. anatomical lesions
and infections of the brain, visual epilepsies) and are not better accounted for by another
mental disorder (e.g. delirium, dementia, schizophrenia) or hypnopompic
hallucinations.
In contrast, ICD-10 views this disorder within the wider paradigm of a psychotic
disorder (F1x.5) and specifically considers 'flashbacks' (F1x.70) within the context of
'residual and late-onset psychotic disorder' (F1x.7). ICD-10 also specifies that
'flashbacks' 'may be distinguished from psychotic disorders partly by their episodic
nature, frequently of very short duration (seconds or minutes) and by their duplication
(sometimes exact) of previous drug-related experiences'.
LSD has been involved in a small number of fatalities attributed to 'excited delirium',
more commonly associated with cocaine. Excited delirium has also been associated
with 5-MeO-DALT and alpha-MT. It has been argued that, in some instances, fatalities
attributed to excited delirium may reflect underlying serotonergic and/or
sympathomimetic toxicity.24
2.6.4. Management
2.6.4.1. Management of hallucinogen toxicity
The management of acute toxicity resulting from the use of hallucinogens will in part
depend on the hallucinogenic substance consumed. It has been suggested that
monitoring and supportive treatment is all that is required for the majority of patients
including airway management.195

Club Drugs
Attempts to 'talk the patient down' first must be instituted. Sympathetic, non-
judgemental reassurance, support and observation are often sufficient. Where possible,
the patient should be placed in a well lit room with minimal disturbance. Patients may
be prone to mistrust and paranoid ideation and early efforts in empathising, expressing
understanding of their fears and establishing confidence have been shown to be
beneficial.189
Benzodiazepines, particularly diazepam or lorazepam195,196 have been reported by some
studies to be first-line choice if pharmacological interventions are needed and in cases
of agitation (IV).189 In most of the case 10 mg oral doses of diazepam (0.1–0.3 mg/kg
body weight) is sufficient (IV).24 Doses of 15–30 mg per hour or as needed have been
suggested for cases of 'bad trips' that do not respond to reassurance in an emergency
department setting.189 Larger doses may be required. Antipsychotics should be
considered as a second line if benzodiazepines do not produce adequate sedation (IV).24
In cases of severe agitation or 'excited delirium', physical restrain should be avoided, as
this is associated with sudden cardiovascular collapse.197
Recommendations
l Patient should be placed in a quiet, well lit room with minimal external stimuli (S)
l Benzodiazepines, diazepam or lorazepam are the mainstay of treatment,
particularly in presence of agitation (D)
l Antipsychotics can be considered as second line treatment (D)
2.6.4.2. Management of hallucinogen dependence
The use of LSD or other classic hallucinogens does not appear to lead to dependence.
Typically there is no persistent and compulsive pattern of use and the use of
hallucinogens is not associated with any recognised withdrawal syndrome.198
Hallucinogens do not appear to show classic patterns of tolerance, but, on the contrary,
are associated with tachyphylaxis.179 This means that sensitivity to the effects of LSD and
other hallucinogens appears to be strongly attenuated for a period after use. It may
therefore prove difficult for a user to achieve desired effects from LSD if taken two days
in a row, or indeed to get a desired effect from other hallucinogens.168,179
2.6.4.3. Management of HPPD
Pharmacological interventions for HPPD have been used but many of the studies
(especially older ones) had methodological limitations. These interventions have
included several classes of antidepressants, anxiolytics and antipsychotics, a COMT
inhibitor, naltrexone, levodopa, clonidine, lamotrigine and citalopram (IIb).24 Over the
years, there have been reports of treatment using haloperidol, diphenylhydantoin,
trifluoperazine, barbiturates, benzodiazepines, carbamazepine, sertraline, naltrexone,
clonidine, and a combination of olanzapine and fluoxetine(IIb).24 Hermle et al. have

suggested that the anti-epileptic lamotrigine may be a promising new medication for
HPPD (IV).24,199
Recommendations
Several classes of antidepressants, anxiolytics,
l antipsychotics, COMT inhibitor,
naltrexone, levodopa, clonidine, lamotrigine and citalopram can be used to treat
HPPD (B)
Lamotrigine may be a promising agent in the treatment of HPPD (D)
l
3. GENERAL PRINCIPLES IN THE MANAGEMENT OF CLUB DRUG

INTOXICATION / HARMFUL USE / DEPENDENCE
Because club drugs are illicitly obtained and often are adulterated or substituted, they
are usually known as unknown substances. In the ever-changing world of illegal drug
distribution, Internet Web sites can be helpful in identifying the rapidly changing
appearances of these substances.23 Urine and serum toxicology screens may not be able
to detect club drugs. For example, urine screening does not detect MDMA, though it
does detect its metabolite, MDA. Ravers often present with concurrent ingestion of
drugs with different pharmacological profile, which may include stimulant and
depressant drugs. Therapist should always make an attempt to gather information from
as many sources as possible regarding what was ingested and in what form.
Table 6 : Treatment strategies for Club Drugs (adapted from Gahlinger, 2004)23
What drug was taken?
Not sure Positive identification of drug
Ask for sample, description, Consider adulteration,

or visual identification or drug substitution
Cardiac monitoring
Pulse oximetry
Urinalysis
Chemistry panel
Toxicology screen if available
Seizure precautions
Consider escape and self-injury

Club Drugs
If less than 60 minutes since

ingestion, consider gastric lavage
Stimulants: Depressants:
MDMA Flunitrazepam
Ketamine (Ketalar) GHB
Anxiety or agitation: Benzodiazepines

e.g. Diazepam/Lorazepam/Midazolam
Severe hypertension: Labetalol/
Phentolamine/Nitroprusside
Hyperthermia: rapid cooling\
Serotonin syndrome: Cyproheptadine/
Chlorpromazine
Rhabdomyolysis: alkaline IV fluids (5% D
with Sodium Bicarbonate)
Provide supportive care.

Consider flight risk.
Consider psychiatric consultation
Provide education to patient and
No standard treatment protocol has been identified for club drug overdose. Basic
management should include cardiac monitoring, pulse oximetry, urinalysis, and
performance of a comprehensive chemistry panel to check for electrolyte imbalance,
renal toxicity, and possible underlying disorders (Table 6).23 Every effort should be made
to control seizures. Gastrointestinal decontamination with activated charcoal and a
cathartic may be useful in acute exposures if the drug was taken orally within the
previous 60 minutes. Severe hypertension can be treated with labetalol, phentolamine,
nitroprusside, or similar agents. Hyperthermia should be treated immediately with tepid
water bathing and fanning. The serotonin antagonists chlorpromazine and
cyproheptadine appear to be effective in mild to moderate cases of serotonin
syndrome.200 There are no specific antidotes for ingestion of club drugs, except for
Flunitrazepam, which has already been mentioned.165 In view of the above, an
alternative is to encourage harm reduction strategies (Table 7)2 by ensuring that
buildings meet safety and health standards, adequate security is provided to

accommodate the large number of attendees and ravers are educated about health
effects by trained volunteers. NIDA website (www.clubdrugs.org) also provides useful
information regarding club drugs.
Table 7: Harm reduction strategies for raves (adapted from Weir, 2000)2
l Replenish fluids and sodium (500 mL/h if dancing, 250 mL/h if inactive)
l Take breaks from dancing
l Know the risks of adulterated drugs and the inaccuracies of logos
l Know the signs and symptoms of toxicity
l Avoid alcohol
l Ensure medical centre and team is on-site
l Don't attend a rave alone; contract with a friend to look out for each other
As with other psychoactive substances, various psychosocial interventions can be
planned for the management of club drugs dependence. These include motivational
interviewing, contingency management, CBT based relapse prevention, community
reinforcement approach, behavioural therapies, social behaviour network therapy,
supportive expressive psychotherapy so on and so forth (IV).201,202 However, in the
absence of any controlled clinical trial of psychosocial interventions for the
management of club drugs dependence, specific recommendation cannot be made.
UNODC's Global Synthetics Monitoring: Analyses, Reporting and Trends (SMART)
Programme aims to provide quality information on ATS, such as patterns of trafficking
and use, and will provide the international community with the evidence needed to
take more targeted action in areas of weakness.203 An illicit club drug community
intervention programme, 'Clubs against Drugs', was initiated in 2002 in Stockholm,
Sweden. The illicit club drug intervention was based on a systems approach top
revention.204,205 The programme included community mobilization, drug training,
increased enforcement,policy work, environmental changes and media advocacy and
public relation (PR) work [18,21] In a pre- (2003) and post-intervention study (2004 & 2008)
design The 'Clubs against Drugs' community-based intervention programme, appeared
to increase the frequency and effectiveness of club doormen's interventions regarding
obviously drug-intoxicated guests (III).206
4.1. RECOMMENDATIONS
l Suspicion of a club drug overdose /toxicity is essential
l Except for GHB, club drugs cannot be detected through routine toxicological
screens, so one should not waste valuable time
l Maintainairway, breathing and circulation (S)

Club Drugs
l Gastrointestinal decontamination with activated charcoal is recommended if

ingestion has happened within last 1 hour (S)
l Hyperthermia and Serotonin syndrome should be managed with tepid sponging and
cyproheptadine/chlorpromazine respectively (S)
l Flumazenil may be administered to reverse the effects of flunitrazepam toxicity
(D, S)
l Psychosocial interventions in various forms can be effective for the management of
club drugs dependence (D)
l Long term community intervention programs e.g. 'Club against Drugs' has shown
some promise (C)
4. CLUB DRUGS: INDIAN SCENARIO
Indian data related to club drugs are very limited with little efforts being made to gather
systematic data regarding the same. The first nationwide survey to obtain information
on extent, pattern and magnitude of substance abuse in the country indicated new
emerging trend of substance use in India with amphetamine like substances (ATS) are
being more used in regions like Goa and Ahmedabad.207 Most reports regarding club
drugs are from newspaper articles; hence there is an urgent need for verified, authentic
research data.
A recent assessment by United Nations Office on Drugs and Crime (UNODC)203 has
found that after substantial increases in the late 1990s, the use of synthetic drugs (e.g.,
amphetamines and Ecstasy) in North America, Europe and Oceania has stabilized,
albeit at high levels. But the problem has shifted to new markets, particularly in East and
South-East Asia and the Middle East over the past few years. With technological
advancement and particularly the information technology sector coming up in a big
way in India (often as outsourcing for overseas-based multinational companies),
suddenly there is a neo-rich young generation. This is often coupled with the need to
escape temporarily from the severe work pressure and social isolation created by this
lifestyle. With drug licensing and controlling authorities focusing more on licit and
traditional illicit drugs (e.g. opioid, cannabis), club drugs have caught the fancy of this
neo-rich young generation. Table 8 lists the various factors/reasons behind the
significance of this new and emerging phenomenon in the Indian drugs scenario and
why we should be concerned.
Table 8 : Why India should be concerned about Club Drugs?
1. These are often associated with status symbol amongst the neo-rich youth
2. These are often perceived to be safe or benign compared to the “hard drugs” such
as heroin, cocaine etc.

3. Some of these drugs (e.g., GHB, Rohypnol) are notorious as “rape drugs” and their
use is associated with crimes like date-rape, party rape, robbery, etc.
4. Unlike cannabis, opium or heroin, these are usually imported or smuggled from
neighboring countries
5. Some of these (e.g., MDMA) are directly neurotoxic in short and long term use
6. Contrary to their popular perception, all these drugs can have substantial toxic
effects on several systems of the body and can be potentially lethal (see Table 1,
'Toxic effects', for details)
7. These are difficult to detect through routine toxicological screening (GHB is an
exception);
8. These are notorious for spreading sexually transmitted diseases (STDs) and HIV
infection because of their intravenous route of administration
9. These are devoid of any antidote (flunitrazepam is an exception)
10. Management needs to be started early and can be difficult (see Table 6 for details)
Adapted from Chakraborty K, Neogi R, Basu D. Club drugs: Review of the 'rave' with a
note of concern for the Indian scenario. Indian J Med Res 2011;133:594-604.25
The rave parties of Goa are said to be started by the Hippies.208 Earlier Rave parties meant
loud music, alcohol and cannabis abuse. Since the late eighties, psychedelic culture in
the northern village of Anjuna became increasingly concentrated on free out-door
parties with a particular subgenre of electronic dance music, which by 1994 was known
as Goa trance and later became much darker, more minimal and aggressive, called psy-
trance.208 Rave parties in Goa happen every tourist season (November to May) which are
attended mainly by foreigners from the UK, Israel, Germany, France and Japan.209 The
bars organizing such parties sell Ecstasy or LSD.210 In last few years upper-class Indians
have massively taken to Ecstasy and clubbing and there are more women amongst
them.208 The CK1 pill is one of the trendy party drugs manufactured locally in Goa. The
pill is a combination of cocaine and the anaesthetic ketamine. CK1, also known by its
street names Blizzard and Calvin Klein, is easily available in the north Goa beach belt.
Customs officials admit that the clandestine production and smuggling of ketamine is
turning Goa into a transit point for an international drug mafia.211
Thanks to its booming software industry, Bangalore is baptized the Silicon Valley of
India and has turned into a rave hotspot.212 The spot lights in the clubs create an
atmosphere between cosy and disco, everybody drinks, most smoke and a few take
psychedelic drugs.212,213
In Pune, 280 people were arrested during a pre-dawn raid on a rave party in March
2007. The ravers were allegedly using California drops.214 A California drop is acid that

Club Drugs
is put on a stamp, which is then chewed; the cost of each drop is put between INR 350
and 500.
Also known as white magic, drone, and mephedrone, “meow meow” is the latest and
cheapest street drug hitting Mumbai which was not even in the list of government-
banned drugs until February 2015.215 A very recent newspaper article reported that African
connection to drug peddling in the city of Hyderabad seems to be on the wane. Records
from the Narcotics Control Bureau revealed that drug rackets have moved closer home,
with suppliers now mostly hailing from Nepal and Myanmar.216
Sometimes police directly raid rave parties in plain clothes and catch ravers red-handed.
People who are found in the Rave Party are often booked under Section 27 of the
Narcotic Drugs and Psychotropics Substances Act of 1985 and Section 294 of the Indian
Penal Code.
5. CONCLUSION
Club drugs are a menace to the society. Their use, other than for strictly medical or
approved research purposes, should be prohibited through legislation and awareness
generation. Even though the “club drug” phenomenon was identified early, scientific
information about these drugs, their identification, and short- and long-term effects are
still evolving. The lack of research-based information on the adverse effects of these
drugs has led to the emergence of a range of web sites that may or may not provide
accurate information. India has a huge teenage population which is being targeted by
foreign drug peddlers to flourish their business. Club drugs continue to be modified and
evolve, making them very difficult to monitor. As health professionals we should remain
well informed regarding club drugs and their management protocol. To the best of our
knowledge this is the only guideline which solely focuses on the management of club
drugs toxicity, dependence and withdrawal and makes specific recommendations to
manage those conditions. There is another guideline24 which deals with the
management of acute and chronic harms of club drugs along with other psychoactive
substances. Therefore, this guideline provides us with a unique opportunity to make
ourselves familiar with various club drugs available in the market and enable us to deal
more effectively with the medical problems arising out of using these substances.
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SECTION C :
BEHAVIOURAL ADDICTIONS
GAMBLING DISORDER
Abhishek Ghosh
Debasish Basu
P.K. Dalal
On behalf of
2016
Gambling Disorder
CONTENTS
Executive Summary
1. Introduction
3. Assessment of gambling disorder/ pathological gambling (GD/PG)
3.1 Diagnosis of GD
3.1.1 Screening questionnaire
3.1.2 Structured interviews
3.2 Exploration for co-morbidity
3.3 Exploration for psycho-social consequences
4. Treatment setting
5. Treatment for gambling disorder (GD)/ pathological gambling (PG)
5.1 Pharmacological management for gambling disorder (GD)
5.1.1 Opioid antagonists
5.1.2. Antidepressants
5.1.3. Mood stabilizers
5.1.4. Other group of medications
5.2 Psychosocial treatment for gambling disorder (GD)
5.2.1 Gamblers Anonymous
5.2.2. Self help measures
5.2.3. Cognitive behaviour therapy
5.2.4. Brief intervention and motivational intervention
5.2.5. Family therapy
5.2.6. Combined psycho-social approach
5.3 Combined psychotherapy and drug treatment
6. Caveats in the proposed guideline

Gambling Disorder
EXECUTIVE SUMMARY
Introduction- Gambling, as a ubiquitous method of entertainment is present since
antiquity. However, gambling is mostly recreational, only in a minority it causes
significant socio-occupational dysfunction, and in a further smaller fraction of
individuals it becomes an uncontrollable pre-occupation that persists despite significant
negative consequences, resulting in a disorder. Gambling disorder (GD) was
introduced in the Psychiatric nosology in 1980's in the 3rd Edition of DSM [and also in
ICD-9] as pathological gambling. In DSM-5, it is included in the section of substance use
and related addictive disorders as Gambling Disorder. It is reasonably common in
clinical setting. Gambling disorder leads to devastating psychosocial consequences and
is associated with poor quality of life. Cumulative evidence for the treatment of
gambling disorder, which ranges from psychosocial to pharmacological, has
demonstrated significant efficacy in reducing the severity and consequences of
gambling.
Assessment for GD- Assessment and diagnosis of GD is entirely clinical and hence
based upon a detailed history and mental status examination. History from the
individual must be corroborated from the family members where ever possible. A
comprehensive assessment of GD must consist of the following:
Screening and establishing confirmed diagnosis
l
Exploration for co-morbidity
l
Exploration for psychosocial consequences
l
Screening and diagnostic instruments are reviewed in the guideline. The frequency and
pattern of co-morbidity have been discussed. The adverse psycho-social consequences,
the exploration of which are deemed necessary an additional have been mentioned.
Treatment setting- Although no systematic assessment has been conducted so far, the
usual locus for the treatment of GD is the out-patient clinics. Inpatient treatment is most
likely to take place if the individual is hospitalized for another psychiatric disorder,
including substance use disorders.
Pharmacological treatment for GD - Various treatment options have been investigated
for pharmacotherapy of gambling disorder, namely the opioid antagonist,
antidepressants, mood stabilizers, and glutamatergic agents. Naltrexone could be
considered as the first line pharmacological treatment for gambling disorder (GD).
Dosage required could be more than the usual dose used for the treatment of alcohol
dependence. [A] N-acetyl-cysteine (NAC) could be another promising first line agent
following naltrexone [A]. Second line agents: fluvoxamine (~200 mg/day) [B],
paroxetine (~50 mg/day) [B], memantine (~20mg/day), tocapone, and acamprosate
[C]. Although treatment of GD in presence of co-morbidity has not been investigated

systematically, evidence suggests that escitalopram and lithium could be used for
concurrent anxiety disorder and bipolar disorder respectively.
Psychosocial treatment for GD - Research in the area of psychological treatment for GD
is probably better developed as opposed to the pharmacological treatment. Several
treatment options for gamblers have been explored, ranging from self-help and peer
support, to brief and motivational interventions, to more intensive therapy approaches.
In depth motivational intervention (MI) or short term (~4 sessions) motivation
enhancement therapy could be first line treatment options as a sole form of treatment [A]
or brief motivational intervention could be used in conjunction with other forms of
intensive interventions (especially CBT) to improve treatment retention [A].More
intensive intervention especially CBT could be considered for long term engagement
[A].CBT could be delivered in both individual and group format [A]. Components of
CBT includes: cognitive restructuring, relapse prevention [A], skill training, behavioural
interventions (like cue conditioning/extinction) [B]. Bibliotherapy (proving workbooks)
could be used along with either MI or CBT [A]. Second line therapy options could be:
twelve step facilitation (TSF) [A], Exposure based therapy [B], and family therapy [C]. The
overall empirical evidence for the efficacy of psychological intervention in terms of both
quantity and quality of studies is better than pharmacological treatment. Hence, it must
be offered to all patients seeking treatment for GD.
The document ends with important caveats that should be borne in mind while
interpreting and following the guideline. .

Gambling Disorder
1. INTRODUCTION
Gambling, as a ubiquitous method of entertainment is present since antiquity. In
gambling, the individual places something of value at stake in the hope of getting
something of greater value. Perhaps, it originated in Korea, and spread across the
Europe, USA, and Asia. In the ancient and medieval India, it was present as dice games;
in the pre-independence and colonial era horse racing was a highly cherished activity
amongst the relatively affluent Indian communities.1 In the 90's lotteries was the
legalized form of 'gambling'. Presently perhaps cricket betting has become the 'state of
the art' gambling! However, most of the gambling are recreational, only minority causes
significant socio-occupational dysfunction and in further smaller fraction of individual it
becomes a pre-occupation and uncontrollable and persists despite significant negative
consequences, resulting into disorder.2 Gambling disorder (GD) was introduced in the
Psychiatric nosology in 1980's in the 3rd Edition of DSM [and also in ICD-9] as
pathological gambling (PG) along with other impulse control disorders like
kleptomania, pyromania, and trichotillomania.3-5 However, the diagnostic criteria laid
down for pathological gambling were based on criteria for substance dependence.
Because there is no substance involved in gambling, it could not be incorporated under
the section of substance use disorders, despite its clinical-phenomenological,
biological, and even treatment related similarities with the latter.6 This limitation has
been subverted in DSM-5 which has brought about a significant change in the section of
substance use disorders by incorporating addictive disorders (includes behavioural
addictions).7 Henceforth, pathological gambling which was 'out of place' for more than
three decades after its inception could be included in this section as gambling disorder.
The elimination of the pre-fix pathological is to reduce stigma associated with the word
and perhaps to establish a phonemic similarity with other substance use disorders (for
e.g. alcohol related disorders).6 This recent change in the nosology is likely to improve
recognition of the disorder, especially among substance users who are at high-risk for
GD.8 However, in ICD-10 it is still specified as Pathological Gambling (PG). Hence,
both these terms have been used interchangeably in the current document.
Prevalence of PG varies widely depending upon the locus and modus of the study. The
first three national level survey conducted in the US were telephone based and the
prevalence ranged from 0.8-2% .9-11 The first in-person national level study done as a part
of National Epidemiological Survey of Alcohol and Related Conditions (NESARC)
revealed a prevalence figure of 0.4% in general population.12 A large body or research
also exists across the continents 13and across a diverse population (college students,
adults, children, and specific ethno-cultural group. The figures of PG hover around 0-
4% and 1.7-8.5% amongst adults and child/adolescent respectively.13 Prevalence of PG
is significantly more in substance using population. A meta-analysis of 18 studies
amongst the treatment seeking substance users, the lifetime rate of PG was 14%.14 Other

large scale individual studies focusing on the substance users observed a prevalence
figure ranging from 10-13%.15 One Indian study which assessed problem gambling(not
PG/GD) in treatment seeking substance using population observed a prevalence of
7.4% in the past year.1
Gambling disorder leads to serious psycho-social consequences. It is associated with
poor quality of life, high rates of bankruptcy, divorce, and incarceration. Gambling
losses might lead to psychiatric hospitalizations because of secondary depression and
suicidality.16 The overwhelming financial consequences and guilt associated with GD
places the individual at higher risk of suicidal attempts. A study among Gamblers
Anonymous (GA) participants has revealed suicidal attempt as high as 25% .17 Despite
all these negative consequences the rate of treatment seeking is a very low in GD. The
likely cause ranges from external barriers for seeking help to personal factors.18 People
who seek treatment mostly do so for their substance use or psychiatric problems and
seldom for gambling per se.
Although a couple of decades ago treatment literature regarding GD revolved around
case reports, case series and controlled trials with serious methodological limitations,19
over the last decade there has been several methodologically validated research in this
area. Cumulative evidence for the treatment of gambling disorder, which ranges from
psycho-social to pharmacological, has demonstrated significant efficacy in reducing the
severity and consequences of gambling. To the best of our knowledge, till now there is
no published clinical practice guideline (CPG) dedicated in this important area. The
objective of the current guideline is to study the available evidence, determine its
strength and finally to recommend practical treatment options especially suited to the
Indian context.
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) to identify published
meta-analysis, reviews, open-label trials, randomized double-blind trials, placebo-
controlled trials, and case reports written in English, focusing on the pharmacotherapy
of pathological gambling. In addition, we have searched Scopus, Google Scholar, and
PsychInfo to identify any other study missed. The following keywords were used:
gambling disorder, pathological gambling, problem gambling, pharmacotherapy,
psychological therapy and treatment. The search was conducted on 4th June, 2015.
Only selection of clinical trial had yielded 203 results; inclusion of reviews had
increased the number of results to 509.
We have used the term gambling disorder (GD) and pathological gambling (PG)
interchangeably throughout the document.

Gambling Disorder
2. ASSESSMENT OF GAMBLING DISORDER/ PATHOLOGICAL GAMBLING

(GD/PG)
Assessment and diagnosis of GD is entirely clinical and hence based upon a detailed
history and mental status examination. History from the individual must be
corroborated from the family members where ever possible. A comprehensive
assessment of GD must consist of the following:
l Screening and establishing confirmed diagnosis
l Exploration for co-morbidity
l Exploration for psycho-social consequences
3.1 Diagnosis of GD
The diagnosis of GD is primarily based on exploring and establishing the diagnostic
criteria laid down for this disorder in the current nosology. [Panels 1, 2 and 3]
Panel 1
ICD-10 criteria for PG
l Individuals have frequent and repeated episodes of gambling despite adverse
consequences
l Individuals put their jobs at risk, acquire large debts, and lie or break the law
l Individuals have intense urges to gamble, which are difficult to control
l Individuals have preoccupation with ideas and images of the act of gambling
l Should be distinguished from gambling and betting (frequent gambling for
excitement or in an attempt to make money), excessive gambling by manic
patients, and gambling by sociopathic personalities
Panel-2
DSM-IV TR criteria for PG
Persistent and recurrent maladaptive gambling behaviour is indicated if the
individual has five (or more) of the following:
l Is preoccupied with gambling
l Needs to gamble with increasing amounts of money
l Has repeated unsuccessful efforts to control, cut back, or stop gambling
l Is restless or irritable when attempting to cut down or stop gambling
l Gambles as a way of escaping from problems or of relieving a dysphoric mood
l After losing money gambling, often returns another day to get even (i.e.,
“chasing one's losses”)

l Lies to conceal the extent of involvement with gambling

l Has committed illegal acts to finance gambling
l Has jeopardised or lost an important relationship, job, or educational or career
opportunity because of gambling
l Relies on others to provide money to relieve a desperate financial situation
caused by gambling
The gambling behaviour is not better accounted for by a manic episode
Panel-3
DSM-5 criteria for GD
Persistent and recurrent problematic gambling behaviour leading to clinically
significant impairment or distress, as indicated by the individual exhibiting four (or
more) of the following in a 12-month period:
l Needs to gamble with increasing amounts of money in order to achieve the
desired excitement.
l Is restless or irritable when attempting to cut down or stop gambling.
l Has made repeated unsuccessful efforts to control, cut back, or stop gambling.
l Is often preoccupied with gambling (e.g., having persistent thoughts of reliving
past gambling experiences, handicapping or planning the next venture, thinking
of ways to get money with which to gamble).
l Often gambles when feeling distressed (e.g., helpless, guilty, anxious,
depressed).
l After losing money gambling, often returns another day to get even (“chasing”
one's losses).
l Lies to conceal the extent of involvement with gambling.
l Has jeopardized or lost a significant relationship, job, or educational or career
opportunity because of gambling.
l Relies on others to provide money to relieve desperate financial situations
caused by gambling
The gambling behaviour is not better accounted for by a manic episode
Current severity:
Mild: 4–5 criteria met.
Moderate: 6–7 criteria met.
Severe: 8–9 criteria met.
NOTE: “Has committed illegal acts to finance gambling” has been removed from
the diagnostic criteria

Gambling Disorder
3.1.1 Screening questionnaire

There are several screening instruments developed for PG, which can be applied both
for clinical and for general population. For a detailed review the readers are suggested to
go through the chapter written by Stinchfield et al. (2007).20 The purpose of a brief
screen is to identify individuals who may have a gambling disorder; it helps to narrow
down the number of people who will be referred for more time-intensive and costly
comprehensive assessment. The mean time required for administering a screening
instrument ranges from 1-5 minutes.
Amongst them South Oaks Gambling Screen (SOGS) which is based on DSM-III criteria
for PG and has 20 questions is perhaps the most widely used screening questionnaires.21
This instrument has been translated into several languages without affecting its
reliability and can be administered both in the interview or self-report format. It has
three versions for the lifetime, past year, and past 3 months diagnosis of PG. The
sensitivity (0.99) of the instrument overshadows its specificity (0.75), which has made it
as one of the reliable screening instruments.22 A relatively brief screening instrument
Problem gambling Severity Index (PGSI) which has 9 items is based on DSM-IV criteria
of PG. The use of this instrument is gradually increasing in recent times. It has both high
sensitivity (0.83) and an excellent specificity (1.0) for the diagnosis of problem gambling
(score>8 is indicative of PG).23 A third screening instrument for gambling is known as
Massachusetts Gambling Screen (MAGS). This test looks for signs and symptoms of PG
and psychological and social problems associated with gambling disorders as in DSM-
IV. It is a 14-item questionnaire and seven items are scored with a past year time frame.
MAGS items are scored by multiplying each item times a discriminant function
coefficient, and then added together with a constant. A score between 0 and 2 labels a
“transitional gambler” or PPG. A score greater than 2 indicates PG.24 Another instrument
is the 17-item National Opinion Research Center DSM-IV Screen for Gambling
Problems (NODS), which was originally developed for a US national gambling
telephone survey and was based on past-year and lifetime DSM-IV diagnostic criteria for
pathological gambling.25 The diagnosis of PG is based on a cut-off score, the validity of
which is yet to be established systematically.26 A 3-item short version of NODS, known
as NODS-CLiP observed to have excellent sensitivity (0.94) and specificity (0.96), when
tested in the community sample. This screening instrument explores three areas, loss of
control, lying and preoccupation and positive response in any one of the items calls for a
detailed evaluation.25 Brief Biosocial Gambling Screen (BBGS) a recently developed
screening instrument which also has 3 questions assesses PG over last one year as
opposed to the NODS-CLiP which is for the lifetime diagnosis of PG. An alternative
four-item screen that demonstrates improved sensitivity, good positive and negative
predictive power and invariance across key demographic groups had been developed.
As it is derived from NODS, It is known as Preoccupation, Escape, Risked Relationships

and Chasing (PERC).27 Given high rates of comorbidity, routine and accurate
identification of gambling-related problems among individuals seeking help for
substance abuse and related disorders is important. BBGS was derived from the
NESARC study and was based on DSM-IV PG.28 It also has similar high sensitivity and
specificity like the NODS-CLiP. However, the validity of these 2 instruments has not
been established yet from different sample and for clinical population. A recent study
has compared the brief screening instruments with the DSM-5 criteria for GD. Both
NODS-CLiP and NODS-PERC had been found to have excellent accuracy at all cut-off
points. However, BBGS had the best accuracy.29 The shortest possible screening tool for
PG is the Lie/Bet scale. Its Items determine if individual lies to others about gambling
behaviours or bets more and more money. There are 2 items with “yes/no” response
options in a lifetime time frame. Answering “yes” to one or both items indicates PG.30
3.1.2 Structured interviews
For a more comprehensive assessment, the Gambling Treatment Outcome Monitoring
System (GAMTOMS) is a multidimensional self-report or interview assessment
instrument. GAMTOMS incorporates SOGS and also assesses various domains
pertaining to treatment planning and outcome monitoring, including gambling
frequency, mental health, financial problems, legal problems, and motivation.
Additionally, this system has a ten-item DSM-IV measure that is relevant for diagnostic
purposes. GAMTOMS has been used for several psychometric evaluations in clinical
samples, whereby DSM-IV categorical diagnosis of pathological gambling had good
sensitivity (0·96) and specificity (0·95) for distinguishing clinician-diagnosed cases from
non-cases, as well asgood sensitivity (0·96) and specificity (1·0) distinguishing SOGS-
positive cases from SOGS-negative cases. GAMTOMS also includes a follow-up version
that measures treatment outcome via self-report.31Another comprehensive instrument
for the diagnosis of GD is Diagnostic Interview for Gambling Schedule (DIGS). This
instrument measures demographics, gambling involvement, treatment history, onset of
gambling, gambling frequency, amounts of money bet and lost, sources of borrowed
money, financial problems, legal problems, mental health screen, other impulse
disorders, medical status, family and social functioning and diagnostic symptoms
(lifetime and past year). It has total 20 items and is based on DSM-IV TR diagnostic
criteria. If respondent endorses either of the two items per criterion, the criterion is
considered endorsed.32 The details of all instruments have been summarized in Table 1.
However, an interview by a qualified psychiatrist is always the gold standard for the
diagnosis of GD. Other diagnostic/screening instruments mentioned so far can
supplement an interview but can and should never replace it. These instruments are
proven to be highly useful for research purpose, to have an idea about the baseline
severity of gambling and to monitor the progress with treatment.

Gambling Disorder
Table 1: Instruments for screening and diagnosis of gambling disorder

Instrument Number of items Time to administer
Screening instruments
Lie/Bet Two items; "yes/no" response One-minute interview
options
South Oaks Gambling Screen 20 scored items 10- to 20-minute paper and
(SOGS) pencil
Massachusetts Gambling 14-item questionnaire; seven Five- to 10- minute paper
Screen (MAGS) items are scored and pencil
NODS-CLiP Three items; "yes/no" One-minute interview
response options
NODS-PERC Four items; "yes/no" One-minute interview;
response options intended for use in clinical
settings
Brief Biosocial Gambling Three items; "yes/no" One-minute interview
Screen (BBGS) response options
Diagnostic instruments
Gambling Treatment 142-item Gambling 30- to 45-minute paper and
Outcome Monitoring System Treatment Admission pencil questionnaire
(GAMTOMS) Questionnaire has a 10-item
measure of DSM-IV
diagnostic criteria
Diagnostic Interview for 20 diagnostic symptom items 30-minute interview
Gambling Schedule (DIGS) to measure the two DSM-IV
diagnostic criteria
3.2 Exploration for Co-Morbidity

Internationally, the co-occurrence between problem gambling and co-morbid
psychiatric conditions has been empirically examined in both epidemiological and
clinical samples. A systematic review and meta-analysis of co-morbid disorders in
population-representative samples of problem gamblers revealed high rates of
psychiatric disorders, including nicotine dependence (60%), alcohol and substance use
disorders (58%), mood disorders (38%) and anxiety disorders (37%). A recent meta-
analysis of 36 studies has reported a lifetime and current co-morbidity as ~75%. In
order of frequency co-morbid disorders are mood disorders (23%), alcohol use
disorders (21%), anxiety disorders (18%) and non-alcohol substance use disorders
(7%).33 Evidence suggests that the presence of co-morbid disorders in treatment-seeking
PGs is associated with an increased severity of gambling behaviour, gambling-related
consequences, psychiatric symptoms, impulsivity and other psychosocial
difficulties.34-36 The presence of co-morbid psychiatric conditions therefore has

implications for individual case formulation, treatment planning and selection, the
proposed objectives and expectations of the selected treatment, and the even length of
treatment. Psychiatric co-morbidity may also affect an individual's compliance with
treatment, the success of treatment, the likelihood of relapse and the number of
treatment attempts.37-38
Therefore following presence of disorders must be explored by clinical interview and (if
needed diagnostic instruments):
l Substance use disorders
l Mood disorders
l Anxiety disorders
The process of diagnosing these disorders is outside the purview of the chapter.
3.3 Exploration for Psychosocial Consequences
GD incurs a lot of negative effect on the individual and on the family-society. It has been
estimated that for one person suffering from GD, at least 10 people get affected by its
negative consequences.39 Exploration of negative consequences is mostly historical and
following dimensions must be incorporated:
l Legal
l Marital relationship
l Interpersonal relationship with significant others in the family
l Financial
l Occupational
l Overall quality of life
Gambling Treatment Outcome Monitoring System (GAMTOMS), as mentioned earlier
is a comprehensive instrument which can assess the adverse psycho-social effects of
gambling. This instrument can supplement the clinical history. Such an assessment
could be extremely helpful in planning treatment and to monitor the progress of it.
4. TREATMENT SETTINGS
Gambling disorder might be encountered both in the psychiatric or addiction treatment
clinic. The orientation and philosophy of these clinics are different. However, as GD is
currently a part of addictive disorder and most of the research conducted so far was
based on substance use disorder treatment clinics and done by a group of researchers
with substance use disorder orientation and allegiance, this clinical practice guideline
would be predominantly guided by addiction treatment principles. Although no
systematic assessment has been conducted so far, the usual locus for the treatment of
GD is the out-patient clinics. Inpatient treatment is most likely to take place if the
individual is hospitalized for another psychiatric disorder, including substance use

Gambling Disorder
disorders. Research had revealed that individual with either psychiatric or substance
use co-morbidity tends to have higher severity and poorer outcome for both gambling
and the other disorder.40-42
Following could be indications for inpatient treatment:
l Patients with depressive disorder and suicidality
l Patients with severe substance use disorders
l Poor social support
l Court mandated admissions
5. TREATMENT FOR GAMBLING DISORDER (GD) / PATHOLOGICAL GAMBLING
(PG)
Surveys in the general population indicate that only about 10% of those who are
suffering from GD seek formal treatment. Reasons for their non-treatment seeking are a
desire to handle their problem on their own, shame, and denial.43-44 Despite low
treatment seeking both direct and indirect evidence indicate that the recovery rate of
GD is around 30-40%. And most of the individual recovers without treatment from
professional sources. Hence GD is not always a chronic, persistent and severe
disorder.45 Moreover, it has been seen that individual with more legal complications,
preoccupation with gambling and with co-morbid mood disorders seeks treatment.46 In
depth interviews of those who were recovered had revealed use of behavioural
strategies like, engaging in activities incompatible with gambling and avoidance of
conditioned cues, which are quite similar with those who had undergone professional
treatment.47 These facts don't question the necessity for the treatment of GD rather point
towards some important considerations regarding those who seek treatment (the subset
of patients for whom this CPG is applicable):
l More severe form of GD (severity might be in terms of more psycho-social
consequences or presence of severe co-morbidity)
l Brief treatment model might aid in the self-recovery process of the individual
l It is important to dispel stigma and resultant myth regarding gambling
l There is always a hope for recovery
Goal of treatment for GD: Gambling as has been conceptualized as addictive disorder
the standard goal and standard outcome measure remain complete abstinence.
However, research does not support the contention that abstinence-based goals are
more advantageous than moderation goals.48 In fact, research has demonstrated the
viability of non-abstinent treatment goal and popularity of the same amongst those in
natural or treatment assisted recovery. A study conducted amongst the female with PG
in Australia has shown that those with older age and with a strong belief that complete
abstinence is not required for recovery opt for moderation as treatment goal.49

Nevertheless, the definition of moderation or non-abstinence is still a point of

contention and most of the treatment research in this area is based on complete
abstinence. Hence, in our CPG we recommend complete abstinence as the goal of
treatment for GD.
5.1 Pharmacological Treatment for GD
The different pharmacological approaches currently considered for GD derive from the
various psychopathological and phenomenological perspectives of the disorder. GD
may be considered as belonging to the impulse control or obsessive compulsive
spectrum, as a behavioural addiction or as the result of an emotional dysregulation
closely related to mood disorders. In the first case, pharmacological approach is based
on anti-obsessive or antidepressant drugs, in order to improve serotonergic
transmission. Drug dose is usually medium-high and the treatment lasts longer than in
depression. According to the second perspective, the most used compounds are opioid
antagonists, as in the treatment of alcoholism or other forms of addiction. In particular,
controlled studies have been conducted for naltrexone and nalmefene on larger
samples. In the third approach, therapy is based on mood stabilizers such as lithium and
atypical antipsychotics, as in the treatment of resistant depression and bipolar disorder.
We shall be discussing the efficacy of these groups of agents subsequently.50
The outcome measures decided for each study are also based on the rationale behind
using that group of medication. For example, trials of antidepressants had used
reduction Y-BOCS (gambling), anxiety-depression rating as the primary outcome,
whereas trials with opioid antagonists mostly had used reduction in gambling frequency
and dollars lost in gambling as primary outcome measures. Secondary outcome mostly
was change in the CGI scale. Details of all pharmacological treatment trials have been
summarized in Table 2.
5.1.1 Opioid antagonists:51-55
The trial of this group of drugs could be justified by conceptualizing GD as behavioural
addiction, which is the most acceptable and empirically validated stance at the present
moment. Most of the studies have tried naltrexone and only few are on nalmefene.
Overall, Naltrexone has shown more consistent efficacy compared to SSRIs in reducing
gambling urges and excitement related to gambling. Naltrexone does not usually result
in intolerable side effects despite the dosage of naltrexone which was used in these trials
was more than that is used for alcohol or opioid dependence. Studies published so far
have been discussed in tabular format.
5.1.2 Antidepressants:56-62
A variety of antidepressant drugs have been studied and tested for the treatment of GD
banking on the hypothesis that GD could be a disorder of obsessive-compulsive
spectrum. The efficacy of both SSRI and non-SSRI group of drugs have been

Gambling Disorder
investigated. Amongst SSRI fluvoxamine, paroxetine, and escitalopram have shown

some promising results, whereas results for sertraline and bupropion are negative. Most
of the trials were double blind and randomized but sample size ranged from 15-76.
Duration of treatment ranged from 2-6 months.
5.1.3 Mood stabilizers:63-66
Mood stabilizers showed anti-impulsive properties as well as efficacy in reducing
craving and preventing relapse in different substance-related disorders. Considering
GD as disorder of emotional dysregulation and lying on the mood disorder spectrum,
several studies have been conducted to evaluate their usefulness in the treatment of GD.
Trial with lithium carbonate was shown to be effective. However, this study was
conducted in patients with bipolar disorder. Studies using olanzapine did not find it
superior than placebo.
5.1.4 Other group of medications:67-74
Clinical trials have also been conducted with agents which modulates the glutamatergic
neurotransmission. Glutamatergic neurotransmission-modulating agents which are
tried in GD include N-acetylcysteine (NAC), memantine, amantadine, acamprosate,
topiramate, lamotrigine, baclofen, and modafinil. Manipulation of glutamatergic
neurotransmission is a relatively young but promising avenue for the development of
improved therapeutic agents for the treatment of drug and behavioural addictions.
Substantial evidence has accumulated indicating that ligands acting on glutamatergic
transmission are also of potential utility in the treatment of drug addiction. Evidence is
overall mixed. However, NAC is emerging as a promising agent.
Table 2 : Pharmacological treatments for gambling disorder (GD)

Study N Dose/day; Design Results
Duration of use
Opioid antagonists (naltrexone/nalmefene)
Kim et al. 89 Naltrexone Randomized Double- Outcome: gambling frequency
200151 mean dose blind Placebo- and loss of dollar
188mg/day; controlled Naltrexone is significantly
duration: 12 weeks superior to placebo
Grant et al. 77 Naltrexone Randomized Double- Outcome: Scores of urge and
200852 dose range: blind Placebo- behaviour subscales of the PG-
50-150mg/day; controlled YBOCS and Gambling symptom
duration: 18 weeks assessment scale
Naltrexone is significantly
superior to placebo


Duration of use
Toneatto et 52 Naltrexone Randomized Double- Outcome: gambling frequency
al. 200953 mean dose: blind Placebo- and loss of dollar
59mg/day; controlled Naltrexone is significantly
duration: 11 weeks superior to placebo
Grant et al. 207 Nalmefene dose Randomized Double- Outcome: gambling frequency
200654 range: blind Placebo- and loss of dollar
25-100mg/day; controlled Naltrexone is significantly
duration:16weeks superior to placebo
Grant et al. 233 Nalmefene dose Single blind for 1 Outcome: Outcome: Scores of
201055 range: week with placebo urge and behaviour subscales of
20-40mg/day; then the PG-YBOCS
duration:16weeks Double-blind for Nalmefene 40?mg/day is
next 15 weeks significantly superior to placebo
Antidepressants
Hollander et 15 Fluvoxamine (SSRI) Double-blind cross- Outcome: overall score in PG-
al. 200056 mean dose over YBOCS and PG-CGI
195mg/day; placebo-controlled Fluvoxamine is superior to
duration: 16 weeks placebo
Blanco et al. 32 Fluvoxamine (SSRI) Randomized Double- Outcome: reduction in money
200257 mean dose blind Placebo- and time spent in gambling per
200mg/day; controlled week
duration: 24 weeks Fluvoxamine is not significantly
superior to placebo
Kim et al. 45 Paroxetine (SSRI) Randomized Double- Outcome: scores on Gambling
200258 with dose range: blind Placebo- symptom assessment scale and
20–60mg/day; controlled CGI
duration: 8 weeks Paroxetine is superior to
placebo
Grant et al. 76 Paroxetine (SSRI) Randomized Double- Outcome: overall score in PG-
200359 10–60mg/day; blind Placebo- YBOCS and Gambling
duration:16 weeks controlled symptom assessment scale
Paroxetine is not significantly
superior to placebo
Saiz-Ruiz et 60 Sertraline (SSRI) Randomized Double- Outcome: Criteria for Control
al. 200560 50–150mg/day; blind Placebo- of Pathological Gambling
duration: 24 weeks controlled Questionnaire (CCPGQ)
Sertraline is not significantly
superior to placebo
Grant et al. 13* Escitalopram (SSRI) Open label trial for Outcome: overall score in PG-
200661 mean dose 12 weeks then YBOCS and score on HAM-A
25mg/day; Double-blind Escitalopram is superior to
duration: 20 weeks Placebo-controlled placebo
for 8 weeks
*Patients with co-morbid anxiety

Gambling Disorder

Duration of use
Black et al. 39 Bupropion (NDRI) Randomized Double- Outcome: Yale-Brown
200762 mean dose blind Placebo- Obsessive-Compulsive Scale
325mg/day; controlled modified for PG, the Gambling
duration: 12 weeks Severity Assessment Scale, the
Clinical Global Impression
Improvement
Bupropion is not significantly
superior to placebo
Mood stabilizers
Hollander et 40* Lithium carbonate Randomized Double- Outcome: total pathological
al. 200563 mean dose blind Placebo- gambling scores on the Yale-
1170mg/day; controlled Brown Obsessive Compulsive
duration: 10 weeks Scale and Clinical Global
Impression severity of
pathological gambling scale
Clinical Global Impression
severity of pathological
gambling scale
Lithium is significantly superior
to placebo
Berlin et al. 42 Topiramate Randomized Double- Outcome: change in the
201364 25–300mg/day blind Placebo- obsessions subscale of the Yale-
;duration: controlled Brown Obsessive-Compulsive
14 weeks Scale Modified for Pathological
Gambling and scores on
Barratt's impulsiveness scale
Topiramate is not significantly
superior to placebo
McElroy et 42 Olanzapine Randomized Double- Outcome: change in the
al. 200865 2.5–15mg/day; blind Placebo- obsessions subscale of the Yale-
duration:12 weeks controlled Brown Obsessive-Compulsive
Scale Modified for Pathological
Gambling
Olanzapine is not significantly
superior to placebo
Fong et al. 23 Olanzapine Randomized Double- Outcome: self-reported urges
200866 2.5–10mg/day; blind Placebo- for gambling, frequency of
duration: 7 weeks controlled gambling behaviour, and self-
reported mood and anxiety
levels
Olanzapine is not significantly
superior to placebo
*Patients with bipolar comorbid


Duration of use
Other medications
Zack & 20 Modafinil: Placebo-controlled, Outcome: differential effects in
Poulos, 200mg/day double-blind, the high-impulsive (H-I) vs. low-
200867 counterbalanced, impulsive (L-I) PGs
repeated measures In H-I subjects, the drug
design decreased desire to gamble,
salience of Gambling words,
disinhibition and risky decision-
making; worsening in the L-I
subgroup
Grant et al. 27 N-acetyl cysteine Open label trial for 8 Outcome: Yale Brown
200768 (NAC) mean weeks then double Obsessive Compulsive Scale
effective dose of blind trial for the Modified for Pathological
NAC was next 6 weeks Gambling [PG-YBOCS] total
1477mg/day); score
duration: 14 weeks NAC is superior to placebo
Grant et al. 28* N-acetyl cysteine Randomized Double- Outcome: scores on Fagerström
201469 (NAC) dose: 1200- blind Placebo- test for nicotine dependence
3000mg/day; controlled and Yale Brown Obsessive
duration:12 weeks Compulsive Scale Modified for
Pathological Gambling [PG-
YBOCS] total score
During the 3-month followup,
NAC was superior to placebo
on PG severity and NAC
facilitates long-term behavioural
therapy
Grant et al. 29 The mean effective Open label study Outcome: Yale Brown
201070 dose of memantine Obsessive Compulsive Scale
was 23mg/day; Modified for Pathological
duration: 10 weeks Gambling [PG-YBOCS] total
score and also gambling
frequency/duration
Improved scores than the
baseline
Thomas et al. 17# The mean dose of Open label placebo Outcome: Yale Brown
201171 amantidine: controlled study Obsessive Compulsive Scale
200mg/day Modified for Pathological
Gambling [PG-YBOCS] total
score and daily expenditure
reduction
Amantadine is better than
placebo
*With nicotine dependence #Patients with Parkinson's disease

Gambling Disorder

Duration of use
Black et al. 26 Dose of Open label placebo Outcome: Yale Brown
201172 Acamprosate: 999- controlled study Obsessive Compulsive Scale
1998mg/day; Modified for Pathological
duration: 10 weeks Gambling [PG-YBOCS] total
score
Acamprosate is well tolerated
and may be effective in the
treatment of PG (not statistically
significant than placebo)
Dannon et 17 Acamprosate vs. Open label trial Outcome: diagnosis as per
al. 201173 bacofen; duration: No placebo semi-structured instrument
6 months No improvement with either
acamprosate or baclofen
Grant et al. 24 Tolcapone dose: Open-label trial Outcome: reductions in GD
201374 100mg/day; explored severity, depression, anxiety
duration: 8 weeks and disability and improvement
in quality of life
Tolcapone is better than
placebo
Recommendation
l Naltrexone can be considered as the first line pharmacological treatment for
gambling disorder (GD). Dosage required could be more than the usual dose used
for the treatment of alcohol dependence. [A]
l N-acetyl-cysteine (NAC) could be another promising first line agent following
naltrexone [A]. Dosage to be administered ranged from 1200-3000 mg/day. [B]
l Second line agents: fluvoxamine (~200 mg/day) [B], paroxetine (~50 mg/day) [B],
memantine (~20mg/day), tolcapone, and acamprosate [C].
l Escitalopram could be an option for those with co-morbid anxiety disorder [B].
l For individual with high impulsiveness modafinil could be an alternative treatment
option [B].
l Response to treatment could be seen between 1-8 weeks, depending upon the type
of medication (opioid antagonist ~1 week; NAC ~8 weeks). Any medications must
be continued for this duration before changing it. Duration of treatment though not
well defined, medications could be safely used for 6 months.
Nalmefene, though found out to be effective in randomized double blind trials [A], is
not available in India.

Key uncertainties
l Duration of treatment is not defined.
l Treatment effect or strategies for those with co-morbid substance use disorders needs
to be evaluated.
l Though there few narrative reviews, no meta-analysis has been conducted till date.
5.2 Psychosocial Treatment for Gambling Disorder (GD)
Research in the area of psychological treatment for GD is perhaps better developed as
opposed to the pharmacological treatment. Several treatment options for gamblers have
been explored, ranging from self-help and peer support, to brief and motivational
interventions, to more intensive therapy approaches. Involvement in peer support
programs seems to be optimal when combined with professional treatment; however,
engagement and retention in peer support is limited. In majority of the studies, primary
outcomes were measures of gambling symptom severity, financial loss from gambling
and frequency of gambling. Secondary outcomes were occurrence of pathological
gambling diagnoses and depression and anxiety symptoms. Retention in the treatment,
one of the significant determinants of the outcome for any psychological treatment, is
another parameter which has been frequently studied. Overall retention rates range
from 50% to 90%. Treatment effects were defined by comparisons between therapy and
control conditions at post-treatment assessments (conducted from 0 to 3 months
following completion of treatment) and follow-up assessments (conducted from 9 to 12
months following completion of treatment). Details of all psycho-social interventions
have been reviewed in Table 3.
5.2.1 Gamblers Anonymous (GA)75
GA which is modeled on Alcoholics Anonymous 12-step programs strongly advocates
complete abstinence from gambling. Like its sister programs, GA has adopted the
disease model and views disordered gambling as a lifelong affliction that can be
controlled via gambling abstinence, but not cured. Gamblers Anonymous were started
in 1957 in Los Angeles, CA, USA, and are now operating in at least 55 countries
worldwide (http://www.gamblersanonymous.org/mtgdirTOP.html.). The groups
promote a sense of common purpose and understanding and reinforce each
consecutive day of abstinence from gambling. As with Alcoholics Anonymous, periods
of success are marked with celebrations and rewards.75 Twelve-step-facilitation (TSF) is a
professionally led structured form of psychological intervention derived from the
treatment philosophy of 12 step programs and aims increasing referral to, involvement
in, and understanding of 12 step programs. TSF has been tried for gambling also. The
effectiveness studies are mentioned in the Table 3.

Gambling Disorder
5.2.2 Cognitive behaviour therapy (CBT)76-86

It is one of the widely researched and practiced forms of psycho-social intervention.
CBT is conducted by a trained professional and is an intensive psychological treatment.
Its treatment model focuses specifically on modifying distorted cognitions associated
with gambling, including overestimating probabilities of winning, illusions of control
over the outcome of a gamble, the belief that a win is due after a series of losses (i.e.,
thegambler's fallacy), and memory biases in favor of remembering win. The cognitive
errors have been enumerated in the Panel 4. CBT also includes problem-solving
training, social skills training, and relapse prevention. Behavioural models
conceptualize gambling disorders as learned patterns of reinforcement within a
functional framework. Continued gambling behaviours stem from a variable pattern of
reinforcement with respect to antecedents (e.g., external gambling cues, positive or
negative emotions), behaviours (e.g., chasing of losses, strategizing to attain money),
and consequences (e.g., financial loss). CBT treatments focus on modifying one or more
components of this functional relationship in order to modify the learned patterns.
Although a small number of trials have evaluated the efficacy of a purely cognitive
approach, the largest number and the most rigorously designed trials have evaluated a
combined CBT model. The rubric of CBT, however, encompasses a wide range of
therapeutic approaches.
5.2.3 Brief and motivational interventions 87-95
As already mentioned elsewhere in this CPG, treatment seeking is very low in GD.
Additionally those who are seeking either professional treatment or attending GA
almost half of them could not be retained in the treatment or in the self help groups.76-78
This poor retention rate is perhaps a reflection of internal ambivalence for change or is
indicative of treatment seeking due to external factors like persuasion by family and
friends. Moreover, poor long term retention reiterates the need for brief intervention.
Motivational approaches attempt to address client ambivalence towards change, for
example by weighing the advantages and disadvantages of changing their gambling
behaviour. Some motivational therapies provide personalized and/or normative
feedback. Motivational approaches have also been explored as an avenue to engage
problem or at-risk gamblers who have not yet met diagnostic criteria for gambling
disorder, in an attempt to prevent escalation of gambling behaviour and related negative
consequences.75
5.2.4 Other self-help measures88-90
Some individuals may prefer individual, self-directed options such as bibliotherapy (eg,
workbooks), Internet-based interventions relative to GA, or in-person therapy. The
workbook materials have been evaluated as stand-alone interventions and in
combination with telephone or in-person support. Evidence base for bibliotherapy
though minimal has been mentioned in the Table 3.

5.2.5 Family therapy96

Advances in family therapy interventions for treating substance abuse problems have
been adapted for gambling disorders. A self-help workbook of the Community
Reinforcement and Family Therapy (CRAFT) model, adapted for gambling, has been
evaluated in two randomized controlled trials. In CRAFT, family members are trained to
use behavioural principles to reinforce non-gambling behaviour and not to reinforce
inadvertently the gambling behaviour in individuals who are not addressing their
gambling problem.
5.2.6 Combined psychosocial approach97-100

Most commonly combined psychosocial therapies are motivational intervention/brief
therapy with an intensive psychological treatment like CBT. This makes intuitive sense
to combine these forms of treatment because of their putative additive effects; i.e.,
motivational intervention will improve treatment retention which is an important
mediator in the effectiveness of any intensive therapy. Though not a usual part of
standard CBT, cue exposure therapy is sometime combined with traditional CBT.[2]
Another combination which is widely practiced for its pragmatic value is combining
motivational therapy with bibliotherapy (like proving CBT workbooks). Sometime
online or telephonic brief sessions or e-mail reminders are used in conjunction with
other forms of intervention.
There are a couple of narrative reviews in the area of psychological treatment for GD.
However, we could locate only one meta-analysis conducted by Cochrane
collaboration. Eleven studies compared CBT with control and comparisons at 0 to 3
months post-treatment showed beneficial effects of therapy that ranged from medium to
very large. Only one study compared groups at 9 to 12 months follow-up and produced
smaller effects that were not significant. Four studies of motivational interviewing
therapy were identified and mainly considered samples demonstrating less severe
gambling (relative to studies of pathological gamblers). Data suggested reduced
financial loss from gambling following motivational interviewing therapy at 0 to 3
months post-treatment. Studies compared groups at 9 to 12 months follow-up and found
a significant effect of motivational interviewing therapy in terms of frequency of
gambling, with comparisons on other outcomes that were not significant. One study (n
= 18) considered another psychological therapy (i.e.Twelve-Step Facilitated Group
Therapy) and suggested beneficial effects in terms of most outcomes at 0 to 3 months
post-treatment. This review supports the efficacy of CBT in reducing gambling
behaviour and other symptoms of pathological and problem gambling immediately
following therapy. However, the durability of therapeutic gain is unknown.

Gambling Disorder
5.3 Combined Psychotherapy and Drug Treatment

Combination of both modalities of treatment has been rarely studied systematically. A
recent randomized controlled trial compared the effectiveness of combined
escitalopram (20mg/day) and CBT versus CBT alone for the treatment of GD, and found
no evidence for improved outcomes among those receiving both escitalopram and CBT
in comparison to those receiving CBT only(Jun. 2013 http://clinicaltrials.gov/ct2/
show/NCT00927563). In another study combined NAC and imaginal desensitization
therapy has been found to reduce nicotine dependence and improve longer-term GD
treatment outcome. 69 Further research into combined behavioural and
pharmacotherapy with respect to different medication types (e.g., opioid antagonists) is
needed.
Panel-4
Distorted cognitions in GD
Magnification of gambling skill
l Overrating one's ability to win at gambling
Superstitious beliefs
l Talismanic superstitions include beliefs that the possession of certain objects
increases the probability of winning (eg, ring, hat)
l Behavioural superstitions include beliefs that certain actions or rituals can
increase the probability of winning (eg, playing only certain slot machines or
placing smaller bets if they do not throw the dice themselves)
l Cognitive superstitions include beliefs that certain mental states can affect the
probability of winning (eg, prayer, hope, positive expectancies)
Interpretative biases
l Attributional biases refer to the tendency to overestimate dispositional factors
(e.g., skills, abilities) to explain wins and to underestimate situational factors
(e.g., luck, probability)
l Gambler's fallacy refers to the belief that a win is due after a series of losses
l Chasing refers to the belief that the only way to recover financial loss is to
continue to gamble
l Anthropomorphism is the tendency to attribute human characteristics to non-
animate or non-human gambling objects (e.g., slot machine, lottery card, bingo
card, horses)

l Learning from losses refers to the belief that continuing to gamble is highly
justifiable because losses are perceived as valuable learning experiences, which
can ultimately lead to winning
l Hindsight bias refers to retrospectively evaluating gambling decisions as correct
or incorrect on the basis of whether they lead to wins or losses
Temporal telescoping
l The belief that wins are actually nearer, temporally, than further, especially if the
gambling is relying on superstitious behaviour or gambling systems to win; the
gambler makes the additional assumption that they (rather than other gamblers)
will win, even if other gamblers have also incurred serious losses and are
expecting to win
Selective memory
l Selectively recalling wins, especially large ones, and having difficulty recalling
losses
Predictive skill
l Making gambling decisions on the basis of interpretations or meanings assigned
to subjectively salient or important cues; cues can be internal (e.g., bodily
perceptions, gut sensations, intuitions, feelings) or external (eg, omens, weather
phenomena, serendipitous events) or behaviour by other gamblers
Illusions of control over luck
l Luck can be perceived as an important variable and regarded as an
uncontrollable variable (ie, luck oscillates between periods of good and bad luck
and cannot be manipulated directly), a controllable variable (ie, luck can be
manipulated through superstitious behaviours or systems), a trait variable (ie,
people are characteristically lucky with certain games and unlucky with others),
or a contagion (ie, luck is affected by other areas of their life or by other people)
Illusory associations
l Perceiving illusory associations or assigning causality to salient features of the
environment believed to be associated with gambling outcomes (eg, noticing
more frequent winning at night, noticing that certain days of the week are more
likely to lead to wins, believing that watching a sports game on television will
favor a specific team)
Toneatto T, Ladoceur R. Treatment of pathological gambling: a critical review of
the literature. Psychol Addict Behav. 2003; 17:284-92.19

Gambling Disorder
Table 3 : Psychosocial therapies for gambling disorder (GD)

Study N Number and Design Results
duration of
sessions
Cognitive behaviour therapy (CBT) and CBT-plus- other intervention
Sylvain et al. 40 enrolled 30 sessions with Cognitive therapy Outcome: Gambling symptom
(1997)76 14 vs. 22 in six-month follow- (CT) + relapse assessment scale to measure
treatment up prevention vs. wait gambling severity
groups list (WL) CT is better than WL control
completed Randomized
controlled trial
Ladoucer et 88 enrolled 20 sessions with Cognitive therapy + Outcome: Gambling symptom
al. (2001)77 35 vs. 59 in 12-month follow- relapse prevention assessment scale to measure
treatment up vs. wait list gambling severity
groups Randomized CT is better than WL control
completed controlled trial
Ladouceur et 81 enrolled 10 weeks with Group cognitive Outcome: Gambling criteria
al. (2003)78 34 vs. 46 in two-year follow- therapy (GCT) + based on structured interview
treatment up relapse prevention CBT vs. WL: 65 percent no
groups vs. wait list longer met PG criteria vs. 20
completed Randomized percent on wait list
Echeburua et 64 enrolled Six weeks with Groups: Stimulus Outcome: Abstinence from
al. (2000)79 50 12-month follow- control with in vivo gambling or reduction in
completed up exposure and relapse gambling frequency
prevention (SCERP), SCERP>CT=Combined
cognitive treatment
restructuring,
combined treatment
and wait list
Milton et al. 40 assigned Eight sessions Individual CBT vs. Outcome: Gambling symptom
(2002)80 to treatment; with a 9 month CBT + interventions assessment scale to measure
20 follow-up to improve treatment gambling severity and treatment
completed compliance retention
(motivational Addition of motivational
interventions) intervention improves treatment
Randomized
controlled trial
Melville et Group CBT: Two 90-minute Group CBT, group + Outcome: Gambling criteria
al. (2004)81 13 vs. sessions each interactive written based on structured interview
group + week for eight assignments and treatment retention
interactive weeks (mapping) vs. wait- Combined treatment is better in
written list control terms of reduction of GD
assignments: Combined group symptoms
19; (>80% included co-morbid Co-morbidity reduced treatment
females) mood disorders retention


duration of
sessions
Petry et al. 231 Eight sessions Manualized CBT in Outcome: Abstinence from
(2006)82 enrolled; with one-year individual counseling gambling or reduction in
181 follow-up vs. CBT workbook vs. gambling frequency
completed GA referral At the end of the session:
Randomized Individual CBT> CBT
controlled trial workbook> GA referral
At the end of 1 year: no
difference amongst treatment
groups
Wulfert et al. CMBT 16 sessions with Cognitive- Outcome: Gambling criteria
(2006)83 group: 9 three-, 6 and 12- Motivational based on structured interview
TAU group: month follow-up Behaviour Therapy CMBT>TAU
8 (100 (CMBT) vs. treatment Improvement maintained at 12
percent as usual (TAU) months follow up
male) Randomized
controlled trial
Echeburúa, 44 enrolled 20 sessions with Behaviour therapy vs. Outcome: gambling frequency,
Gómez, & 41 three-, six and cognitive money lost in gambling
Freixa, completed 12-month follow- restructuring/relapse CBT is better than TAU
(2001)84 up prevention Efficacy is less robust at 6 and
Psycho-education, 12 months
stimulus control,
gradual exposure and
relapse prevention
Jimenez- 352 males 16 weekly group Comparison of Outcome: Scores on the

Murcia et al., CBT sessions CBT+ERP vs. CBT Symptom Checklist-Revised
201285 alone (SCL-90-R) and the South Oaks
Quasi-experimental Gambling Screen (SOGS); rate
non-randomized of relapse
study No difference between the
groups
CBT+ERP: poorer retention rate
Smith et al., 87 (CT= 44, 1, 3, and 6 differential efficacy of Outcome: rated by participants
201586 ET=43); month follow-up CT and Exposure using the Victorian Gambling
completers: therapy (ET) for adult Screen (VGS)
CT=30, problem gamblers Both groups experienced
ET=21) Randomized comparable reductions
controlled trial (improvement) in VGS scores
both at the end and after 12
months

Gambling Disorder

duration of
sessions
Brief intervention or motivational interviewing (-plus-other psychological therapy)
Dickerson et 29 enrolled Providing CBT CBT workbook vs. Outcome: not well defined
al. (1990)87 based workbook workbook + a single Both groups improved at six
and single in- in-depth interview months
depth session
Hodgins et 102 Single session of CBT workbook vs. Outcome: Clinical global
al. (2001)88 enrolled 85 motivational workbook + impression modified for PG
available at enhancement motivational No statistical difference
12 months enhancement between motivational
intervention via enhancement and workbook
telephone vs. wait list Both better than WL
(WL)
Hodgins & Unclear Single session Single-session Outcome: Gambling frequency

Holub, with 12 months motivational and money spent in gambling
(2007)89 follow up interview (MI) with MI> Self-help workbook
self-help workbook
vs. workbook alone.
Hodgins et 169 Mailings done Relapse-prevention Outcome: criteria met in South
al. (2007)90 enrolled once for first bibliotherapy – single Oaks Gambling Screening
142 group (n=85) vs. mailing vs. repeated questionnaire (SOGS)
available at seven mailings mailings over a 12- The repeated-mailing group
12- month for second group month period improved more than the single-
follow-up (n=84), with 12- mailing group but not
month follow- up significantly
Carlbring & 66 enrolled Six-, 18- and 36- Web-based CBT with Outcome: criteria met in South
Smit, 60 with month follow up telephone support Oaks Gambling Screening
(2008)91 post- and online workbook questionnaire (SOGS)
treatment materials vs. waitlist Intervention group: moderate to
data control large improvements maintained
at 36-month follow-up
Hodgins et 314 Six-, nine- and Motivational Outcome Gambling frequency

al. (2009)92 enrolled 12-month follow- interview + mailed and money spent in gambling
267 up completed self-help workbook MI+ workbook=Workbook
completed vs. six-week waitlist only> WL
12-month control or workbook-
follow-up only control
Diskin & 81 enrolled One-, three-, six- Single in-person Outcome: Gambling severity
Hodgins, 69 and 12- month motivational MI significantly better than
(2009)93 completed follow-up interviewing vs. control interview
12-month control interview Improvement persisted after 12
follow-up months
(>40%
female)


duration of
sessions
Petry et al. 117 Nine-month Four conditions: Brief All treatment conditions
(2009)94 enrolled follow-up advice vs. provided significant symptom
114 motivational improvement although MET had
completed enhancement therapy the most significant effect
Week 6 (MET) vs. MET + relative to the control group
evaluation CBT vs. no-treatment
113 control
completed
9-month
follow-up
Carlbring et 150 Group CBT: 12 Group CBT (eight Outcome: severity of PG,
al. (2010)95 enrolled sessions sessions) vs. symptoms of anxiety and
MI: 4 sessions motivational depression
Six- and 12- interviewing (four CBT=MI>Control group
month follow-up sessions) vs. no
treatment control
group
Gamblers Anonymous (GA)/Twelve-step facilitation (TSF) [-plus- other psycho-social interventions]
Grant et al. 68 patients Six sessions of Imaginal Outcome: Yale-Brown
(2009)97 intervention desensitisation plus Obsessive Compulsive Scale
motivational Modified for Pathological
interviewing (IDMI) Gambling total scores, gambling
vs. Gamblers urges and gambling behaviour
Anonymous IDMI>GA
Those who did not respond to
GA, responded later to IDMI
Stewart et al. 232 One and 2 year Retrospective and Outcome: abstinence from
(1988)98 follow up prospective arms of gambling
GA attendees Rate of abstinence: 8% of all
Observational study comers at one year from first
attendance and by 7% at two
years
Toneatto & CBT:65 CBT/TSF: 8 CBT vs. TSF Outcome: Key gambling
Dragonetti, TSF:61 sessions each variables (eg, frequency,
(2008)99 abstinence rates, money
wagered)
TSF=CBT
Participants who attended more
sessions and chose an initial
abstinent treatment goal
appeared to achieve better
outcomes

Gambling Disorder

duration of
sessions
Marceaux TSF 6 months follow Group based CBT vs. Outcome: number of DSM-IV
et al. (n = 11), up TSF vs. WL criteria met, perception of
(2011)100 CBGT- control/self-efficacy, desire to
mapping (n gamble, and frequency of
= 18), and gambling episodes
Wait-List CBGT-mapping and TSF had no
control significant differences on any
(n = 9) outcome measure at follow-up
assessments
Gamblers Anonymous (GA)/Twelve-step facilitation (TSF) [-plus- other psycho-social interventions]
Hodgins et 186 Three- and six- Intervention groups Outcome: gambling frequency
al. (2007)96 enrolled month followup (based on CRAFT): Intervention groups had less
Self-help workbook days gambled but behavioural
vs. workbook + principles too complicated for
telephone support vs. family members to implement
control group
Recommendations
l In depth motivational intervention (MI) or short term (~4 sessions) motivation
enhancement therapy could be first line treatment options as a sole form of treatment
[A] or brief motivational intervention could be used in conjunction with other forms
of intensive interventions (especially CBT) to improve treatment retention [A].
l More intensive intervention especially CBT could be considered for long term
engagement [A]. Number of sessions could range from 10-30 (mean 20) [A]. CBT
could be delivered in both individual and group format [A]. Components of CBT
includes: cognitive restructuring, relapse prevention [A], skill training, and
behavioural interventions (like cue conditioning/extinction) [B].
l Bibliotherapy (proving workbooks) could be used along with either MI or CBT [B].
l Second line therapy options could be: twelve step facilitation (TSF) [A], Exposure
based therapy [B], and family therapy [C].Family therapy (CRAFT) could be useful
when the individual is not ready to seek treatment.
l Brief telephonic MI could be an option for those not willing to commit for long term
engagement or not willing to come to treatment facilities [B].
l Combination of N-acetyl-cysteine with exposure based therapy might have some
additive effect [B].
l GA referral unlikely to be effective alone, if not coupled with other professionally led
interventions [A].

l Because of the lack of empirical evidence, therapy for GD with a co-morbid

psychiatric disorder is still speculative. CBT could be an option [B].
The overall empirical evidence for the efficacy of psychological intervention in terms of
both quantity and quality of studies is better than pharmacological treatment. Hence, it
must be offered to all patients seeking treatment for GD.
Key uncertainties
l Durability of the effectiveness of psycho-social intervention is still a matter of debate
l Co-morbidity in GD is exceptionally common but no studies so far have addressed
this important issue systematically.
l Essential components of CBT need to be incorporated are still elusive.
l Feasibility, and efficacy of combined drug and psychological therapy needs to be
investigated in the future
l Countries like India in which majority of the treatment of substance use disorder is
clinic based and where there is a substantial scarcity of mental health professionals,
effective delivery of psychosocial management remains elusive.
l Cost effectiveness of these psychosocial interventions has not been researched
extensively.
6. CAVEATS OF THE PROPOSED GUIDELINE
Some research gaps have already mentioned in the section of key uncertainties.
However, in our mind there are other limitations which must have been kept in mind
while following and analyzing the index guideline. This practice guideline is purported
to help clinicians to manage patients attending their clinics. However, the abysmally
low treatment seeking might raise doubt regarding its pragmatic utility.43 Research
directed towards exploring the reasons behind low treatment seeking and improving
the same must be undertaken in near future. The second problem which could make this
guideline ineffectual is the problem of poor treatment retention.101Though there has
been some evidence that adding motivational interviewing could improve treatment
retention it needs to be replicated and systematically researched to find out other
strategies. Thirdly, combination of drug and psycho-social intervention which is
perhaps the most widely practiced strategy for the management of GD has been studied
minimally. Due to the lack of empirical validation, the effectiveness of this most
commonly practiced modality of treatment in real world setting could not be
commented upon. Fourthly, the psychological interventions which have maximum
empirical support are labor intensive and require special expertise. The existing
resources which are already struggling to keep up with the treatment of substance use
disorders might face further difficulty if 'burdened' with the challenge of treating
behavioural addiction too. This could question the practicability of these intensive
Gambling Disorder
interventions. Next, this guideline is based on the literature from the West. The
generalizability of such recommendations for our Indian population might be debated.
However, in absence of any treatment related research from India, we did not have any
better alternative than to extrapolate our recommendations from the Western literature.
Lastly, The Pathways Model explicated by Blaszczynski & Nower102 (although not as yet
fully validated) hypothesizes three routes into disordered gambling. Individuals in the
first group have no predisposing vulnerabilities; rather their gambling problems have
been conditioned by the psychological properties of the games themselves, and
perhaps by the experience of a 'big win' early in their gambling careers. The second
subgroup is prone to depression or anxiety, and these individuals begin gambling as a
means of escape or to otherwise alleviate these emotional difficulties. The third group
present with antisocial and impulsive tendencies, accompanied by neuropsychological
evidence of frontal cortex involvement. This model indicates that there could be an
opportunity for patient treatment matching. This area needs to be explored in the future.
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PATHOLOGICAL INTERNET USE
(“INTERNET ADDICTION”)
Prabhat Chand
Arun Kandasamy
Pratima Murthy
On behalf of
2016
Pathological Internet Use (“Internet Addiction”)
CONTENTS
Executive Summary
1. Introduction
2. Assessment
2.1 Assessment of Internet use
2.2 Assessment of comorbidity
2.3 Assessment of temperament
3. Management
3.1 Psychological Intervention
3.1.1 Cognitive Behaviour Therapy
3.1.2 Others
3.1.3 Effectiveness
3.2 Pharmacological
3.2.1 Anti-depressants
3.2.2 Stimulants
4. Psychological versus Pharmacological
5. Conclusion

EXECUTIVE SUMMARY
The literature regarding Internet addiction or pathological Internet use has been
increasing very fast along with increasing presence of Internet dependent activities in
the day-to-day life. There are different terms being used by different researchers about
excessive use of Internet i.e. pathological Internet use, compulsive Internet use,
problematic Internet use, Internet addiction, Internet dependency etc. The common
theme in all these terminology is inability to control one's use of the Internet which
leads to negative consequences in daily life. Disagreement regarding diagnostic criteria
and the lack of large epidemiological studies have resulted difficulty in establishing true
prevalence as well as assessment of pathological Internet use.
Assessment of temperament and comorbidities along with the nature of Internet use is
essential in the clinical practice. Excessive Internet use can also be expression of
ongoing emotional difficulty and ongoing poor coping mechanism. There is lack of
evidence based research in the management of Internet addiction. Cognitive
behavioural therapy for Internet addiction (CBT-IA) has been commonly used in clinical
settings. The initial stage of CBT-IA is on modifying the behaviour i.e. setting up realistic
goals, daily log of Internet use, structuring use, creating a new schedule and to learn to
control Internet usage. The second stage aims at reducing maladaptive cognitions. The
last stage focusses on real problems existing in their lives that lead to addiction. Various
other types of psychological interventions like Reality Therapy, Short term treatment of
Internet and computer addiction (STICA) has also been proposed.The pharmacological
treatment specific to Internet addiction are mostly based on case series and studies from
comorbid conditions like ADHD. Escitalopram, Bupropion, Methylphenidate has
shown promise. The effective therapy for IA/PIU needs an individual approach and best
results are expected on combined psychological and pharmacological treatment.

1.INTRODUCTION
Pathological Internet use (PIU), also known as problematic Internet use (PIU), has been
increasingly reported by clinicians across the world. This rise of PIU and related
research is associated with the unprecedented growth and access to the Internet across
the world.1 At this point, neither the diagnosis of PIU nor Internet addiction (IA) appears
in any official diagnostic system as a number of researchers feel this as a manifestation of
an underlying problem and the Internet is only a medium of expression. At the same
time, there are researchers who have argued that IA/PIU is a separate psychiatric entity
like other addictions or akin to compulsive-impulsive disorders.
Specifically symptoms of Internet addiction include a) preoccupation with Internet
activities; b) increasing tolerance; c) development of psychological dependency and
withdrawal symptoms; d) inability to reduce Internet use; e) Internet use to cope with
negative moods and reduce stress; and f) replacing other activities and relationships
with recurrent Internet use despite awareness of the deleterious consequences.2,3 Block
(2008) suggested four diagnostic criteria essential to a possible diagnosis of PIU as an
addictive behaviour: (1) excessive Internet use, often associated with a loss of sense of
time or a neglect of basic drives; (2) withdrawal, including feelings of anger, depression
and tension when Internet is not accessible; (3) tolerance, including the need for better
computer equipment, more software, or more hours of use; and (4) adverse
consequences, including arguments, lying, poor school or vocational achievement,
social isolation, and fatigue.4
2. ASSESSMENT
There are no standard diagnostic criteria for diagnosing IA/PIU. There are already about
50 screening/ diagnostic instruments for IA/PIU which different researchers have used
in their studies. A comprehensive review of these scales5 suggests that a few scales like
the Internet Addiction Diagnostic Questionnaire (IADQ)6, Internet Addiction Test
(IAT)3, Compulsive Internet Use Scale7 are frequently used while others have been
largely restricted to single research groups. Even for the frequently used scales, the
psychometric properties need further exploration. Most of them have been used for
research-based screening for IA/PIU. The prevalence estimate of IA/PIU varies
depending on types of criteria used.8 However, for a clinician, the clinical interview and
a thorough mental state examination still remains the gold standard for assessment.
Based on the evidence available to date, the authors would like to suggest a framework
for the assessment of pathological Internet use in this clinical practice guideline as
follows: (i) assessment of the Internet use, (ii) assessment of comorbidity, and (iii)
assessment of temperament.
2.1 Assessment of Internet use:
l Quantity of time and frequency of Internet use has been a common factor assessed

in traditional settings. Unfortunately this may not be of use in our setting because of
the Internet access through the mobile phone 24/7. Therefore it would be more
useful to give importance to the form and content of Internet use.
l Nature of Internet use: The assessment should be about essential and non-essential
or recreational use of the net. This information will be useful because it will help us
understanding whether there is any pathology at all, and if it is pathological, what is
the severity. This information needs to be incorporated into the management plan.
l Type of use: Whether the individual is gaming or gambling, using pornography
(Cyber sexual), getting into virtual relationships through social networking sites
(Cyber relationship), online shopping, bullying, hacking, etc.
l Factors motivating use: This information will be helpful to understand how Internet
is helping the patient psychologically. It will also provide insights into what are the
motivation factors that maintain the excessive use of the Internet. For example, an
adolescent who has difficulty in communicating in the real world feels more
confident of making relationships on social networking sites as the perceived threat
is lesser from a virtual world. Such motivations can guide therapy. Temperament
plays an important role in deciding the nature of games they choose.9
2.2 Assessment of comorbidity:
Psychiatric comorbidity can both be a cause and consequence of the IA/PIU. The
temporal relation is difficult to establish like in the case in other addictive disorders. But
gamers with IA/PIU have high risk of comorbidity like depression and anxiety.10-12 Carlie
et al.13 reviewed 20 studies and reported that among people with IA/PIU, 75% had
depressive symptoms, 57% had anxiety symptoms, 100% had ADHD symptoms, 60%
had OCD symptoms and 66% had aggression. Many studies have found association of
substance use disorders with IA/PIU14-16. In view of all the above findings, a thorough
psychiatric interview is advised in all the patients reporting with IA/PIU. Repetitive
strain injury (RSI), computer vision syndrome, fatigue, obesity etc. have been reported
with excessive computer use.
2.3 Assessment of temperament:
Certain personality traits may contribute to the initiation, and maintenance of IA/PIU17.
They need to be evaluated for both internalizing and externalizing temperaments. The
emerging evidences indicate that most of the adolescents presenting with IA/PIU has
significant temperamental issues which contribute to the abnormal behaviour.
This assessment will be helpful in reframing the problem, developing a rapport and
develop a holistic management plan rather than focusing on the IA/PIU.
3. MANAGEMENT
The research on psychological and pharmacological management for IA/PIU is

hampered by the inconsistencies in definition, lack of reliable criteria and inadequate

sampling methods. The preliminary evidence largely stems from open label trials, case
records and treatment responses of the comorbid disorders. In 2009, Petersen et al.18
argued that it is not possible to develop any suitable clinical recommendationsdue to
lack of studies. However over the last few years, a number of psychological and
pharmacological modalities has been tried to help people with IA/PIU.
3.1 Psychological interventions
Most of the intervention work has been developed in the area of psychological
interventions.
3.1.1. Cognitive Behaviour Therapy
Internet addiction has been proposed as a type of compulsive disorder. Hence
Cognitive Behaviour Therapy for Internet Addiction (CBT-IA) has been suggested as an
effective treatment for Internet addiction19. Internet being a daily necessity of modern
life, the focus of the CBT-IA is one of harm reduction rather than complete abstinence of
Internet use.
The CBT-IA as proposed by Young20 consists of three phases of treatment lasting for
approximately twelve weeks.
First Phase: Behavioural
The behavioural modification is the main goal of this phase. This consists of keeping a
diary of Internet use and other behaviours with a primary goal of abstinence from
problematic online use. The controlled use of Internet for work or other legitimate
purpose is allowed. Patient will keep a daily log of Internet usage i.e. day, duration,
event, activity, etc. The therapist, with inputs from the patient, builds up a structured
activity schedule incorporating other activities or new habits and streamlining the
online activity.Time management online and offline is the main focus.
Second Phase: Cognitive interventions
The target in this phase is to correct the maladaptive cognitions and triggers that initiate
excessive Internet usage. The distortive thoughts, i.e., “I am hopeless in my study but
only good at gaming” / “I am useless in offline but my online avatar (online game
character) can achieve everything”, etc. are often reported by patients. Pathological
Internet users may also develop thoughts that they are treated with dignity and respect
only in the virtual space than in the real world like school or home. They may feel
dissatisfaction or be unhappy with their real lives.
During cognitive therapy, the clinician identifies the distortions, challenges them and
allows re-scripting of the distorted thoughts. Cognitive restructuring allows the client to
re-evaluate how rational are his/her interpretations of these thoughts. For example, a
young boy having difficulty in making friends or socializing, uses massive multiple
online games to build his self-esteem, gradually realizes how his use of gaming is to
satisfy socializing emotional needs that are not fulfilled in real life.
Recognizing these patterns of faulty thinking helps the client to break the cycle of
Internet use and to restrict use of the Internet.
Third Phase: Harm reduction interventions
The associated problems related to personal, social and occupational functioning are
targeted in this phase. Identification and treatment of co-existing psychiatric and other
substance use helps in continued recovery and prevent relapse. The recovery process in
case of pathological Internet useis not just decreasing use but also addressing and
handling the underlying cause that leads to the compulsive use. Otherwise the chance
of relapse is very high.
Table 2 : Cognitive Behaviour Therapy for Internet Addiction (CBT-IA)20

(a) Practice the opposite: reorganization of the time or time management,
assessment of current habits and re-adapt to new time pattern. For example,
patient's Internet habit involves checking E - mail the first thing in the morning.
Suggest that the patient take a shower or start breakfast first instead of logging
on.
(b) External stoppers: Use external controls like alarm or prompters events to help
log off from the computer. Cultivate an alternative activity
(c) Set goals: Set reasonable and practical goals for use of Internet. Keep Internet
sessions brief and frequent. Aim is to have sense of self-control rather than
allowing the Internet to take control
(d) Abstain from a particular application: In case a particular application like chat,
game or networking is specifically more problematic and moderation has failed,
then abstinence from that is appropriate. He may use other activities like email
or web surfing. Abstinence is strictly advised for people who have past history of
drug or alcohol addiction problems.
(e) Reminder cards: The focus is here of self-reminding in a concrete way the five
major problem and five benefits for cutting down the usage.
(f) Personal inventory: Make an inventory of short term, medium term and long
term goals. Keep that in mind as a motivating factor to change current
behaviour.
(g) Support group: Self- help group
(h) Family therapy: Educate the family members, reduce the blame, improve on
communication and assist with addiction recovery.

3.1.2 Other Psychological Interventions

There are multiple other psychological interventions like Multi-level Counselling
Program (MLC), Social competence training (SoCo), Solution-focused Brief Therapy
(SFBT), Cognitive Therapy (CT), Reality Therapy (RT) that have used for the treatment of
IA. The MLC is usually a combination of different psychological therapieslike CBT &
Psychoeducation, CBT & parent training with medications etc. The reality therapy
proposed by Kim among Korean students, includes techniques such as: control theory,
five basic needs, total behaviour, friendly involvement, and making a plan, along with a
few components of CBT. In Germany, CBT based short term treatment of Internet and
computer addiction (STICA) consisting both individual and group therapy for four
months duration is proposed for IA. A recent pilot study describing the steps of STICA,
reported significant improvement in IA related symptoms among 42 outpatients.21 The
readers can go through an excellent review and meta-analysis of these studies by
Winkler 201322.
Table 3 : Short-term Treatment for Internet and Computer Game Addiction (STICA)21
Probatory Psychological diagnostic of IA

Anamnesis of current and life-time media use
Identification of problematically used online contents
Diagnosis of comorbid disorders
Assessment of psychopathological symptoms and
psychosocial resources
Initial stage Initializing trustful patient-therapist alliance and therapy

commitment
Assessment and enhancement of motivation for behavioural
change
Development of proximal and distal therapy aims
Psycho education
Behaviour modification Psycho education

Identification of triggers (situations, cognitions, beliefs,
emotions, and psychophysiological reactions) of Internet use
Develop of SORKC-schemes and cognitive restructuring
Development of an individual model of IA
Training module: discrimination of emotional states
Social skills training
Reestablishment of alternative behavioural strategies and
interests

Stabilization and Reestablishment of alternative behavioural strategies and

relapse prevention interests
Exposure training and habituation training
Individual relapse prevention, stopping techniques, and
emergency plans
3.1.3 Effectiveness
There is robust evidence to suggest the effectiveness of various forms of psychological
intervention for IA.The effect size of CBT alone is 0.84-2.13(95% CI) and other
psychological treatments is 1.12-2.67 (95%CI) indicating the effectiveness as well as no
significant differences between the interventions. CBT group performed significantly
better with regard to “time spent online” and recovery from depression compared to
other groups. A higher number of female participants, older patients, or an American
sample had larger effect sizes for some outcome variables.22
3.2. Pharmacological
Pharmacological treatment for IA is mostly extrapolated from the treatment of
comorbidities i.e. depression, ADHD or substance use. Recent neuroimaging studies
point towards the involvement of limbic and prefrontal cortex just as in other
addictions, indicating the possible effectiveness of anti-craving drugs like opioid and
glutamate antagonists.
3.2.1. Anti-depressants
Escitalopram in the dose range of 20-30 mg/day for 10 weeks in an open label study on
19 patients as well as acase-report was associated with significant reduction of time
spent on line23. The beneficial effect persisted even after patients were randomized to
drug or placebo group. Bupropion, used among patients with gaming addiction with or
without depression, resulted in considerable degree of reduction in craving and time
spent on gaming. This improvement was not associated with any change in
depression.24 Neuroimaging studies on brain activity of patients treated with Bupropion
(left dorsolateral prefrontal cortex, left occipital lobe) did not differ from that of healthy
control.25, 26
3.2.2. Stimulants
In view of the high comorbidity of ADHD i.e. 30-50% with IA, methylphenidate has
been used for ADHD children addicted to video gaming. Methylphenidateinthe dose
range of 18-54 mg/day used among sixty two drug naïve children showed significant
benefit on both IA scale, ADHD rating score and Visual continuous performance test
(CPT)12
Other drugs like memantine, a glutamate agonist, naltrexone, an opioid antagonist,

mood stabilizers, atypical antipsychotics have been tried without much benefit.27
4. PSYCHOLOGICAL VERSUS PHARMACOLOGICAL
Winkler et al. in a recent meta-analysis of sixteen methodologically sound studies
reported that there is no significant difference in the efficacy of improvement between
both the interventions with regard to outcome parameters like time spent online,
depression and anxiety. The effect sizes for psychological treatment (95%CI: 1.22-2.33)
and pharmacological treatment (95% CI: 0.28-2.23) were similar. At the same time
there are only three methodologically sound studies on pharmacological treatment.22
Key Recommendations
(based on limited number of studies n=16 and meta-analysis)22,27
Psychological
Cognitive Behaviour Therapy for Internet Addiction is useful in reducing time spent
online, recovery from depression (A)
Other psychological therapies that include individual CBT along with family
therapy or group therapy etc. are also effective (B)
Individual therapy is better in the initial part of intervention compared to group
therapy. (C )
The short term gains achieved in the therapy are maintained over long period
(almost upto a year) (B)
Pharmacological (based on three studies)
Preliminary evidence shows that Pharmacological treatments alone (Escitalopram,
Bupropion, Methylphenidate) are effective in short term (C ).
Lack of robust and methodologically sound studies focusing on IA.
Others
Combination of these two therapies may be recommended presently as the most
effective intervention approach
In view of high comorbidity, effective therapy requires individual approach and
must be adjusted according to the patient's needs
5. CONCLUSION
In summary, the validity of Internet Addiction as a separate diagnostic entity still
remains to be established. Nevertheless, pathological use of the Internet is a problem
that is increasingly brought to the attention of the clinician. The assessment includes
assessment of the time spent on Internet-related activities, the kind of Internet activity,

the motivating factors for pathological use of the Internet, consequent disruption to
functioning and health, presence of co-morbidity and an assessment of temperament.
Engagement in treatment can pose a challenge, particularly when the individual's
occupation is Internet-based. Management includes a combination of psychological
interventions and appropriate pharmacotherapy.
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games: A comparative study of hyperactive and control children. Eur
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webâ€”harmful use of the Internet and its correlates. Eur Psychiatry.
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OTHER PUTATIVE BEHAVIOURAL ADDICTIONS
Arun Kandasamy
Lekhansh Shukla
On behalf of
2016
Other Putative Behavioural Addictions
CONTENTS
Executive Summary
1. Introduction
1.1 Current understanding and principles
1.2 Epidemiology – Global and Indian scenario
1.3 Consequence and disease burden
1.4 Syndromes under study
1.5 Comorbidity and related considerations
2. Scope and methodology of guidelines

2.2 Scope of guidelines
2.3 Limitations
3. Food addiction
3.1 Introduction and current understanding
3.2 Assessment
3.3 Pharmacological management – evidence and recommendation
3.4 Non-pharmacological interventions – evidence and recommendation
4. Sex addiction
4.1 Introduction and Current understanding
4.2 Diagnostic criteria
4.3 Assessment
4.6 Ethical and legal concerns
5. Compulsive buying disorder

5.2 Assessment

6. Exercise addiction
6.2 Assessment
6.3 Management
7. Conclusion

EXECUTIVE SUMMARY
Introduction: Behavioural addiction is an emerging field. There are certain similarities
between substance use disorder and behavioural addictions. Components model of
addictions suggest that any behavioural excess should be evaluated on six parameters;
salience, mood modification, tolerance, withdrawal symptoms, conflict and relapse.
Existence and prevalence of these disorders in Indian population require further studies.
Food addiction, sex addiction and compulsive buying are backed by prevalence studies
while other proposed behavioural addictions have only case reports/case series as
evidence. There is high comorbidity with mood, substance use disorders and
temperamental traits of externalizing or internalizing spectrum.
Scope and Methodology of Guidelines: A literature search of PubMed and Google
Scholar database was done, references of review articles and monographs were also
included. These guidelines are meant to support clinicians and are limited by the
scarcity of evidence available in this field.
Food addiction: Repeated binges of hyper-palatable (high fat or sugars) foods, loss of
control, negative affective states are features suggestive of food addiction. There are no
instruments which can be suggested for routine use in Indian population. Treatment of
comorbidities is strongly recommended. Combination of psychological and
pharmacological therapy is essential. Fluoxetine or Topiramate can be chosen as first
line agents along with cognitive behaviour therapy. Lifestyle modification and dietary
counselling should be provided in all cases of food addiction and/or obesity.
Sex addiction: Non-paraphilic compulsive sexual activity with features of loss of
control, tolerance, withdrawal symptoms and relapses is conceptualized as sex
addiction. PATHOS is a brief screening instrument that can be used in routine clinical
care. Treatment of comorbid mood disorder, Attention deficit hyperactive disorder
(ADHD) is recommended. Fluoxetine or Sertraline can be used as first line agents
however, evidence is not strong. Similarly, there is lack of evidence for psychotherapy
models.
Compulsive buying disorder: Irrepressible, uncontrolled excessive buying that
continues despite negative consequences is suggested as hallmark of compulsive
buying disorder. Evaluation and treatment of comorbid disorders is strongly indicated.
There is insufficient evidence to recommend any pharmacotherapy. Cognitive
behavioural therapy has shown promising improvement and is recommended as a first
line intervention.
Exercise addiction: Excessive exercise with features of salience, withdrawal, loss of
control and tolerance is proposed as exercise addiction. It should be differentiated from
eating disorders (anorexia nervosa, bulimia nervosa) and body dysmorhophobia. There
is insufficient evidence to recommend any pharmacological or non-pharmacological
treatment.

1. INTRODUCTION
1.1 Current understanding and principles
The area of behavioural addictions is an evolving field. This chapter will address
syndromes that are less established than pathological gambling and Internet use
disorder but need mention due to emerging evidence. It is emphasized that every
'behavioural excess' is not conceptualized as an addiction. Mark Griffith's components
model of addiction gives the most studied and convergent set of criteria for diagnosing
behavioural addiction. It consists of six core components: salience, mood modification,
tolerance, withdrawal symptoms, conflict, and relapse (Panel1). It should be noted that
some of the syndromes discussed in this chapter are included in official classifications
with a different name while some are not included in any official classification currently.
PANEL 1 - COMPONENTS MODEL OF BEHAVIOURAL ADDICTION

Salience - behaviour becomes the most important activity in a person's life and tends
to dominate his or her thinking, feelings, and behaviour.
Mood modification - the emotional effect the behaviour has on the individual which
often serves as a coping strategy and is reported as the arousing “rush” or the
numbing or the tranquilizing “escape” the behaviour provides.
Tolerance - process whereby increasing amounts of the behaviour are required to
achieve the former mood-modifying effects, often meaning greater periods of time
are spent engaging in the behaviour, and/or there is a desired escalation in the
intensity, recklessness, destructiveness, and ego-dystonic nature of the behaviour.
Withdrawal symptoms - unpleasant feeling states and/or physical effects (e.g., the
shakes, moodiness, irritability) that occur when the person is unable to engage in the
behaviour.
Conflict – discord between the person and those around him or her (i.e.,
interpersonal conflict), conflicts with other activities (i.e., social life, work, hobbies,
and interests) or from within the individual him- or herself (i.e., intrapsychic conflict
and/or subjective feelings of loss of control) that are concerned with spending too
much time engaging in the addictive behaviour.
Relapse - tendency for repeated reversions to earlier patterns of excessive behaviour
to recur and for a common return to the most extreme patterns of excessive
behaviour soon after periods of control.
1.2 Epidemiology – Global and Indian scenario.

There is a dearth of epidemiological studies and it is premature to speculate on
prevalence rates. A review shows prevalence of food addiction (2%), love addiction

(3%), sex addiction (3%), exercise-addiction (3%), work addiction (10%) and shopping
addiction (6%) in US population.1 A longitudinal study reports similar one year
prevalence rates where eleven percent responders reported 'at least one excessive
behaviour'. Specifically, food addiction (7.4%), shopping addiction (4.5%), sex
addiction (2.5%) and exercise addiction (3.3%) were identified through self-diagnosis.2
In India, an ICMR funded survey identified food addiction (1.6%; 2% male & 1.2%
female), Shopping addiction (4%; male-3.2% & female-4.8%), Sex addiction (2%; 0.3%
male&0.1% female) and Exercise addiction (5.6%; 7.5% males & 3.8% females).3
1.3 Consequence and Disease Burden
Since these syndromes are relatively recent concepts they do not lend themselves to
traditional estimates of morbidity and mortality. However, they indirectly contribute to
significant disease burden globally. For example, there is a link between obesity and
food addiction. Obesity accounts for 3·4 million deaths, 3·9% of years of life lost, and
3·8% of disability-adjusted life-years (DALYs) worldwide.4 Further research is needed to
quantify disease burden due to other behavioural addictions.
1.4 Syndromes under study
Since behavioural addiction is an evolving concept there are a number of excess
behaviours that are being conceptualized in this rubric. It's noted that while some of
these syndromes have other names in official classifications, most are not diagnosable
using DSM-5 or ICD-10. It is necessary to view these conditions in perspective of
available evidence and there place in diagnostic systems. A list of these conditions
along with the literature supporting them and their relationship with existing diagnoses
is presented in Table 1.
Table 1 : List of proposed behavioural addictions
Behavioural Proposed Evidence Related DSM5 Related ICD10
Excess 'Addiction' Diagnoses Diagnoses
Food Consumption Food addiction Self-report surveys. Feeding and Eating Atypical Bulimia
Prevalence and disorders. Nervosa.
follow up studies. Binge eating Other eating
(Convenient disorder. disorder.
samples)
Sexual activities Sex addiction Self-report surveys. Nil Excessive sexual
Prevalence and drive.
follow up studies.
(Convenient
samples)
Shopping and Compulsive Self-report and Nil Other habit and
spending. buying/ Shopping prevalence studies. Impulse disorders.
addiction (Convenient
samples)

Behavioural Proposed Evidence Related DSM5 Related ICD10

Excess 'Addiction' Diagnoses Diagnoses
Exercise. Exercise addiction. Self-report surveys. Nil Nil
Work/Occupationa Work addiction. Self-report surveys. Nil Nil
l activities
Tanning Indoor tanning Case reports. Nil Nil
addiction.
Romantic Pursuits Love addiction Theoretical Nil Nil
Postulates.
1.5 Comorbidity and related considerations

There is a high comorbidity of substance use disorders and other mental disorders in this
group of patients. Specifically affective disorders, attention deficit hyperactivity
disorder and anxiety disorders are commonly reported. In addition temperamental
factors like externalizing or internalizing temperaments are more common in this
population. Finally, behavioural addictions can co-exist and often interact with each
other which has been called addiction interaction disorder.5 Thus it is essential to take a
detailed history, perform toxicology screening and rule out other conditions.
2. SCOPE AND METHODOLOGY OF GUIDELINES
Relevant literature was identified through a PubMed literature search for publications
related to this guideline. Searches were conducted using two sets of keywords. First a
literature search was conducted using “Behavioural addictions OR Process addictions
OR Impulsive compulsive disorders”. This was followed by specific search terms
namely: “Food addiction OR eating addiction”, “Shopping addiction OR compulsive
buying”, “Sex addiction OR sex dependency OR excessive sexual drive OR
nymphomania OR satyriasis” and “Tanning addiction”. Results were filtered with
language- English, species-human and availability-abstract. Additionally bibliographic
references of review articles and monographs were reviewed.
2.2 Scope of guidelines
These guidelines are neither comprehensive nor definitive. Psychiatrists caring for
patients should consider the evidence base but not be limited by the recommendations
made here. Further these guidelines are limited by the scarce scientific evidence
available in this field. It's an emerging field riddled with controversies thus guidelines
will require revision as new evidence appears.
3. FOOD ADDICTION
3.1 Introduction and Current understanding.
A recent conceptualization of obesity (due to excessive calorie consumption) and

inability to alter this behaviour is that hyper-palatable foods are addictive.6 This concept
is more pertinent for patients with binge eating and clear loss of control regarding
certain calorie dense hyper-palatable food items (high fat, high sugar foods).7 There are
two important caveats to this conceptualization. Firstly, obesity is not always due to
disordered eating, other endocrine causes should be ruled out. Secondly, overeating
itself does not indicate an addictive process, for many individuals it is due to large
potions, liberal snacking and poor food choices.8
3.2 Assessment
3.2.1 Brief Overview
First Assessment is an opportunity of establishing rapport and further engagement
which is required for a more nuanced understanding of patient'sproblems. There can be
different contexts in which patient presents for example; referral by a physician or
specialist, pre-bariatric surgery referral, self-referral or being brought by family for
'disordered eating'. A final formulation may not be reached till a number of interviews
are conducted. This should be communicated to patient and family.
3.2.2 Clinical History
A detailed history should include; purpose and context of current visit, comorbid
psychiatric or physical disorders, current medications if any, substance use history,
history of other behavioural addictions, premorbid personality and temperament.
Family history of substance use disorders, obesity, metabolic disorders and current
living arrangement is important. Important findings that demand a more detailed
evaluation for food addiction, based on available literature are highlighted in Panel2.
There are certain differential diagnoses that should be considered and are highlighted in
Panel3. It should be kept in mind that Binge eating disorder and Food addiction are
competing formulations and cannot be delineated at present.9
PANEL 2 - FEATURES SUGGESTING FOOD ADDICTION

1. Recurrent Binge eating episodes: Bouts of unusually large food intake in
relatively short periods of time.
2. Periodic poor control: increased binges after periods of relative deprivation.
3. Loss of control: diminished ability or willingness to cut down food consumption.
4. Hyper-palatable foods: high fat and high sugar foods.
5. Higher negative affect and emotional dysregulation.

PANEL 3 - DIFFERENTIAL DIAGNOSIS OF FOOD ADDICTION

1. Other eating disorders: presence of purging, compensation and body image
disturbance.
2. Atypical depression: presence of hypersomnia and depressive symptoms.'
3. ‘Comfort foods': lack of multiple binges, clear stressors.
4. Adonis complex/muscle dysmorphia: body-image disturbances, high protein
foods.
5. Drug induced hyper-phagia: atypical anti-psychotics, cyproheptidine,
cannabinoids, and steroids.
6. Endocrine disorders: thyrotoxicosis, recurrent hypoglycaemia due to
medications or brittle diabetes.
7. Neurological disorders: Kleine Levin syndrome.
8. Rare genetic syndromes: Prader-Willi syndrome and Bardet Biedl Syndrome.
3.2.3 Physical examination

A thorough physical examination specially focusing on body mass index, waist to hip
ratio, acanthosis nigricans, stigmata of substance use disorders, blood pressure,
peripheral pulses and circulation, stigmata of purging or repeated vomiting (erosion of
enamel, callosities on knuckles) and stigmata of endocrine illnesses (skin changes,
tachycardia, moon facies) should be done. Body weight and waist to hip ratio can be
used during the course of treatment to monitor improvement and enhance motivation.
3.2.4 Instruments
Yale Food addiction scale (YFAS) developed by Gearhardt, Corbin, & Brownell in 2009
is the most widely used instrument for food addiction.10 However this has not been
validated in Indian population. Since the scale involves culturally determined items
(name of food items with high fat and sugar content for example Pretzel, Bacon) it may
not hold valid in Indian scenario. It is not recommended for routine clinical use.
3.2.5 Investigations
If the psychiatrist is the first point of contact and referral to physician is not planned, a
number of investigations are advised to rule out metabolic syndrome. Fasting and post
prandial blood sugar, fasting lipid profile, haemogram, renal function tests and hepatic
function tests should be reviewed. If hepatic functions are deranged in absence of
alcohol use abdominal ultrasound should be done to evaluate non-alcoholic steatotic
hepatitis (NASH). A toxicology screen can be used depending on index of suspicion.
Similarly, sexually transmitted infections should be ruled out if there is a history of high
risk sexual encounters. In females, Polycystic ovary disease may be a pre-existing or

comorbid condition and mid-cycle follicle stimulating hormone (FSH), Luteinizing

hormone (LH), Testosterone and sex hormone binding globulin (SHBG) can be done
before referral to an endocrinologist.
3.3 Pharmacological Management- evidence and recommendations.
Identification and treatment of comorbid conditions – ADHD, depression and anxiety
disorders is recommended. There are no well-studied pharmacotherapies for food
addiction as it is not a recognized diagnosis. Pharmacotherapy for binge eating disorder
and obesity are worth reviewing in this context – Table 2. In summary anti-depressants
(SSRI and SNRI) decrease frequency of binges in short term, anti-epileptic medications
decrease both the frequency of binges and promote weight loss while anti-obesity drugs
only promote weight loss.11,12 There are a number of drugs and combinations that are in
various phases of development and may be available shortly. They are summarized in
Panel 4.
Table 2: Pharmacotherapy for binge eating disorder and anti-obesity drugs
Pharmacological Dose Evidence Strength of Expected Common side effects

agent(s) recommendation Improvement
Fluoxetine 20 to 60 1B A Decreased frequency Gastrointestinal
mg per of binges. discomfort.
day.
Sertraline 50 to 1B A Decreased frequency Gastrointestinal
200 mg of binges. discomfort.
Fluvoxamine 50 to 1B A Decreased frequency Anticholinergic
300 mg of binges. symptoms.
Discontinuation
syndrome.
Citalopram 20 to 1B A Decreased frequency Gastrointestinal
60 mg of binges. symptoms.
Topiramate 25 to 1A A Decreased binges and Cognitive deficits.
300 mg weight loss.
Atomoxetine 10 to 1B A Decreased binges. Gastrointestinal
80 mg symptoms.
Orlistat 60 to 1A A Weight loss through Steatorrhea and
360 mg decreased fat vitamin deficiencies.
absorption.
Metformin 500 mg 2A B Weight loss. Gastrointestinal
to symptoms.
2000mg

PANEL 4 - EMERGING ANTI-OBESITY TREATMENTS

1. Lorcaserin: 5HT2C agonism, satiety promoting agent. Dose: 10mg twice a day.
Significant interaction with anti-depressants.
2. Fixed dose Combination of Phentermine and Topiramate:3.75 mg
phentermine/23 mg topiramate to 7.5 mg/46 mg combination.
3. Fixed dose combination of Bupropion and Naltrexone.
4. Fixed dose combination of Bupropion and zonisamide.
5. Tesofensine: tri-monoamine reuptake inhibitor, inhibits reuptake of serotonin,
nor-epinephrine and dopamine.
3.4 Non-pharmacological interventions – evidence and recommendation.

3.4.1 Overview
Pharmacological treatment has modest and short-lasting benefit. Current expert opinion
is that a combination of pharmacotherapy and psychotherapy is optimal management
strategy.13 Similar to pharmacological management, there is an absence of literature
pertaining to psychotherapy of food addiction per se. However, there is extensive
literature on psychotherapy of binge eating disorder which will be reviewed. Summary
of evidence for psychotherapeutic interventions is presented in Panel 5. Major
modalities and recommendations are summarized in Table 3.
Table 3 : Psychotherapeutic interventions in food addiction
Psychotherapeutic Category of evidence Strength of recommendation

intervention
Lifestyle and Dietary counselling 1A A
Cognitive Behaviour therapy 1B A
Interpersonal Therapy 1B A
Dialectical Behaviour Therapy 1C A
Self Help 4 D
Peer Support 4 D
3.4.2 Lifestyle modification and dietary modification

Following assessment a counselling session focusing on dietary habits, physical activity,
and behaviour modification must be offered to all clients. (Strength of recommendation:
S). Involving a dietician or general physician for comprehensive care can be considered
based on resources, severity of obesity and presence of comorbidities like vascular
disease, diabetes or hypertension. Obesity is a disease of energy imbalance, counselling
should address energy consumption (diet), energy expenditure (physical activity), and
how to incorporate this information into daily lives (behaviour therapy). Lifestyle
management has been shown to result in a modest (typically 3–5 kg) weight loss
compared with no treatment or usual care.14
PANEL 5 - FOOD ADDICTION PSYCHOTHERAPY- SALIENT POINTS

Types of interventions: Lifestyle and dietary modification, CBT, DBT, IPT, peer
support (Overeaters anonymous) and self-help.
l Any intervention is better that no-intervention.
l CBT/DBT/IPT have comparable efficacy in reducing binges in short term.
l Minimal effect on body weight with any psychotherapeutic intervention.
l CBT and DBT can be given in individual or group format.
3.4.3 Cognitive behavioural therapy (CBT)

No CBT program for food addiction currently exists, although CBT is a relatively well-
established psychological treatment for BED.15 CBT for BED consists of three stages
spanning approximately 20 sessions. Stage one consists of establishing a therapeutic
relationship and on educating the patient on the rationale underlying the CBT approach.
Stage two emphasizes replacing binge eating with a regular pattern of eating and
address cognitive distortions including dichotomous reasoning, low self-esteem, and
extreme perfectionism. The third stage ensures that progress is maintained it also
includes formulating relapse plans.
3.4.4 Dialectical Behavioural therapy (DBT)
DBT proposes that individuals who struggle with BED may lack the skills necessary to
cope with their affective states and, therefore, may use food as a means to avoid or
escape from emotional distress. DBT for BED (DBT-BED involves the following
modules: mindfulness skills, emotional regulation, and distress tolerance. DBT-BED is
effective at enhancing patients' overall level of emotional regulation and may be
superior to CBT in terms of abstinence from binge eating.16
3.4.5 Interpersonal Therapy (IPT)
IPT typically focuses on the connection between current symptoms and interpersonal
(i.e., relationship) problems and holds the assumption that the condition is maintained
by interpersonal problems. IPT may be comparable to CBT in reducing binges and
better in maintaining improvement.17
3.4.6 Self-help
For milder cases a manualized CBT format administered in a guided or purely self-help
format may be useful.18 Considering that it does not demand many resources it is a
feasible first step towards therapy.

3.4.7 Peer support

12 step programs like overeaters-anonymous may be beneficial for some patients.
Systematic evidence of efficacy is lacking currently.19
FOOD ADDICTION
Key Features: Repeated binges, loss of control, consumption of hyper-palatable
l
foods, and relapses.

Overlaps with: Binge eating disorder.
l
Comorbidities: Mood disorders, anxiety disorders, substance use disorders, other

l
behavioural addictions, ADHD.

Always recommended: Treatment of comorbidities, lifestyle and nutritional
l
counselling, follow-up and weight monitoring.

Recommended: Fluoxetine 20-60mg/day OR Topiramate 25-200mg/day AND
l
Cognitive behavioural therapy.

Can be considered: Sertraline 50-200mg/day, Zonisamide 100-600mg/day,
l
Atomoxetine 25-60mg/day anti-obesity drugs, Interpersonal therapy, dialectical

behavioural therapy.
Treatment Goals: control of binges in short term, sustained weight loss in long
l
term.
4. SEX ADDICTION
4.1 Introduction and current understanding.
Excessive, compulsive sexual desire and activities have been variously named as – sex
addiction, compulsive sexual behaviour, sex dependency and impulsive-compulsive
sexual disorder. Despite being reported and postulated since 1812 by Benjamin Rush it
was not included in DSM 5 due to lack of adequate evidence.20 Current
conceptualization of sex addiction is a non-paraphilic excessive sexual behaviours with
features of impulsivity, compulsivity and causing significant personal distress, social or
medical comorbidity. This conceptualization and resultant criteria has high internal
consistency, inter-rater reliability and cross-validity with measures of hyper-sexuality,
impulsivity, stress-proneness and emotional dysregulation.21
4.2 Diagnostic criteria
There are multiple sets of criteria proposed by different groups working in the field.
There is a significant similarity between these criteria and criteria for substance use
disorders. Criteria proposed by Carnes et al is mentioned in Panel6 as it has been
studied most extensively and has longitudinal stability.22
PANEL 6 - SEXUAL ADDICTION DIAGNOSTIC CRITERIA

A. A minimum of three criteria met during a 12-month period:
1) Recurrent failure to resist impulses to engage in specific sexual behaviour.
2) Frequent engaging in these behaviours to a greater extent or longer duration
than intended.
3) Persistent desire or unsuccessful efforts to stop, to reduce, or to control
behaviours.
4) Inordinate amount of time spent in obtaining sex, being sexual, or
recovering from sexual experiences.
5) Preoccupation with the behaviour or preparatory activities.
6) Frequently engaging in the behaviour when expected to fulfil occupational,
academic, domestic, or social obligations.
7) Continuation of the behaviour despite knowledge of having a persistent or
recurrent social, financial, psychological, or physical problem that is caused
or exacerbated by the behaviour.
8) Need to increase intensity, frequency, number, or risk of behaviours to
achieve the desired effect or diminished effect with continued behaviours at
the same level of intensity, frequency, number, or risk.
9) Giving up or limiting social, occupational, or recreational activities.
10) Distress, anxiety, restlessness, or irritability if unable to engage in the
behaviours.
B. Has significant personal and social consequences (such as loss of partner,
occupation, or legal implications).
4.3 Assessment
4.3.1 Brief overview
There are multiple considerations during assessment like – context of assessment,
confidentiality, privacy, legal implications and need to remain non-judgmental.
Context of assessment can be self-referral, marital conflict, under duress or for other
psychiatric problems. Multiple interviews may be required to establish adequate
comfort level.
4.3.2 Clinical History
Clinical history should focus on detailed sexual and relationship history, fantasies,
internal conflict and compulsivity. A clear understanding of gender identity, sexual
orientation and sexual preferences is necessary to avoid misdiagnosis. A frank
discussion regarding sexual preferences and conflicts with law is required.

Externalizing temperamental traits of impulsivity, emotional dysregulation are

frequently present. Comorbidity of substance use disorders, attention deficit
hyperactivity disorder and mood disorder is also common. A medical history focusing
on symptoms of sexually transmitted infections should be collected. Finally if patient is
in a long term relationship, relationship problems should be looked for. Differential
diagnoses for sexual addiction are mentioned in Panel 7 and should be ruled out.
PANEL 7 - DIFFERENTIAL DIAGNOSIS OF SEXUAL ADDICTION

1. Paraphilias: Deviant sexual preference is the primary complaint. Paraphilic
tendencies can be present in sexual addiction also but they are not the primary
symptom.
2. Affective disorders: hypomania, mania and rarely atypical depression can be
accompanied by hyper-sexuality but it is characteristically episodic and
accompanied by other symptoms.
3. Substance use disorders: stimulant, anabolic steroids and other substance abuse
can be accompanied by periods of excessive sexual activity.
4. Mental retardation: lack of inhibition and ability to modulate impulses.
5. Dementia: hyper-sexuality can be seen in fronto-temporal degeneration.
6. Neurological damage due to various causes like head injury, multiple sclerosis.
7. Endocrine: hyper-testosteronism due to tumour.
8. Drug induced: testosterone supplementation, GnRH analogues, levodopa and
dopamine agonists.
9. Rare genetic disorders: Kleine Levin syndrome.
4.3.3 Physical examination

Special focus should be given to genital examination and stigmata of substance use
disorder.
4.3.4 Investigations
Important investigations in addition to routine are serology for sexually transmitted
infections, toxicology screen and in atypical cases a sex hormone profile (serum FSH,
LH, free testosterone and sex hormone binding globulin).
4.3.5 Instruments
Sexual addiction screening test – revised (SAST-R) has 20 core items and 25 subscale
items. It is valid in homosexual patients and has a good reliability at a cut-off of 6.23
However it has a total of 45 items and is time consuming. Recently, a screening
instrument called PATHOS was developed to aid in the identification of those who may

have sexual addiction. Similar to the CAGE, this mnemonic six- item screener (extracted
from the SAST-R) was found to have acceptable internal consistency (0.94–0.77) and
using the cut-off score of 3, demonstrated good sensitivity and specificity ratings.24 See
Panel 8 for a list of PATHOS items.
PANEL 8 - PATHOS ITEMS

1. Do you often find yourself preoccupied with sexual thoughts? (Preoccupied)
2. Do you hide some of your sexual behaviour from others? (Ashamed)
3. Have you ever sought help for sexual behaviour you did not like? (Treatment)
4. Has anyone been hurt emotionally because of your sexual behaviour? (Hurt)
5. Do you feel controlled by you sexual desire? (Out of control)
6. When you have sex, do you feel depressed afterwards? (Sad)
A positive response to more than 3 questions indicate need for further assessment.
4.4 Pharmacological management - evidence and recommendation.

Pharmacological management should be a component of multi-faceted plan including
individual psychotherapy and marital therapy. Most importantly if a comorbidity like
ADHD or mood disorder is identified it should be treated in earnest. Evidence for
treatment of sexual addictions (conceptualized as non-paraphilic sexual compulsivity)
is sparse. Pharmacotherapy aimed at reducing libido has much evidence in paraphilias
and sex-offenders24-26; however this evidence cannot be extrapolated to sex addiction.
Treatment of sex addiction aims to improve control over sexual desire rather than
complete suppression of it. A summary of pharmacological agents and evidence
supporting their use is summarized in Table 6.
Table 6 : Pharmacotherapy for sex-addiction
Pharmacological Dose Evidence Strength of Disorder studied Common side effects
agent(s) recommendation
Fluoxetine27 20 to 80 2B B Paraphilias and Gastrointestinal
mg per non-paraphilic hyper discomfort.
day sexuality
Sertraline 50 to 2B B Paraphilias Gastrointestinal
200 mg discomfort.
Naltrexone28 100 mg 3 C Non-paraphilic hyper Fatigue, anhedonia
sexuality
4.5 Non Pharmacological interventions – evidence and recommendation.

Components of non-pharmacological management as described by Carnes et al22 are

summarized in Panel 9. It is noted that there is a lack of controlled comparative data.

(Category of evidence – 4, strength of recommendation- D).
4.6 Ethical and legal concerns
Hyper-sexuality can lead to conflict with law. However, it is neither necessary nor
sufficient for diagnosis. A discussion with patient regarding legal implications of his/her
behaviour should be undertaken and recorded. Clinicians are advised to be mindful of
potential medico-legal issues and ethical dilemmas when dealing with sexual
addiction. A potential scenario could be about disclosure to spouse during therapy
sessions. Some legal statutes may require obligatory reporting of ongoing sexual abuse
like 'The Protection of Children from Sexual Offences Act, 2012'.29
PANEL 9 - PSYCHOSOCIAL INTERVENTION FOR SEXUAL ADDICTION

PHASE I - INTERVENTION
l Survey extent of problematic behaviour
l Teach about illness
l Referral to 12-Step Program
l Confront denial
l Agree on behaviour contract
PHASE II- INITIAL TREATMENT
l 12-Step attendance
l Complete first step of 12-step process
l Agree on writing an abstinence definition
l Written relapse-prevention plan
l Complete period of celibacy
l Develop a sex plan
l Partner and family involvement
l Multiple addiction assessment
l Trauma assessment
l Group therapy
l Shame reduction
PHASE III- EXTENDED THERAPY
l Complete steps 2 – 4 of 12-step process
l Developmental issues
l Family-of-origin issues
l Grief resolution
l Marital and family therapy
l Career issues
l Trauma therapy

SEX ADDICTION
Key Features: Failure to resist impulses, desire to control or stop, increasing time
l
spent, continued despite adverse consequences.

Overlaps with: Disorders of sexual preference.
l
Comorbidities: Substance use disorders, ADHD.

l
Always recommended: Treatment of comorbidities, engagement in long term

l
therapy.
Recommended: Fluoxetine 20-60mg/day.
l
Can be considered: Augmentation with Naltrexone 100-200mg/day.

l
Treatment Goals: Control of high risk contacts and commitment to long term
l
therapy.
5. COMPULSIVE BUYING DISORDER (CBD)

Compulsive buying disorder or shopping addiction has been variously conceptualized
as impulse control disorders, obsessive-compulsive and related disorders, behavioral
and substance addictions, and mood disorders.30 Most of the epidemiological data is
from western and high income group countries.31
5.2 Assessment
A focused assessment to evaluate 'excessive buying' is required prior to diagnosing
CBD. Current conceptualization and diagnostic features of CBD are summarized in
Panel10. Temperamental traits of impulsivity, distractibility and cognitive schemas
which place high value on materialism are considered to be risk factors.32 Comorbidity
of mood disorder, anxiety disorders, substance use disorders and other behavioural
addictions should also be evaluated. Differential diagnoses to be considered are
summarized in Panel 11.
5.3 Pharmacological management - evidence and recommendation
Treatment of comorbid mood disorder, attention deficit hyperactivity disorder should
be optimized. There is insufficient evidence to recommend pharmacotherapy in
patients with no comorbidities. In a study comparing Tab Fluvoxamine 300mg and
placebo there was no difference in response.33
5.4 Non-Pharmacological interventions – evidence and recommendation
Cognitive behavioural therapy (CBT) focusing on actual shopping behaviour problems,
financial management, emotions and feelings associated with buying behaviour, self-
esteem and consequences has shown preliminary improvement in two studies.34,35

Group therapy and individual psychodynamic therapy has also been proposed but with
no efficacy data for comparison. Thus CBT is recommended as a treatment for
compulsive buying disorder. (Evidence category 1B, strength of recommendation A).
PANEL 10 - FEATURES SUGGESTING COMPULSIVE BUYING DISORDER

1. Irrepressible Buying: individual must be engrossed in shopping in a compulsive
way. He or she will spend hours shopping and spending each week, and the
shopping activity is coupled with an intense urge to purchase one or multiple
items. This unavoidable urge to shop and purchase is overpowering and
irrepressible, and is precisely what leads to uncontrollable shopping behaviours.
2. Uncontrollable Buying: most individuals with CBD have overwhelming urges
to buy products, and it is nearly impossible for individuals to successfully resist
these urges.
3. Negative Consequences of Buying: most individuals fail to change this
behaviour despite negative consequences in all different domains of individuals'
lives, including financial, familial and occupational.
PANEL 11 - DIFFERENTIAL DIAGNOSIS OF EXCESSIVE SHOPPING

1. Affective disorders: hypomanic or manic episodes, clearly episodic with
accompanying symptoms.
2. Hoarding disorder: presence of clutter and poor insight.
3. Obsessive compulsive disorder: obsessions/magical thinking/need for
completion or just right phenomenon.
4. Dementia: Diogenes syndrome
6. EXERCISE ADDICTION
6.1 Introduction and current understanding.
Exercise addiction has been variously referred to as compulsive exercise, obligatory
exercise or exercise abuse. Initially believed to be a 'positive addiction'33 it is
increasingly realized that some individuals have patterns of exercise that are
dysfunctional.34 It remains a rare condition but is more common in individuals related to
professional sports. In such cases it is difficult to delineate it from high levels of
commitment and competitiveness. Further, there is substantial debate if this entity exists
separate from eating disorders.35
6.2 Assessment
Excessive exercise should be evaluated keeping in mind the components model of

addiction. An important distinction should be made between primary exercise

addiction where exercise itself is the objective and other disorders like eating disorders,
muscle dysmorphia where objectives are different. A history of anabolic steroid abuse,
repeated overuse injuries, disruption of social and familial ties is important.
6.3 Management
There is insufficient evidence to recommend pharmacological or non-pharmacological
management. It is proposed that approaches like CBT which are effective for eating
disorders may be effective in exercise addiction.
7. CONCLUSION
Almost all the pathological behaviours named above do not have enough evidence to
get into the mainstream diagnostic criteria as of now. There is also a lack of evidence
towards a standard protocol of management. But the clinicians come across such cases
regularly. In view of these facts, the authors are of the opinion that:
1. A detailed assessment of the behaviour under investigation along with assessment
of comorbid psychiatric and medical disorders and the temperament will be useful
to arrive at the focus of management in these disorders.
2. Management should include an individualized treatment plan which would
comprise of rapport building, motivational intervention, management of
temperamental issues and comorbidities along with management of the problem
behaviour. The role of pharmacotherapy other than treating co-morbidities still
needs to be established.
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addictions: a 5-year longitudinal study. BMC Psychiatry. 2015;15:4.
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7. Gearhardt AN, White MA, Masheb RM, Morgan PT, Crosby RD, Grilo CM. An
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8. Moreno C, Tandon R. Should overeating and obesity be classified as an addictive
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a Racially Diverse Sample of Obese Patients with Binge Eating Disorder in Primary Care
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10. Gearhardt AN, Corbin WR, Brownell KD. Preliminary validation of the Yale Food
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11. Reas DL, Grilo CM. Review and Meta-analysis of Pharmacotherapy for Binge-eating
Disorder. Obesity. 2008;16(9):10.1038/oby.2008.333.
12. Reas DL, Grilo CM. Current and Emerging Drug Treatments for Binge Eating Disorder.
Expert Opin Emerg Drugs. 2014;19(1):99-142.
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14. Wadden TA, Butryn ML, Wilson C. Lifestyle modification for the management of
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Database Syst Rev. 2003(1):Cd000562.
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term efficacy of psychological treatments for binge eating disorder. Br J Psychiatry.
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Consult Clin Psychol. 2000;68(4):564-72.
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24. Carnes PJ, Green BA, Merlo LJ, Polles A, Carnes S, Gold MS. PATHOS: A brief screening
application for assessing sexual addiction. J Addict Med. 2012;6(1):29-34.
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Disord. 2002;10(1):49-60.

SECTION D :
DUAL DIAGNOSIS
DUAL DIAGNOSIS :
PSYCHOTIC DISORDERS
Yatan Pal Singh Balhara

Sathya Prakash
Ananya Mahapatra
Siddharth Sarkar
On behalf of
2016
Dual Diagnosis : Psychotic Disorders
CONTENTS
Executive Summary
1. Introduction
1.1. Concept of dual diagnosis
1.2. Epidemiology of dual diagnosis: psychotic disorders
1.3. Importance of dual diagnosis: psychotic disorders
2.1. Overview of the guidelines
2.2. Scope of the guidelines
2.2.1. Psychotic dual diagnosis
2.3. Methodology of guideline development
3. Assessment and formulation
3.1. General issues
3.2. Treatment aims / goals
3.3. Deciding treatment setting
3.4. Assessment of dual diagnosis: psychotic disorders
3.4.1. General overview
3.4.2. Clinical history
3.4.3. Physical examination
3.4.4. Assessing risk
3.4.4.1. Violence
3.4.4.2. Suicidality
3.4.5. Rating scales
3.4.6. Investigations
3.5. Recommendations for practice
4. Interventions in psychotic dual diagnosis
4.1. Motivation enhancement intervention
4.2. Pharmacological measures
4.2.1. For substance use disorder
4.2.1.1. Short term management
4.2.1.1.1. Interaction of anti-psychotic medications
with substance of abuse and medicines
used for its short term management
(management of withdrawals)

4.2.1.2. Long term management

4.2.1.2.1. For alcohol use disorders
4.2.1.2.2. For opioid use disorders
4.2.1.2.3. For tobacco use disorders
4.2.1.2.4. For cocaine and other stimulant use disorders
4.2.1.2.5. For cannabis use disorders
4.2.2. For psychotic disorder
4.2.2.1. First generation anti-psychotics
4.2.2.2. Second generation anti-psychotics
4.2.2.3. Electroconvulsive therapy (ECT)
4.2.2.4. Interaction of anti-psychotic medications with substance
of abuse and medicines used for its management
4.2.2.5. Duration of use of anti-psychotics
4.3. Psychosocial measures
4.3.1. Combined Motivational Interviewing and Cognitive Behavioural
Interventions
4.3.1.1. Basic principle
4.3.1.2. Evidence base
4.3.2. Modified Cognitive-Behavioural Therapy (CBT)
4.3.3. Dual Recovery Therapy (DRT)
4.3.4. Modified Motivational Enhancement Therapy
4.3.5. The Substance Abuse Management Module (SAMM)
4.3.6. Self-help groups

4.4. Integrated interventions

4.4.1. Basic principle
4.4.2. Evidence base
4.5. Assertive outreach
5. Service delivery related issues
5.1. Service delivery formats
5.2. Cost effectiveness related issues
6. Special populations
6.1. Prison population
6.2. Homeless population

EXECUTIVE SUMMARY
The term 'dual diagnosis' refers to the co-occurrence of at least one psychoactive
substance use disorder and at least one non-substance psychiatric disorder. Persons
with dual diagnoses, in general, pose certain unique assessment and management
challenges. This is also true for persons with dual diagnoses who have psychotic
disorder as the psychiatric disorder. With respect to the management of persons with
dual diagnosis (having psychotic disorder as the psychiatric disorder) the following
recommendations can be made -
l Detailed history and physical examination should be undertaken (S)
l Risk for violence towards self or others need to be evaluated (S)
l Rating scales should be applied (B)
l Routine and special investigations should be performed as appropriate (B)
l Motivational interviewing can be used to improve retention in treatment and
outcome (A)
l Motivational interviewing techniques may be modified to suit needs of psychotic
dual diagnosis patients (C)
l Most of the medications used for management of substance use disorders remain to
be systematically studied in psychotic dual diagnosis patients
l Naltrexone (A), acamprosate (A) and disulfiram (A) are effective in management of
alcohol use disorders
l Varenicline (A) and Bupropion (sustained release) (A) are effective in management of
tobacco use disorders
l Most of the first generation anti-psychotics and many of the second generation anti-
psychotics remain to be systematically studied in psychotic dual diagnosis patients
l Atypical antipsychotics are considered the first line of management in psychotic dual
diagnosis patients (D)
l Risperidone (A), olanzapine (A) and flupenthixol (B) are effective in management of
psychotic dual diagnosis patients
l Haloperidol (A), risperidone (A), olanzapine (A) and flupenthixol (B) are effective in
reducing substance use among psychotic dual diagnosis patients
l Long acting depot preparations may be used in case of compliance issues (D)
l There is some support for use of electroconvulsive therapy, but there is a need to
further research its role in psychotic dual diagnosis patients (C)
l Integrated psychosocial management is found to be better than individual stage-wise
management (B)

lAssertive outreach to improve engagement with treatment services has been found to
be helpful (B)
lCognitive behavioural interventions, social skills training and group interventions
have also shown benefit in dual diagnosis patients with psychotic disorders (B)
lVarious Psychosocial treatments work to similar extent for dual diagnosis patients
with psychosis (A)
l Contingency management may be useful for homeless dual diagnosis patients (A)
lHousing first approach requires further consideration as a harm reduction approach
in homeless population (B)

1. INTRODUCTION
1.1 CONCEPT OF DUAL DIAGNOSIS
The term 'Dual diagnosis' has been defined in various ways. It generally refers to the
presence of at least one (psychoactive) substance use disorder (SUD) and one
psychiatric disorder in the same person.1,2 Previously various terms have been used to
represent this co-occurrence of substance use disorders and psychiatric disorders. These
include Mentally Ill Chemical Abusers (MICA), Chemical Abusing Mentally Ill (CAMI),
Mentally Ill Substance Abusers (MISA), and Substance Abusing Mentally Ill (SAMI).
Over the past few years the terms 'Individuals with Co-occurring Psychiatric and
Substance Use disorders (ICPSUD)' and'Co-occurring disorders' are beign increasingly
used to represent those having both substance use disorders and psychiatric disorders.
For the purpsoe of the current guidelines the term 'dual diagnosis' shall be used to
represent this set of population as it coninues to be one of the most commonly used
terms in medical lietrature.
Individuals with a wide range of psychiatric disorders are more likely to have a co-
morbid substance use disorders (SUD) compared to the general population. Similarly,
those having a substance use disorder have increased chances of having a co-morbid
psychiatric disorder. Substance use disorders and psychotic disorders tend to co-occur
together3,4,5 and this co-morbidity is the focus of the current chapter.
The co-occurrence rate of SUD and psychotic disorders is greater than what would be
expected by chance. There are different possible reasons for this greater by chance
association of SUD and psychiatric disorders.6 These are represented by the common
factor model, bidirectional model, secondary substance use disorder model and
secondary psychiatric disorder models. The general issues and concepts of dual
diagnosis are applicable to the co-morbidity of substance use disorders and psychotic
disorders. These have been covered in the previous clinical practice guidelines for the
assessment and management of substance use disorders published by Indian Psychiatric
Society.7
1.2 EPIDEMIOLOGY OF DUAL DIAGNOSIS: PSYCHOTIC DISORDERS
Studies conducted worldwide have shown high rates of co-occurrence of SUD
associated with any psychiatric disorder. This is especially true for the clinical
population based studies. The rate of co-occurrence of SUD and psychiatric disorders
has varied from 15% in the general population to 80% in clinical samples from both
mental health and addiction treatment settings. However, few of these studies have
specifically calculated the prevalence of the co-morbidity of SUD with a psychotic
disorder. Even the studies that have analyzed the rate of this co-occurrence have been
limited by small sample size. Epidemiological studies that have assessed co-morbidity
of substance use disorders with psychotic disorders and found that alcohol and drug
dependence are twice as common in persons with a psychotic disorder.9

The Epidemiological Catchment Area (ECA) study revealed that 37% of people with
alcohol use disorders and 53% with other drug use disorders had co-morbid psychiatric
conditions. Amongst people with the diagnosis of schizophrenia, 47% had a substance
abuse or dependence disorder. Individuals with a diagnosis of schizophrenia were also
three times more likely to be alcohol abusers and six times more likely to abuse other
substances as compared to those without schizophrenia.10 It also estimated that even
after adjusting for baseline psychopathology and socio-demographic variables a
lifetime diagnosis of alcohol abuse/dependence predicted an eight-fold increased risk
of reporting at least one psychotic symptom in the follow-up period. Rates of cigarette
smoking among people with schizophrenia were between 70 and 88%.10
The National Co-morbidity Survey (NCS) also reported that alcohol and drug use
disorders are quite often co-morbid with other psychiatric disorders. In the revised NCS
(NCS-R), the prevalence rate for co-morbid SUD with non-affective psychosis over the
lifetime was 26.8% and prevalence in the year prior to the assessment was 15.6%.11
The studies that have focused specifically on psychotic disorders (including
schizophrenia) also have found high co-morbidity of psychotic disorders12 and
substance use disorders.12 In the Clinical Antipsychotic Trials in Intervention
Effectiveness (CATIE) study,12 at least one substance abuse or dependence was reported
in 60.3% of the sample.In an epidemiologically representative British sample of patients
with first episode psychosis Barnett et al.13 found the prevalence of substance use to be
twice as much as in the general population. Cannabis and alcohol were the most
frequently abused substances with 38% reporting polysubstance abuse. Kavanaghet
al.14 reported on substance use related variables in an Australian sample of patients with
both affective and non-affective psychosis. The prevalence of substance use disorders
was comparable in both groups with men having greater prevalence than women.
Younger age group was associated with use of illicit drugs whereas lower educational
attainment was associated with cannabis use. Addington et al.15 studied patients
admitted to an early psychosis program in Canada and confirmed earlier reports of
greater prevalence in men and younger age groups. The most prevalent substances were
alcohol and cannabis, in keeping with several previous observations.
There is a relative paucity of studies from India with regard to epidemiology co-
occurring SUD and psychotic disorders. Though characteristics of Hemp Insanity had
been described from India more than 80 years ago,16 there have been no
epidemiological studies that have systematically assessed the prevalence of co-morbid
SUD and psychotic disorders in general population. The prevalence of SUD among
persons diagnosed with psychotic disorders has been found to vary across clinical
population based studies. In a study conducted in central India, 54.3% of consecutively
admitted male schizophrenia patients were found to have an additional substance use

disorder17. Another study found substance use disorders apart from tobacco to be
present in less than 20% of the sample of patients with psychotic disorders.22 A study by
Basu et al found that psychotic disorders were present in about 3% of patients treated for
substance use disorders in a de-addiction centre. Another study found that psychotic
disorders was present in about 2% of patients being treated for alcohol use disorder.19
The course of the psychotic disorder had been reported not to be associated with
substance use in a previous study from India.20 The varied findings observed across these
studies are, in part, reflection of the different settings across which these studies have
been carried. Additionally, the study criteria, diagnostic paradigms used and sample
selection were also different across these studies. There is a need for representative
community based epidemiological studies to ascertain the rates of co-morbid substance
use disorders and psychotic disorders in the country.
1.3 IMPORTANCE OF DUAL DIAGNOSIS: PSYCHOTIC DISORDERS
Substance misuse has been identified as both a risk factor for onset as well as
progression of psychiatric disorders.11 On the other hand, impaired psychological status
may also contribute to relapse or an increase in substance use. Substance abuse is
associated with a wide range of deleterious effects in persons with a psychotic disorder.
Co-morbid SUD in persons with psychotic disorders (including schizophrenia) makes
them vulnerable even to premature death due to various factors such as vulnerability to
medical illnesses, accidental deaths, and suicide.21,22 Thus, appropriate recognition and
management of dual diagnosis is of paramount importance.
Additionally, co-morbid SUD and psychotic disorders poses various clinical challenges
during management. First, the motivation of patients with substance use disorders and
psychotic disorders may be low.23 This has been attributed to the perceived benefits as a
consequence of substance use including relaxation, elevation of mood, and countering
dysphoria in some of the previous studies.24,25 Second, engagement into the treatment
process might be difficult on the account of paranoia towards treatment services, and
fear of forced detention and coercive treatment. Also, patients with dual diagnosis that
includes psychosis may have poor insight into their illness or may not regard the
substance use as a problem. Additionally, stigma associated with both the disorders may
deter the patients from utilizing the available services.26 The risk of suicide, violence and
the presence of medical co-morbidities may be higher among patients with dual
diagnosis as compared to the patients with the either of the two disorders.22,27,28,29 The risk
of therapeutic non-adherence is high,30 and so is the chance of occurrence of social
problems like homelessness and social isolation.31 The patients with substance use and
psychotic disorders have a poorer prognosis as compared to patients with either SUD or
psychosis, as they are likely to be hospitalized at an earlier age, have longer durations of
illness and hospital stay, and frequent relapses and hospitalizations.,32,33 These factors

make the treatment of patients with substance use disorders and psychosis more
challenging than that of either disorder alone. This justifies the need for separate
guidelines for the treatment of co-occurring SUD and psychotic disorders. The dual
diagnosis of SUD and psychotic disorders shall be referred to as 'psychotic dual
diagnosis' or 'dual diagnosis: psychotic disorders' in the subsequent sections.
2.1. OVERVIEW OF THE GUIDELINES
Management of dual diagnoses in general and psychotic dual diagnoses in particular,
can be challenging. The current guidelines aim to offer guidance to clinicians who
manage patients diagnosed with both substance use disorders (SUD) and psychotic
illnesses. This shall include persons who have both SUD and psychotic disorders
irrespective of the nature of association between these two disorders.
2.2. SCOPE OF THE GUIDELINES
The current guidelines are aimed primarily at clinicians who deal with patients with co-
morbid SUD and psychotic disorders. However, the clinicians should keep in mind the
specific characteristics of the patients and the treatment setting before applying these
guidelines to individual patient. In other words, some degree of fine tuning or
individualization may be needed on a case to case basis. Finally, the treating clinician
must take into consideration the more recent evidence that would have accumulated
since writing of these guidelines.
These guidelines are meant for application by qualified and trained clinicians in de-
addiction centers and general hospital treatment settings, though it may be applicable in
other settings as well. The guidelines mainly focus on management, although some
relevant discussion on assessment is also included. The guidelines shall address the
issues specific to the psychotic dual diagnosis. The issues related to assessment and
management of SUD, in general, have been covered in the 'Clinical Practice Guidelines
for the Assessment and Management of Substance Use Disorders Treatment' published
by Indian Psychiatric Society (IPS) and can be accessed from there.34 Also, general issues
related to assessment and management for dual diagnosis have also been covered in
'Clinical Practice Guidelines for the Assessment and Management of Substance Use
Disorders Treatment' published by Indian Psychiatric Society (IPS) and can be accessed
from there.7
2.2.1. PSYCHOTIC DUAL DIAGNOSIS
For the purpose of the current guidelines 'psychotic dual diagnosis' shall refer to the co-
occurrence of one SUD and a psychotic disorder in the same individual. The dual
diagnosis of SUD and psychotic disorders shall be referred to as 'psychotic dual

diagnosis' or 'dual diagnosis: psychotic disorders' in the subsequent sections. The

psychotic disorders shall include different non-affective psychotic disorders including
schizophrenia.
2.3. METHODOLOGY OF GUIDELINE DEVELOPMENT
The guideline attempts to collate the findings from studies relating to psychotic dual
diagnosis and draw conclusions and recommendations from them. Relevant literature
was identified through a search on PubMed, PsycINFO, EMBASE and Google Scholar.
The search was carried out in June 2015. Using MeSH terms “Diagnosis, Dual
(Psychiatry)” and “Psychotic Disorders”, “Schizophrenia”, “Induced Psychosis”,
“Persistent Delusional Disorder”, and Boolean operator AND, 1066 abstracts were
identified. Of these, 39 were clinical trials, 11 were randomized trials, and 2 were meta-
analysis. Only English language peer-reviewed articles were included for the
preparation of the guidelines. Further studies were identified through cross references
and searching through other guidelines like that of the National Institute of Clinical
Excellence (NICE), Royal Australian and New Zealand College of Psychiatrists (RANZP)
guidelines, American Psychiatric Association (APA) guidelines, Queensland
Guidelines, publications of the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and the National Institute on Drug Abuse (NIDA). The Cochrane database was
also searched for relevant meta-analyses. The treatment recommendations have been
made in accordance with the quality of evidence. To maintain uniformity and quality,
the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument was used
in preparing the guidelines. The strength of recommendation was based on the study
design and other merits of the publication (table 1).
Table 1 : Methodology of guideline development - Salient Features
Data base searched PubMed

l
PsycINFO
l
EMBASE
l
Google
l Scholar
Search terms used^ Diagnosis,
l Dual (Psychiatry)”
Psychotic
l Disorders”
Schizophrenia”
l
Bipolar disorder”
l
Induced psychosis”
l
Persistent delusional disorder”

l
Other sources of information National

l Institute of Clinical Excellence
(NICE) guidelines

Other sources of information Royal

l Australian and New Zealand College of
Psychiatrists (RANZP) guidelines
American Psychiatric Association (APA)
l
guidelines
Queensland Guidelines
l
Publications of the National Institute on Alcohol

l
Abuse and Alcoholism (NIAAA)
Publications of the National Institute on Drug
l
Abuse (NIDA)
Framework for writing Appraisal

l of Guidelines for Research &
the guidelines Evaluation II (AGREE II) Instrument
^MeSH (Medical Subject Headings) search terms
3. ASSESSMENT AND FORMULATION

3.1. GENERAL ISSUES
For a detailed description on clinical assessment of substance use disorders and dual
diagnosis one is advised to refer to the 'Clinical Practice Guidelines for the Assessment
and Management of Substance Use Disorders Treatment' published by Indian
Psychiatric Society (IPS).7 The current section presents only the salient aspects relevant
to the patient with psychotic dual diagnosis.
The assessment of patients with psychotic dual diagnosis patients encompasses both
substance use and psychiatric disorder related issues. Prioritizing treatment strategies
based on the relative urgency of various issues and needs has to be carefully
undertaken. It is also influenced by the preference and expertise of the treating
psychiatrist. The psychotic symptoms may resemble those of an acute psychotic
episode to one of a more chronic psychosis with variable affective content. Moreover,
the severity and quality of the substance use disorder also varies across patients. Finally,
the directionality of 'cause and effect' of substance use and psychosis in itself adds
another dimension to the complexity.21
A simple way of prioritizing the various aspects of patient care in a case of psychotic
dual diagnosis is based on Ries typology for dual diagnosis.35 This approach shall entail
consideration of all symptoms and clinical needs under two heads – substance use
related and psychotic disorder related. Each of these categories is then considered as
being high priority and low priority, yielding four possibilities. These shall include-
'high severity psychotic disorder – high severity substance use disorder'; 'low severity
psychotic disorder – high severity substance use disorder'; 'high severity psychotic
disorder - low severity substance use disorder'; and 'low severity psychotic disorder -

low severity substance use disorder'. This approach although simple, provides valuable
guidance on prioritizing the various clinical needs of the patient.1
3.2. TREATMENT AIMS / GOALS
The aims of treatment of psychotic dual diagnosis are as follows:36,37,38
l Address acute and life threatening conditions (substance intoxication and
withdrawal, acute psychiatric symptoms like suicidality, co-morbid medical illness)
l Promote reduction/abstinence from substance of use
l Control the symptoms of psychiatric disorder
l Address the co-morbid medical illnesses, if any
l Address psychosocial issues
l Increase motivation
l Enhance coping and inculcate relapse prevention skills
l Provide psycho-education regarding illness, ensure compliance, regular follow-ups
l Improve socio-occupational functioning
l Promote maintenance of recovery through continued treatment and/orparticipation
in self-help groups
l Ensure community re-integration and social/occupational rehabilitation
The goals of treatment may be divided into short and long term goals for the sake of
convenience36. The short term goals include management of acute psychotic phase (with
management of associated agitation, aggression and disruptive behaviour) along with
management of intoxication, withdrawal and imminent medical issues. A rather unique
problem faced in treating psychotic dual diagnosis patients is their lesser engagement in
treatment and low motivation to reduce substance use.39 Presence of acute psychotic
symptoms and impaired judgment result in lower levels of motivation to reduce
substance use which in turn can destabilize the psychotic symptoms. This can initiate a
vicious feed-forward cycle were psychotic disorders and accompanying substance use
fuel each other and hamper improvement. Motivation enhancement and efforts to
retain the patient in the treatment facility thus assume significant importance in this
group of patients. However one must chose the appropriate time for such interventions.
Long term treatment goals are maintenance of abstinence, relapse prevention, control of
features of psychotic disorders and socio-occupational rehabilitation.
3.3. DECIDING TREATMENT SETTING
Outpatient setting, inpatient setting, day care setting amongst others are some of the
common settings where patients with psychotic dual diagnosis are likely to be treated.
This, in turn, could be located in an exclusive de-addiction facility, a general psychiatric

care facility or a specialized dual diagnosis treatment setting. The decision about
treatment setting needs to take care into account various factors. These include-
l Nature of acute psychiatric symptoms i.e. active psychotic symptoms
l Suicidality and self-harm attempts
l History or likelihood of future violence
l Severity of withdrawal symptoms/ intoxication
l Associated medical illnesses
l Severity of substance dependence
l Prior abstinence attempts
l Level of motivation of the patient
l Presence of social supports
l Patient and physician preference
In psychotic dual diagnosis patients, presence of active psychotic symptoms, associated
aggression and unmanageability can pose a threat to patient and/ or others. Hence an
inpatient treatment setting is often warranted in such situations.
3.4. ASSESSMENT OF DUAL DIAGNOSIS: PSYCHOTIC DISORDERS
3.4.1 GENERAL OVERVIEW
Assessment is a continuous process as new information may emerge at any point in the
course of treatment. Initial assessments are carried out with an aim to reach at a working
(definitive/ provisional or tentative) diagnosis and formulate a management plan. The
subsequent assessments are made to confirm the diagnosis (if not definitive), fill in the
gaps in information, carry out specialized assessment (as family dynamics etc.), and
observe response to interventions (including effects and side effects).Special attention
must be paid in cases of psychotic dual diagnosis patients with regards to the risk of
harm to self or others. Assessment typically includes history taking, physical
examination, mental status examination, use of scales and instruments, psychological
assessment, and relevant investigations. These steps are summarized in Figure 1.
3.4.2. CLINICAL HISTORY
In psychotic dual diagnosis patients, clinical history should be obtained from multiple
sources including patient, family members, significant others including friends and
medical records). Other sources of information like previous medical records should be
carefully reviewed. Efforts should be made to obtain information from co-workers, law-
enforcement officials (in case of legal repercussions related to substance use, violent
behaviour) to obtain a clear picture of the clinical symptoms and dysfunction.

Sources of information: Patient, Family Members,

History
Significant others including friends, Medical records, etc.
To be repeated as needed and indicated
Physical examination Signs of intoxication, withdrawal; medical complications
Mental status Psychotic disorder; co-morbid psychiatric disorders; risk of

examination violence (towards self and others); level of motivation
Investigations
(biochemical/neuro For detection of substance; for medical complications
imaging, etc)
Psychological For additional information on relevant psychological issues

assessment
Rating scales For rates severity; monitor response to therapy
Fig 1 : Assessment of a case of psychotic dual diagnosis
A detailed history regarding substance use should typically include the age of initiation,
frequency and amount of use, development of various features of 'addiction', last dose,
motivation, complications due to substance use in various domains (physical,
psychological, financial, social, familial, vocational and legal), abstinence attempts and
reasons for relapse. History of psychiatric illness should be ascertained including onset,
progression, course, severity and dysfunction.
Short lasting psychotic symptoms can be seen in the context of intoxication and must be
carefully delineated from a psychiatric disorder. Additionally, efforts should be made to
ascertain the possibility of any causal association (and directionality of causation)
between the SUD and psychotic disorder. Efforts should be made to delineate the
presence of an independent psychotic disorder from a substance induced psychotic
disorder. Temporal sequence of development of symptoms, and the course of
psychiatric symptoms in a controlled setting ensuring abstinence provide valuable clues
in establishing this distinction. This can have relevant treatment implications as
substance induced psychotic disorders tend to be self remitting once the offending
substance use stops. Relevant history to negate the possibility of delirium or organic
diseases presenting with psychiatric manifestations must also be clearly obtained.
Other aspects of the history like treatment history, medical history, family history, early

developmental history, educational, occupational history, marital history and

personality profile can help gain valuable insights into the patient's background. The
social supports and key figures in patient's life can also be assessed. The family
dynamics, family members' understanding of the patient's psychotic disorder and the
presence of expressed emotions, interpersonal conflicts and familial dysfunction
consequent to patient's illness need to be assessed. The chief care giver(s) of the patient
must be identified in order to ensure their participation in the treatment process, ensure
compliance to medications and regular follow up and to psycho-educate them
regarding the expected course and prognosis of the patient.
Though the first contact may yield a considerable part of the history, crucial elements
may also emergence later with improved therapeutic alliance with the patients and
information from other sources.
3.4.3. PHYSICAL EXAMINATION
Detailed physical examination forms an important part of evaluation of the patient with
psychotic dual diagnosis. Signs of intoxication and withdrawal are to be carefully
looked into. Findings would depend upon the nature of substance used. Thus typical
findings may include injection marks in case of an injecting drug user, tremors in
alcohol withdrawal, and discoloured teeth in case on nicotine use. Neurological
examination must also be carried out to rule out presence of focal deficits and other
neuropsychiatric manifestations.
3.4.4. ASSESSING RISK
In psychotic dual diagnosis patients assessing risk of violence and suicide forms an
important part of assessment (table 2).
Table 2 :
Risk factors for violence and suicidality among psychotic dual disorder patients
Risk factors for violence Risk factors for suicidality
Co-morbid
l substance use and Co-morbid
l substance use and psychotic
psychotic disorder disorder
Male gender
l Presence of intoxication or severe withdrawal
l
Personality disorder
l Male gender
l
Past history of violence
l Extremes of age
l
Presence of stressors
l Presence of chronic co-morbid medical
l
Presence of delusions and
l conditions, particularly painful
hallucinations with threatening and Presence of depressive symptoms,
l
persecutory content Hopelessness
l
Command hallucinations
l Personality disorder and impulsivity
l
Previous history of suicidal attempts
l
Presence of clear suicidal plans
l

3.4.4.1 VIOLENCE: Presence of co-morbid substance use29 along with a psychotic

disorder has been identified as a risk factor for violent behaviour.41 Some of the other risk
factors for violence include male gender, presence of personality disorder, past history
of violence, presence of stressors, presence of delusions and hallucinations with
threatening and persecutory content and command hallucinations.41
3.4.4.2 SUICIDALITY: A number of risk factors for suicide have been identified in
patient with dual diagnosis. As stated above for risk of violence, the presence of co-
morbid substance use disorder along with a psychotic disorder in itself is known risk
factor for suicide. Presence of intoxication or severe withdrawal, male gender, extremes
of age, presence of chronic co-morbid medical conditions, particularly painful,
presence of depressive symptoms, hopelessness, personality disorder and impulsivity,
previous history of suicidal attempts and presence of clear suicidal plans are some of the
other risk factors.22
3.4.5 RATING SCALES
Rating scales are useful for assessing the severity of problems and monitoring treatment
response over time. Some of these scales have been valid ated in a population of
patients with dual diagnoses as well. The Dartmouth Assessment of Lifestyle Instrument
(DALI) is an 18-item interviewer administered tool42 that can be used as a screening
instrument for substance use disorder in the psychiatric population. It takes about 6
minutes to complete and was formed from the most validated questions of 10 robust
screening questionnaires for substance use disorders. It primarily screens for alcohol,
cannabis and cocaine use disorders. Thought disorder subscale of Brief Psychiatric
Rating Scale (BPRS) and Beck's Depression Inventory (BDI) can be used validly in dual
diagnosis populations.43
The Chemical Use, Abuse and Dependence (CUAD) scale is a brief, reliable and
validated tool for the identification of substance use disorders in severely mentally ill in-
patients and takes about 20 minutes to administer.44
Diagnostic instruments such as the Psychiatric Research Interview for Substance and
Mental Disorders (PRISM) may also be used. PRISM also attempts to differentiate
between substance induced and independent psychiatric disorder and has been
validated in large epidemiological studies.45 Other specific scales and interview
schedules46 used for either psychotic disorders or substance use disorders may
obviously be used in combination. Some of the commonly used scales are listed in box
1. However, there is limited information on use of these instruments in Indian settings.
3.4.6 INVESTIGATIONS
Investigations of various kinds may be indicated among patients with psychotic dual
diagnosis.27 While these investigations play little role in establishing in refuting the

Box 1. Commonly used rating scales/ diagnostic instruments for the assessment of
dual diagnosis patients
l Dartmouth Assessment of Lifestyle Instrument (DALI)
l Brief Psychiatric Rating Scale (BPRS)
l Beck's Depression Inventory (BDI)
l Chemical Use, Abuse and Dependence (CUAD) scale
l Psychiatric Research Interview for Substance and Mental Disorders (PRISM)
diagnosis for with SUD or psychotic disorders these are important to identify presence
of co-morbid medical disorders (as a complication of SUD or otherwise); confirming(or
refuting) presence of substance in body fluids, monitoring treatment adherence,
monitoring side effects of treatment among others.
The investigations for SUD are guided mainly by the nature and route of substance
being used. Complete hemogram, renal function tests, liver function tests, blood sugar
and electrolytes are some of the commonly requested investigations. In patients with
alcohol use disorders, liver function tests may need to be supplanted by additional
investigations such as ultrasound abdomen, serum ammonia, upper GI endoscopy. In
case of injecting drug users, tests for hepatitis B and C, HIV may be indicated. A urine
screen for various substances in case of an unclear history or to additionally buttress
historical findings may also need to be performed. Those prescribed anti-psychotic
medications need to be monitored for blood glucose, lipid profile and liver function.
3.5 RECOMMENDATIONS FOR PRACTICE
Box 2. Recommendations for practice with regards to assessment for psychotic

dual diagnosis
l Detailed history and physical examination. (S)
l Risk for violence towards self or others need to be evaluated. (S)
l Application of rating scales. (B)
l Performing routine and special Investigations as appropriate. (B)
The alphabet in parenthesis represents strength of evidence (for details refer to the
introductory chapter)
4. INTERVENTIONS IN PSYCHOTIC DUAL DIAGNOSIS

The current section deals with salient aspects of management of psychotic dual
disorders. This includes management of SUD and management of psychotic disorder.

Only the issues specific to the psychotic dual diagnosis shall be discussed in this section.
Management of various SUD and dual diagnosis have been addressed in the 'Clinical
Practice Guidelines for the Assessment and Management of Substance Use Disorders
Treatment' published by Indian Psychiatric Society (IPS) and can be accessed from
there.7
4.1 MOTIVATION ENHANCEMENT INTERVENTIONS
A common factor contributing to the refusal or avoidance of treatment by psychotic dual
diagnosis patients is their low motivation to reduce substance use. Lack of insight
consequent to presence of psychotic illness, strong emotions, and the continuing resort
to alcohol and other readily available substances as self-medication are some of the
reason why these patients exhibit resistance to quitting substance use. Motivational
Interviewing (MI) has been recommended as an essential intervention in the early stages
of working with the patients with dualdiagnosis. Such an approach acknowledges that
individuals may not be aware that their substance use is causing problems for
themselves and others. They may not consider that they have a problem; even if they do,
decreasing or stopping use may not be on their agenda.44 Accessing treatment is not
considered equivalent to being motivated and activated to manage their own problems
with living. Hence, people living with SUD and psychotic disorders may require
assistance to move from the stage of pre-contemplation to that of contemplating of
change49,50,51,52,53 Motivational Interviewing (MI) emphasizes personal choice,
responsibility, and awareness of the risks and benefits of continued substance use and
helps the individual move towards the action stage and consequently bring about
changes with regards to their substance use behaviour.
4.2. PHARMACOLOGICAL MEASURES
4.2.1 FOR SUBSTANCE USE DISORDER
4.2.1.1 SHORT TERM MANAGEMENT
The short term management goals include treatment strategies to deal with intoxication
and withdrawal states and detoxification. Treatment of withdrawals should be initiated
along with the treatment of psychotic disorder.54
There are no empirical studies for withdrawal management for patients with psychotic
dual diagnosis. Use of typical withdrawal management regimens has been mentioned
for psychotic dual diagnosis patients. Also inpatient detoxification is recommended for
patients who are unable to stop/ reduce their substance use from out-patient.55 The
clinicians are advised to refer to the previous clinical practice guidelines for the
assessment and management of substance use disorders published by Indian Psychiatric
Society for detailed information on short term management of SUD.7
Cocaine and stimulant intoxication may present with symptoms of psychosis (e.g.

persecutory delusions). There are no approved pharmacological agents with clear

benefit in this condition. Acutely agitated patients are generally managed with
decreased exposure to external stimuli, reassurance, reorientation, and short term use of
benzodiazepines, if necessary.
4.2.1.1.1. INTERACTION OF ANTI-PSYCHOTIC MEDICATIONS WITH SUBSTANCE
OF ABUSE AND MEDICINES USED FOR ITS SHORT TERM MANAGEMENT
(MANAGEMENT OF WITHDRAWALS)
One must take in to consideration the possible interactions (pharmacokinetic and
pharmacodynamic) between the medications used for management of withdrawals and
the anti-psychotic medications. Some of these interaction have been summarized in
table 5. 56,57
4.2.1.2 LONG TERM MANAGEMENT
The general principles and outline of management of SUD can be accessed from the
previous clinical practice guidelines for the assessment and management of substance
use disorders published by Indian Psychiatric Society (IPS).7
4.2.2.1.1 FOR ALCOHOL USE DISORDERS
Acamprosate, naltrexone and disulfiram (more recently baclofen as well)are commonly
used medicines for long term management of alcohol use disorders. Selective Serotonin
Reuptake Inhibitors (SSRIs) and anticonvulsants such as topiramate have little evidence
to support their use as anti-craving agents. However, there is limited literature on
effectiveness of these medicines among patients with co-morbid alcohol use disorders
and psychotic disorders.
Naltrexone has been studied in patients with alcohol use disorders and
schizophrenia.58,59,60 In a retrospective study on 72 psychiatric patients treated with
naltrexone for alcohol use disorders, 82% significantly reduced their drinking.61 Open
label trial62 as well as randomized placebo-controlled double-blind trial have also
suggested that naltrexone maybe helpful in decreasing alcohol use in patients with
psychotic disorders and alcohol dependence.58,60
Clinical reports have suggested that disulfiram can precipitate a number of psychiatric
symptoms, including delirium, depression, anxiety, mania, and psychosis.62 Caution
has been expressed about the use of disulfiram in patients with psychosis due to risk of
psychosis and is a risk-benefit analysis must be conducted before taking the final
decision. Notably, a retrospective study with psychosis and alcohol use disorder
suggested beneficial effects of disulfiram in most patients with no suggestion of
increased psychosis.64 Disulfiram was found to be comparable to naltrexone (and better
than placebo) in a randomized controlled trial among patients with co-morbid

psychotic spectrum disorders and alcohol abuse.65 However, one must ensure that the
patient is capable of providing written informed consent before disulfiram therapy is
instituted.66
Acamprosate was found to be safe in a randomized trial among patients with co-morbid
schizophrenia spectrum disorders and comorbid alcohol dependence. However, the
trial failed to establish superiority of acamprosate over placebo in this trial.67
Limited evidence suggests utility of baclofen in the treatment of dual diagnosis
patients.64,68,69,70
In spite of limited published literature on effectiveness of medications used in long-term
management of alcohol in patients with co-morbid psychotic dual diagnosis, these
medications are commonly used in this population.71
4.2.2.1.2 FOR OPIOID USE DISORDERS
Buprenorphine and methadone72 are the primary agents used for opioid substitution
whereas naltrexone,62,73 is the main antagonist agent used in long term management of
opioid use disorders.
Opioid substitution therapy with methadone and buprenorphine remains to be
systematically studied among psychotic dual diagnosis patients. In a small study of
methadone maintenance therapy among people with opiate dependence and
schizophrenia, the best improvement was observed among those who were prescribed
a combination of methadone and clozapine.74 In a retrospective study on
buprenorphine treatment outcome in dually diagnosed heroin dependent patients with
psychotic dual disorders were found to have comparatively lower retention rates.75
Consensus recommendations from west have supported both methadone and
buprenorphine as safe treatment options.66
4.2.2.1.3 FOR TOBACCO USE DISORDERS
Bupropion, varenicline and nicotine replacement therapy (NRT) have all been studied
for the management of tobacco dependence in patients with psychotic dual
diagnosis.76,77,78 Bupropion (sustained release) has been found to increase smoking
abstinence rates in smokers with schizophrenia.79,80 Also, it does not increase the risk of
seizures in this population group.78 However, there is limited evidence to support use of
NRT in this population with lower than expected benefits, although it has been found to
be safe and well tolerated.66 There are randomized controlled trials and observational
studies that have established efficacy of varenicline in smoking cessation among
patients with psychotic dual disorders.81,82 However, one needs to be cautious with
regards to psychiatric adverse effects reported with use of varenicline.78 There are
reports of emergence and worsening of psychosis associated with use of veranicline.83

4.2.2.1.4. FOR COCAINE AND OTHER STIMULANT USE DISORDERS

There are no approved medications for use for long term management of cocaine and
other stimulant use disorders.
4.2.2.1.5. FOR CANNABIS USE DISORDERS
There are no approved medications for use for long term management of cannabis use
disorders.
Box 3 summarizes the various pharmacological options along with the strength of
evidence in management of SUD among patients with psychotic dual disorders.
Box 3. Recommended pharmacological agents for management of SUD among

patients with psychotic dual diagnosis
l Buprenorphine (D)
l Methadone (C)
l Naltrexone (For opioid dependence) (D)
l Naltrexone (For alcohol dependence) (A)
l Acamprosate (D)
l Disulfiram (A)
l Varenicline (A)
l Bupropion(sustained release) (A)
l Nicotine Replacement Therapy (NRT) (D)
The alphabet in parenthesis represents strength of evidence (for details refer to the
introductory chapter)
4.2.2 FOR PSYCHOTIC DISORDER

The general principles and outline of management of dual diagnosis can be accessed
from the previous clinical practice guidelines for the assessment and management of
substance use disorders published by Indian Psychiatric Society (IPS).7
As has already been suggested, there are a number of limitations to the available
literature. Most of the studies assessing effectiveness of antipsychotic medicines tend to
exclude patients with co-morbid SUD and psychotic disorders.84 At present, large scale
randomized controlled trials comparing efficacy and acceptability of different
antipsychotics for management of co-occurring psychosis and substance use disorder
are lacking. Studies vary in their sample size, choice of substance use and psychotic
disorder and methodology limiting comparability. Moreover, schizophrenia remains
the commonly studied psychotic disorders in these studies and information is lacking on

other psychotic disorders. The clinicians are advised to read these guidelines in
conjunction with guidelines on management of psychotic disorders.
The management of psychotic disorder includes starting an antipsychotic
agent85,86,87,88,89,90,91 and optimal titration of dose based on the improvement of baseline
target symptoms.
4.2.2.1. FIRST GENERATION ANTI-PSYCHOTICS
There is limited literature that has explored effectiveness of first generation anti-
psychotics among patients with psychotic dual disorders. However, in spite of concerns
with regards to propensity of first generation antipsychotics to exacerbate substance use
consequent to extrapyramidal side effects and worsening of negative symptoms and
dysphoria, small open label trials have suggested favorable outcomes with regards to
co-morbid SUD among patients with psychotic dual diagnosis who were treated with
flupenthixol.92,93 Improvement in SUD was reported in spite of limited improvement in
psychotic features in one of these studies.93 However, long-acting injectable depot
risperidone was found to be associated with better substance use and psychosis
outcomes over six months in an open label randomized trial among patients with co-
morbid SUD and schizophrenia.94 Another randomized trial reported a significantly
higher reduction in craving for cocaine patients treated with haloperidol compared with
patients treated with olanzapine. However, there were no differences in SUD and
psychosis outcomes in this study.89 On the other hand, another study found olanzapine
to be associated with significant reductions in craving and SUD as compared to
haloperidol in a randomized trial among individuals with co-morbid cocaine use
disorder and psychotic disorder.86
4.2.2.2. SECOND GENERATION ANTI-PSYCHOTICS
Second generation antipsychotics have been considered as first line agents in primary
psychotic disorders because of the decreased risk for extrapyramidal side effects and
tardive dyskinesia. Some evidence suggests additional utility of these agents in treating
substance use disorders.87,90,91 Only clozapine,90,91 has been shown to be clearly more
effective than other agents, that too in those who have failed previous trials of other
medications. Some evidence, mainly from case reports and series, suggest clozapine's
beneficial role in psychotic dual diagnosis as it has additional beneficial effects on
substance use as well.95,96 However, there are no prospective, randomized controlled
trials that have established superiority of clozapine in such population.55
Risperidone was found to be associated with significantly less cue-elicited craving and
substance related relapses in a six week open label study among patients with co-
morbid cocaine use disorder and schizophrenia.97 However, there was no significant
improvement in psychotic features.A double-blind, randomized controlled trial over 14

weeks comparing the efficacy of olanzapine with risperidone in patients with co-morbid
cocaine/cannabis use disorder and schizophrenia found comparable treatment
adherence rates in the two groups. Risperidone was associated with a significantly
greater reduction in cannabis craving.98 Olanzapine has also shown to improve
retention in treatment and SUD during opioid agonist maintenance treatment in the
patients with co-morbid opioid use disorders and psychotic disorders.99 However, long-
acting injectable depot risperidone was found to be associated with better substance use
and psychosis outcomes over six months in an open label randomized trial among
patients with co-morbid SUD and schizophrenia.94 Another study found olanzapine to
be associated with significant reductions in craving and SUD as compared to
haloperidol in a randomized trial among individuals with co-morbid cocaine use
disorder and psychotic disorder.86
Similarly, there is some evidence that second generation anti-psychotics can have some
beneficial effect among those with psychotic disorder when used in conjunction with
nicotine replacement therapy.100
Other antipsychotics like aripiprazole and quetiapine have also been found to control
substance use and psychosis although the evidence is limited by its quantity as well as
quality.87,88
Second generation anti-psychotics have been recommended as a first line agents in
management of psychotic dual disorders.55 While there is some evidence to suggest
benefit of second generation antipsychotic over first generation antipsychotics,
comparison of various atypical antipsychotics has not established or refuted superiority
of one medicine over another equivocally. In view of the potentially life threatening
adverse effects associated with use of clozapine, other second generation anti-
psychotics such as olanzapine and risperidone have been recommended as preferred
medications for this population.55 Among these agents, choice of a particular agent may
depend upon the desired side-effect profile, availability and cost of the medications.
Long-acting injectable antipsychotic medication may be considered for patients with
recurrent relapses related to therapeutic non-adherence.93,94
The recommendations with regards to use of anti-psychotics in management of
psychotic dual diagnosis have been presented in Table 3. These recommendations need
to be seen in light of limitations of the existing evidence (including limited research on
anti-psychotics in this population) as highlighted earlier.
4.2.2.3 ELECTROCONVULSIVE THERAPY (ECT)
The efficacy of ECT has been well established in patients with psychotic disorders.101,102
ECT is often reserved for patients who do not respond to less invasive methods of
treatment. It is also considered as a viable treatment option for patients who present with
catatonia or have high risk of suicide or violence. The literature on dual diagnosis
psychotic patients has also supported the use of ECT as an effective treatment modality,
but has been restricted to case reports and case series.103,104
Table 3 :
Recommended anti-psychotic medications and Electroconvulsive Therapy (ECT) for
management of SUD among patients with psychotic dual diagnosis
A. Effectiveness with regards to psychotic features

Flupenthixol
l (B)
Other
l First generation anti-psychotics (D)
Clozapine (C)
l
Olanzapine (A)
l
Risperidone (A)
l
Aripiprazole (C)
l
Quetiapine (C)
l
Other second generation anti-psychotics (D)

l
Depot anti-psychotics (A)

l
Electroconvulsive Therapy (ECT) (C)

l
B. Effectiveness with regards to SUD

Flupenthixol
l (B)
Haloperidol
l (A)
Clozapine (C)
l
Olanzapine (A)
l
Risperidone (A)
l
SUD- Substance Use Disorder

The alphabet in parenthesis represents strength of evidence (for details refer to the introductory
chapter)
4.2.2.4. INTERACTION OF ANTI-PSYCHOTIC MEDICATIONS WITH SUBSTANCE

OF ABUSE AND MEDICINES USED FOR ITS MANAGEMENT
Anti-psychotic medicines used for management of psychosis can have potential
interactions with substance of abuse as well as medicines used for its management.66
Opioid agonists and partial agonists can contribute to the sedation and constipation
with anti-psychotic medications. Naltrexone has not been found to have any significant
interaction with anti-psychotic medications.66 Medications such as ziprasidone (that
prolong the QT interval) should better be avoided in patients with prolonged baseline
QTc intervals and co-occurring alcohol and cocaine use. Tobacco smoking increases
the rate of metabolism of the antipsychotic medications (such as clozapine, olanzapine,

haloperidol, fluphenazine, chlorpromazine, thioridazine) metabolized through the

P450 1A2 isoenzyme by about 50%. Anti-psychotic medicines that are likely to lead on
to liver disease, cardiac disease or lowering of seizure threshold should be used
cautiously among those patients with SUD whose substance of abuse has lead to
impaired functioning of these bodily systems and organs. While presence of these
medical conditions is not an absolute contraindication to use of anti-psychotics one
must make a risk-benefit- analysis prior to instituting treatment with these medications.
In case use of such anti-psychotics is warranted in such patients, it should be initiated
under close medical supervision with regular monitoring of the functioning of such
bodily systems and organs. Interactions of anti-psychotic medications with substance of
abuse and medicines used for its management have been summarized in tables 4&5.
Table 4 : Interaction between psychoactive substances and anti-psychotics

Psychoactive substance Anti-psychotic Interaction
Alcohol and cocaine Ziprasidone Prolonged baseline QTc
intervals specially among
those with prolonged baseline
QTc intervals
Tobacco smoking Clozapine, olanzapine, Increased metabolism
haloperidol, fluphenazine,
chlorpromazine,
thioridazine
Various psychoactive Various anti-psychotics Aggravated insult to bodily
substance impacting impacting bodily systems and organs
bodily systems and organs systems and organs
Table 5 :
Interaction between medications used for management of withdrawal
from substances and anti-psychotics
Medication used for Anti-psychotic Interaction

management of withdrawal
Benzodiazepines Antipsychotics with Increased sedation
sedating effect cognitive dysfunction
Methadone Quetiapine Increased plasma
methadone concentrations^
Methadone Antipsychotics with Increased sedation
Buprenorphine Antipsychotics with Increased sedation

Medication used for Anti-psychotic Interaction

management of withdrawal
Methadone Risperidone, other Possibly increased plasma
phenothiazines concentrations^
Baclofen Antipsychotics with Increased sedation
Clozapine#
Nicotine/ tobacco smoking* Clozapine, haloperidol Decreased concentration of\
antipsychotics
^ pharmacokinetic interaction
*Polycyclic aromatic hydrocarbons in tobacco smoke primarily implicated; nicotine alone has
some evidence from animal studies as enzyme inducer.
#Clozapine and baclofen additionally interact at the GABA B receptor, exact clinical
implications not known.
4.2.2.5 DURATION OF USE OF ANTI-PSYCHOTICS

Following the first psychotic episode, antipsychotic medication is usually continued for
a period of around 1-2 years, although long-term therapy is commonly recommended
for patients with recurrent illness.105,106,107 Antipsychotics prevent relapse in patients with
remitted positive and mood symptoms, and maintenance treatment helps to reduce
symptoms in patients with chronic illness. These drugs enable many patients who
previously would have been institutionalized to live in the community. Regular
physical examination and relevant investigations must be carried out to monitor the
side-eff\ects.108,109,110
4.3 PSYCHOSOCIAL MEASURES
In comparison to those with substance abuse alone, patients with co-morbid SUD and
psychotic disorders have relatively less motivation to change, are harder to engage,
drop out of long-term programs more easily, and make slow progress. In addition to
pharmacotherapy, psychosocial interventions are considered important to improve
motivation, treatment adherence and prevent relapse.48,51,52,53 The details on
psychosocial measures in management of SUD can be accessed from the previous
clinical practice guidelines for the assessment and management of substance use
disorders published by Indian Psychiatric Society (IPS).7
In context of psychotic dual disorders (among those diagnosed with schizophrenia)
Combined Motivational Interviewing and Cognitive Behavioural Interventions,
Modified Cognitive-Behavioural Therapy (CBT), Dual Recovery Therapy (DRT),
Modified Motivational Enhancement Therapy, The Substance Abuse Management
Module (SAMM), self help groups, social support interventions have been studied/
recommended.

4.3.1 COMBINED MOTIVATIONAL INTERVIEWING AND COGNITIVE

BEHAVIOURAL INTERVENTIONS
4.3.1.1 Basic principle
Motivational Interviewing is an empathic, nonjudgmental, and supportive approach to
examine the patient's ambivalence about changing substance use behaviours and help
achieve behaviour change. Cognitive Behavioural Interventions are based on the
cognitive and behavioural theories with an aim to improve self-control and social skills.
In the UK, Barrowclough et al.[86] conducted a randomized controlled trial of family
intervention in psychosis with substance misuse. The intervention, which comprised
five weekly sessions of motivation interviewing, six sessions of cognitive therapy held
every 2 weeks, and 10–16 sessions of family intervention was more effective than
routine care in improving general functioning, symptoms and days of abstinence from
substance misuse over 12 months. Another trial that involved 29 sessions of Cognitive
Behavioural Interventions and Motivational Interviewing over 9 months, with
subsequent follow-up assessments at intervention completion (9 months), one year
later, and again at 18 months post-intervention in 18 schizophrenia patients, found
significant improvements in psychiatric well-being on the DSM-IV Global Assessment
Functioning scale and fewer negative symptoms in comparison to routine care.[87]
4.3.2 Modified Cognitive-Behavioural Therapy (CBT)
Modified Cognitive-Behavioural Therapy (CBT) includes information about cravings
and triggers of drug use, and the unique difficulties associated with substance abuse for
people with schizophrenia; includes relapse prevention; motivational interviewing
strategies; social skills improvement; problem-solving strategies.111
It has been recommended by expert group on improving the care of individuals with
schizophrenia and substance use disorders.66
4.3.3 Dual Recovery Therapy (DRT)
Dual Recovery Therapy (DRT)integrates substance abuse relapse prevention,
psychiatric social skills training, Motivational Enhancement Therapy and the principles
of 12-step programs in linked group and individual treatment sessions.112


4.3.4 Modified Motivational Enhancement Therapy
In Modified Motivational Enhancement Therapy, traditional Motivational Enhancement
Therapy is modified for the patient with schizophrenia as specific strategies are
matched to different motivational levels.113
4.3.5 The Substance Abuse Management Module (SAMM)
The Substance Abuse Management Module (SAMM) is based on relapse prevention,
harm reduction, and social skills training.114
4.3.6 Self-help groups
Self-help groups for dual diagnosis provide support and education about addiction
recovery concepts. The members learn to see recovery as a way of living a meaningful
life within the limitations of their dual diagnoses. Specifically targeted self-help groups,
such as Dual Recovery Anonymous or Double Trouble in Recovery have been reported
to play an important and meaningful role in the lives of people with dual diagnoses.115
These groups offer essential social support that comes from others who fully understand
the difficulties of remaining sober, and they provide a structure for daily living, along
with a commitment to stopping substance use.
Research reveals that clients who consistently attend these self-help groups for a year or
more achieve reduced substance use outcomes. The traditional 12-step programs on
which these programs are based may need modification for the people with dual
diagnoses; the limitations of social and emotional expression among many people with
schizophrenia do not fit with the Alcoholics Anonymous custom of talking about
intimate aspects of oneself in a group.116
A Cochrane review of 32 RCTs failed to find compelling evidence to support any of the

psychosocial interventions over another to remain in treatment or to reduce substance

use or improve mental state in people with serious mental illness.117 Also, none of the
aforementioned psychosocial interventions for psychotic dual disorders (among those
diagnosed with schizophrenia) have been studied in Indian setting.
4.4 INTEGRATED INTERVENTIONS
4.4.1 Basic principle
The integrated approach involves individually tailored treatments. It is focused on
preventing anxiety, emphasizes trust, understanding and learning. It is aimed at
reducing harm from substance use rather than achieving abstinence. Case management,
close monitoring, substance misuse treatment, rehabilitation, housing and
pharmacotherapy have been identified as components of integrated
approach.118,119,120,121,122
4.4.2 Evidence base
Integrated out-patient treatment has been found to be effective in engaging patients in
services, reducing substance use and sustaining remission among dual diagnosis
patients.118
4.5. ASSERTIVE OUTREACH
Assertive community treatment (ACT) is described as a structured health care service
approach to working with dual-diagnosis clients.123 The case managers are central to
client engagement, treatment, and retention. The usual case-manager responsibilities
include development of a working alliance with patients, link them into relevant other
services, and function as their advocate vis-a-vis these services and other health
professionals.
Assertive community treatment (ACT) has been found to be associated with better
outcomes with regard to substance use, quality of life, reduced hospitalization (when
base rate was high) as compared to the standard out-patient management over a three
year period.123,124
4.6. RECOMMENDATIONS FOR PRACTICE
Motivational interviewing to improve retention and outcome. (A)
l
Family motivational intervention in case of adolescents with psychotic dual

l
diagnosis. (A)
Modification of motivational interviewing techniques to suit needs of dual
l
diagnosis patients. (C)

Atypical antipsychotics are considered the first line of management in dual

l
diagnosis patients with psychotic disorders (A)
Clozapine is the only antipsychotic shown to have superior efficacy compared to
l
other atypical and typical agents (A)
Long acting depot preparations may be used in case of compliance issues (B)
l
Role of ECT needs to be further researched in dual diagnosis patients with

l
psychotic disorders (C)
Lithium and valproate may have some efficacy in reducing substance use and
l
controlling psychiatric symptoms in patients with substance use disorder and
bipolar disorder (B)
Acamprosate and naltrexone may be of benefit in alcohol use disorder among dual
l
diagnosis patients by reducing alcohol use (A)
Integrated psychosocial management is found to be better than individual stage-
l
wise management (B)
Assertive outreach to improve engagement with treatment services has been found
l
to be helpful for patients with dual diagnosis (B)
Cognitive behavioural interventions, social skills training and group interventions
l
have also shown some benefit in dual diagnosis patients with psychotic disorders(B)
There is no compelling evidence to support any one psychosocial treatment over
l
another to remain in treatment or to reduce substance use or improve mental state

in people with serious mental illness (A)
5 SERVICE DELIVERY RELATED ISSUES
5.1. SERVICE DELIVERY FORMATS
Sequential, parallel and integrated formats are the three main types of service delivery
for patients with psychotic dual diagnosis. Sequential format refers to treatment of either
substance use or psychotic disorder first followed by the other. The parallel format
means simultaneous treatment for SUD and psychotic disorder but by different teams.
Integrated format means that the same team with full coordination and integration treats
both disorders simultaneously (table 6).
Of the three formats, integrates format is regarded as the best.125 It is reported to be more
efficient and involves a flexible combination of treatment for SUD and psychiatric
disorder.
Matrix Model has been developed with an aim to manage dual diagnosis
comprehensively across a range of service delivery agencies. Psychiatric and SUD
professionals work in partnership across services and commissioning structures and
create 'nodes of integration'. These nodes of integration create a matrix by linking
through parallel-working. Although promising in its approach, further research is
required to test the effectiveness of this service-delivery model.

Table 6 : Components of integrated care for patients with dual diagnosis
Component Description
Case management Multidisciplinary
l case management
Assertive
l outreach
Close monitoring Medication

l supervision
Urine
l drug screening
Coercive approaches
l
Substance misuse treatment Motivational

l approaches
Harm reduction
l
Cognitive behavioural therapy in

l
individual, group and family settings
Self-help groups
l
Social skills training

l
Rehabilitation Provision
l of long-term support in the
community
Housing Supported
l and independent
Pharmacotherapy Provision
l of antipsychotic medication,
Improvement
l of compliance by providing
education and medication supervision
5.2. COST EFFECTIVENESS RELATED ISSUES

Compared with either SUD or psychiatric patients, patients with dual diagnosis tend to
utilize more services.126 However, interventions developed for dual diagnosis patients
(Assertive Community Treatment) have been found to be comparable to standard
management in terms of cost-effectiveness.126 The benefits in terms of cost-effectives are
even more marked for those with high severity of disorder.127 However, more research is
needed to ascertain whether the added benefits of high-intensity acute care justify the
extra costs. Psychotic dual diagnosis patients are more likely to be towards the high
severity of the spectrum and are expected to benefit from such interventions for dual
diagnosis.
5.3 RECOMMENDATIONS FOR PRACTICE
Integrated treatment of dual diagnosis clearly leads to better outcomes than other
l
formats of service delivery (A)

High-intensity service delivery improves outcomes in more severe cases (C)
l

6. SPECIAL POPULATIONS
6.1. PRISON POPULATION
Studies have reported that more than 90% of prison inmates reported drug or alcohol
use. In spite of this, only limited research on dual diagnosis has been carried out in the
prison setting. A recent review of mental health care in prisons from the Sainsbury
Centre for Mental Health (SCMH) found a 'big gap' in dual diagnosis services in prison
and a 'lack of co-ordinated care' in prison and on release for those with a dual diagnosis.
It has been found feasible to use instruments such Addiction Severity Index and Mini
International Neuropsychiatric Interview (MINI) to assess patients with dual diagnosis in
prison setting. A review of existing prison based treatments of dual diagnosis reported
that well-run treatment programs often ease the burden of correctional
administration.128,129,130 However, it has been recommended that dual diagnosis patients
should be treated in specialized facilities rather than in the jails itself.
However, management of dual diagnosis in this population group remains unexplored
in Indian setting.
6.2. HOMELESS POPULATION
Patients with a dual diagnosis are more likely to have had difficulties with education,
employment, accommodation, and hence more liable to social exclusion and
homelessness as compared to those with either a SUD or a psychiatric disorder.131 Co-
morbid substance disorder and schizophrenia has been shown to be associated with a
variety of poorer outcomes, including housing instability and homelessness. Integrated
care involving mental health, substance abuse, and housing interventions has been
reported to be beneficial among this population group.118 In fact, housing first programs
favoring immediate housing and consumer choice have been recommended as viable
alternative to standard care in this population group.131,132
However, management of dual diagnosis in this population group remains unexplored
in Indian setting.
6.3. RECOMMENDATIONS FOR PRACTICE
l Jail diversion services may reduce time spent in jail without increasing risk to the
public (B)
l Service utilization of jail diversion services is required to be improved (B)
l Contingency management may be useful for homeless dual diagnosis patients (A)
l Housing first approach requires further consideration as a harm reduction
approach in homeless population (B)

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DUAL DIAGNOSIS :
NON-PSYCHOTIC DISORDERS
SK Mattoo
Shubh Mohan Singh
On behalf of
2016
Dual Diagnosis : Non-Psychotic Disorders
CONTENTS
Executive Summary
1. Introduction
2. Scope and introduction of guideline
3. Results
3.1 General considerations and treatment setting
3.2 Screening, assessment and treatment
3.3 Mood disorders
3.3.1 Major depressive disorder (MDD) and Bipolar disorder (BPAD)
3.3.2 Pharmacotherapy
3.3.3 Psychotherapeutic and psychosocial management
3.3.4 Conclusions
3.4 Anxiety disorders
3.4.1 General considerations
3.5. Personality disorders
3.5.2 Borderline personality disorder
3.5.3 Antisocial personality disorder

EXECUTIVE SUMMARY
Dual diagnosis disorders (DD) denotes the co-existence of substance use disorders
(SUD) and other non-substance use psychiatric disorders in the same individual. Non-
psychotic DD include the co-occurrence of substance use disorders with mood
disorders, anxiety disorders, and personality disorders. The presence of DD predicts
poor prognosis with respect to both the SUD and the non-SUD. Therefore, treatment
options for DD need to be carefully considered. There is some evidence to show that the
traditional treatment models of consecutive or insulated care of the SUD and the non-
SUD may not be as effective as integrated or simultaneous care of the DD. The authors
have attempted to review this are keeping in view the requirements of the mental health
professional in India.
A review of literature reveals that there is scarcity of data. However, the following
recommendations can be made.
All patients should be screened for the possibility of DD at initial assessment unless
acute stabilization is required when this may be deferred. For this purpose, screening
instruments may be used. If there is any indication of DD, then a more thorough
assessment to confirm the diagnosis and get other relevant details should be done. The
treatment of DD should be conceptualized in two phases, acute and maintenance or
stabilization phase.
In DD with mood disorders, literature search indicates the following recommendations.
In alcohol SUD and major depressive disorder (MDD), mirtazapine, add-on naltrexone
or alone, add-on naltrexone to sertraline and add-on disulfiram as second choice can be
tried. In alcohol SUD with bipolar disorder, add-on naltrexone as first choice followed
by add-on lamotrigine or alone, add-on valproic acid or alone, add-on disulfiram as
second-choice and add-on gabapentin, add-on topiramate, lithium as third choice can
be recommended. In cannabis SUD with Bipolar disorder, add-on valproic acid to
lithium as first choice and lithium, or add-on valproic acid as second-choice may be
recommended. In Cocaine SUD with MDD, add-on risperidone or alone can be
recommended. In Cocaine with Bipolar disorder, add-on valproic acid to lithium as first
choice followed by add-on lamotrigine or alone, lithium, add-on valproic acid or alone,
add-on quetiapine or alone, add-on rispridone or alone as second choice can be
recommended. In Opioid SUD with MDD/Bipolar disorder no evidence based
recommendation is possible. However, treatment as usual for the affective disorder is
likely to be effective. As regards psychotherapy, in MDD and bipolar disorder,
motivational interviewing and Contingency management may be useful.
In DD with anxiety disorders, the evidence base is again scarce. Selective serotonin
reuptake inhibitors are likely to be affective. Benzodiazepines should not be withheld

indiscriminately. Specific psychotherapies for anxiety disorders are also likely to be

useful.
In DD with personality disorders, recommendations are possible for borderline
personality disorder and antisocial personality disorders. Interventions for SUD in
presence of personality disorders are likely to be as effective in those without
personality disorders. Dialectical behaviour therapy can be recommended for
borderline personality disorder and contingency management can be recommended in
antisocial personality disorder.

1. INTRODUCTION
Dual diagnosis disorders (DD) denotes the co-existence of substance use disorders
(SUD) and other non-substance use psychiatric disorders in the same individual.1 This
co-occurrence is observed to be much higher than that would be expected by chance
alone and about 50% of people with severe mental disorders are affected by SUD.2 This
finding has been borne out in epidemiological studies done across the world across
different diagnostic groups.3 The reasons for this association are complex and various
etiological theories have been proposed.4 It is also been observed that people with DD
have higher rates of negative outcomes such as relapses, involvement in crime,
homelessness, infections and hospitalization.5 Traditional models of psychiatric care in
which services for mental disorders and SUD run separately and parallel to each other
often prove to be less than effective in the optimum management of people with DD.
Thus, despite the heterogeneity inherent in individuals with DD, the current trend is to
consider patients with DD as belonging to a distinct group with special needs and to
integrate services in such a way that both the SUD and the psychiatric disorder are
managed simultaneously by one service with equal importance paid to both.6
Notwithstanding the clinical and public health importance of DD, research in this area
has suffered due to lack of standardised definitions and nomenclature.1,7 Major
nosological systems do not have any special category for DD and stress upon the group
of substance-induced disorders in which there is evidence of a plausible association
between substance intoxication and/or withdrawal and the mental disorder with proof
of the symptoms of the latter not being due to an independent mental disorder.8,9
In addition, other than some notable exceptions, major treatment guidelines for mental
disorders have not given adequate importance to DD.10 There are some treatment
guidelines that are exclusively devoted to DD11-14 and its assessment.15 Indian data in this
field are scarce with regards to both epidemiology and treatments.16 However, given the
rates of mental disorders and SUD in the Indian population, it is likely that DD represent
a major source of psychiatric morbidity in India as well.17
This guideline attempts to synthesize available data regarding the management of non-
psychotic DD in the form of clinical practice guidelines (CPG) that are especially
applicable to the Indian context.
CPGs are systematically developed statements to assist practitioner and patient
decisions about appropriate health care for specific clinical circumstances. The authors
have tried to maintain a high standard and quality for these guidelines. Thus, the
Appraisal of Guidelines for Research & Evaluation (AGREE) Instrument II has been used
as a template for this exercise as far as possible.18 AGREE instrument is a tool that
assesses the methodological rigor and transparency in which a guideline is developed.
We have prepared this guideline in accordance to AGREE II, the newer revised version.
We endeavoured to follow a structured and rigorous development methodology, to
conduct an internal assessment to ensure that the guidelines are sound, and to evaluate
guidelines by other groups for potential adaptation to our own context. Categories of
strength of evidence available are based upon the AGREE II guideline.19
For the purpose of this guideline, non-psychotic disorders include the group of affective
disorders, anxiety disorders and personality disorders.
We have reviewed the available literature with regards to non-psychotic disorders, DD,
substance abuse and clinical management up to July 2015. Through a process of
consultation between the authors, relevant data were retained. Treatment guidelines
were then generated on the basis of available level of evidence.
3. RESULTS
The following sections present the results of the literature review. Each section will be
followed by a section of recommendations along with strength of available evidence.
This is presented with reference to the Indian context and the proposed audience in
mind.
3.1 General considerations and treatment setting
The presentation and management of patients with DD can take place in varied settings.
These include dedicated substance abuse services, mental health services, or dedicated
DD services. The literature review reveals that there are subtle differences in
recommendations with respect to different treatment settings.12,14,15 However, the
authors opine that considering the state of mental health services in India, our
recommendations will be common with regards to treatment setting. These
recommendations can be considered appropriate for an inpatient, outpatient or
emergency mental health service that is manned by psychiatrists and other mental
health professionals.
3.2 Screening, Assessment and Treatment
Screening is the process for evaluating the possibility of the presence of a particular
problem. Assessment on the other hand is the process of evaluating the nature of that
problem and developing specific strategies.
While it is perhaps intuitive that screening and assessment should be an integral and
important part of any management protocol in DD, objective data is scarce in this
population. Treatment guidelines however explicitly mention and advocate screening
and assessment of all patients presenting at mental health and substance abuse services
for the possibility of DD unless there are immediate contraindications such as
intoxication, pain, distress, or need of emergency treatment.14,15 If present, these need to
be managed immediately.
The process should start with a proper history taking including family history, past
history, a physical examination and necessary laboratory investigations. As mentioned
before, the high degree of co-occurrence should ensure that the clinicians have a high
index of suspicion so that necessary details are enquired into and a clinical diagnosis is
possible. In case there is history of substance use in a setting of psychiatric symptoms,
the possibility of substance-induced disorders should be entertained and ruled out. This
is because these disorders are generally self-limiting.
In addition to clinical assessment, the use of appropriate screening instruments may be
recommended. These can include instruments such as K-10, PsyCheck, or MINI for
patients presenting with substance abuse related complaints or instruments such as
CAGE, ASSIST, AUDIT for patients presenting with complaints related to psychiatric
disorders other than substance use disorders.15 Indian data in this area are scarce. There
are some data with regard to use of screening instruments especially with respect to
alcohol use disorders20 and also the development of screening questionnaires in
vernacular for detection of common mental disorders21, depressive disorders22 and
alcohol dependence.23 However, these have not specifically addressed populations
with DD.
If clinical assessment, and/or screening indicate the presence of DD, a comprehensive
diagnostic assessment should be carried out for all patients.24 Several authors have
pointed out that diagnosis in DD may be difficult and may require multiple
assessments.24 This should be followed by treatment planning and outcome evaluation.
Treatment planning can vary on a case-to-case basis. Outcome evaluation should also
include documentation of current substance use patterns to evaluate the severity of
current use and to serve as a baseline for the future and pre-morbid baseline
functionality.24 The temptation to consider one of the other diagnosis as primary should
be avoided.25
Phases of treatment can be divided into acute treatment and stabilization followed by
maintenance and rehabilitation.25 Acute management involves observation, making a
diagnosis, management of acute conditions such as intoxication or withdrawal,
management of psychiatric symptoms and stabilization to as close to the baseline as
possible. Maintenance phase seeks to prevent relapse and recurrence through
continued medical and psychosocial interventions.25
Recommendations
Strength of all recommendations for this section: D
l All patients should be comprehensively assessed and screened unless acute
stabilization is required
l Initial assessment should include a proper history, clinical and laboratory evaluation
l Relevant screening instruments can be used
l Positive screening or clinical evaluation should suggest DD and a comprehensive

assessment for the same should be carried out
l Assessment of DD should include patterns of substance abuse, psychiatric
symptomatology, estimation of pre-morbid functioning
l It is useful to consider management of DD in two phases, namely acute management
and maintenance phase and rehabilitation
3.3 Mood disorders
3.3.1 Major Depressive Disorder (MDD) and Bipolar Disorder (BPAD)
MDD is commonly comorbid with SUD.26 The odds ratio for developing SUD in those
with a life time history of MDD is 1.8.27 This comorbidity also increases the cost of
treatment when compared to non-DD patients.28 The comorbidity of BPAD and SUD is
even more obvious. Early-onset BPAD seems to be strongly associated with the
development of SUD.29 The odds ratio for developing SUD in patients with BPAD can
be as high as 6.9.30 A review of literature in this area revealed that other than a recent
Canadian management guidelines for patients with mood disorders and SUD11, there is
a paucity of well-designed, randomized and controlled clinical trials in patients with
DD. Therefore, robust guidelines are difficult to arrive at.
With regards to pharmacotherapy in patients with comorbid SUD and mood disorders,
the literature review suggests that outcome measures have included the symptoms of
the mood disorder and the craving or use of substance. The literature review is as
follows.
Anticonvulsants:
There is little evidence for the use of anticonvulsants in DD patients with MDD. There
are negative Ib studies with regards to the use of carbamazepine in patients with MDD
and cocaine use.31-33 There is level 4 evidence for the use of valproate in alcohol DD.34
The evidence base for the use of anticonvulsants in DD with BPAD is no better. An
open-label, non-blinded study with 9 participants with different SUD showed the utility
of valproate in acute BPAD.35 There is a negative study for the use of carbamazepine in
cocaine users.31 There is some level II, III and IV evidence for the use of add-on
gabapentin in alcohol SUD36,37, add-on or alone lamotrigine in alcohol and cocaine
DD38-40, and add-on topiramate in alcohol DD.36,41,42
Lithium:
The evidence base suggests that lithium is not useful in MDD comorbid with alcohol
and cocaine SUD (level Ib and IV respectively).43,44

There is somewhat greater evidence for the use of lithium alone or in association with
other drugs in BPAD DD. Lithium has been shown to be effective in adolescents with
BPAD and secondary SUD (Level Ib).45 There is also some evidence base for the use of
lithium as add-on with valproic acid or alone in DD with alcohol, cannabis and cocaine
SUD (Level Ib).44-46
Antidepressants:
There is some evidence for the use of antidepressants in MDD comorbid with DD. No
studies were found for BPAD comorbid with SUD.
Among the tricyclic antidepressants, the evidence base is as follows. There is level Ib
evidence supporting the use of amitriptyline, desipramine and imipramine in DD with
alcohol SUD.47-50 Imipramine has also been used with benefit as add-on to methadone in
opioid dependence with MDD.51,52
The evidence base for selective serotonin reuptake inhibitors is also confined to MDD.
There is level Ib evidence supporting the use of fluoxetine, escitalopram, nefazodone
and sertraline in alcohol SUD comorbid with MDD.53-58
Level IB evidence also exists for the use of mirtazapine for the same indication.47, 59
Level Ib evidence exists for the use of sertraline in cocaine SUD comorbid with
depressive symptoms.60 There is also a negative study for the use of venlafaxine in
patients cocaine SUD comorbid with MDD.61
Antipsychotics:
The evidence base for the use of antipsychotics in DD MDD is meagre. There is a level 4
study supporting the use of risperidone in cocaine SUD.62
Antipsychotics have been studied more often in the context of DD BPAD. There is
evidence supporting the use of add-on and alone quetiapine and risperidone in
polysubstance abuse (level 3), alcohol, cocaine, amphetamines and
methamphetamines (level 2).62-68 However, there are negative studies with quetiapine as
well.69
Others:
The other agents that have been studied in DD MDD are buprenorphine in heroin SUD
(level 4)70, disulfiram in alcohol SUD (level 2)71, memantine in alcohol SUD (level 2)53,54
and naltrexone add-on or alone (level 2)58,72, naltrexone with sertraline.58
The other agents that have been studied in BPAD DD are add-on disulfiram in alcohol
SUD (level 2)72,73, methadone in heroin SUD (level 3)74 and add-on naltrexone in alcohol
SUD (level 2).72,75,76


There is some evidence for the role of psychotherapy and psychosocial methods of
intervention. There is an increasing use of technology and novel methods in delivering
these interventions.77-79 However, given the nature of interventions, blinding and
placebo-controlling is impossible.
Contingency management was found to be useful for improving treatment retention in
both MDD and BPAD with comorbid SUD.80
The evidence base for different psychotherapies in patients with MDD or BPAD
comorbid with SUD is as follows.
Cognitive behaviour therapy (CBT):
There are negative results reported for studies conducted for both MDD and BPAD with
comorbid SUD.81-83
Interpersonal therapy (IPT):
A preliminary report has supported the use of IPT in women with alcohol SUD and
MDD.84
Motivational interviewing (MI):
There is level 2 evidence for the use of MI in DD85,86 and level 3 evidence for use in
BPAD.85 However, when combined with CBT, MI has not been shown to be effective.87
3.3.4 Conclusions
There is a paucity of well-designed studies regarding the effectiveness of various
interventions in DD with mood disorders.
Recommendations
l Alcohol and MDD
u First choice: mirtazapine, add-on naltrexone or alone, add-on naltrexone to
sertraline.
u Second choice: add-on disulfiram
u Third choice: Valproic acid, amitriptyline, imipramine, escitalopram
l Alcohol with Bipolar disorder
u First choice: Add-on naltrexone
u Second choice: add-on lamotrigine or alone, add-on valproic acid or alone, add-
on disulfiram
u Third choice: add-on gabapentin, add-on topiramate, lithium
l Cannabis with Bipolar disorder

u First choice: add-on valproic acid to lithium

u Second choice: Lithium, add-on valproic acid
l Cocaine with MDD
u Add-on risperidone or alone
l Cocaine with Bipolar disorder
u First choice: add-on valproic acid to lithium
u Second choice: add-on lamotrigine or alone, lithium, add-on valproic acid or
alone, add-on quetiapine or alone, add-on rispridone or alone
l Opioid SUD with MDD/Bipolar disorder:
u No evidence base recommendation is possible. However, treatment as usual for
the affective disorder is likely to be effective.
l Psychotherapy
u Major depressive disorder: Motivational interviewing and Contingency
management may be useful.
u Bipolar disorder: Motivational interviewing and Contingency management may
be useful.
3.4 Anxiety Disorders
Anxiety disorders and SUD are commonly comorbid.88 This has been borne out in all
large scale epidemiological surveys.30 The presence of this comorbidity is predictive of
poor prognosis and recovery from either condition.89 Generalized anxiety disorder and
panic disorder were found to have the highest comorbidity with SUD.90 The pattern of
these comorbidities has been confirmed in a recent review.91 As with mood disorders,
the evidence base for interventions in DD with anxiety disorders is meagre. As far as the
authors are aware, no treatment guidelines explicitly exist for this indication. However,
there is a recent review in this area.92
As anxiety symptoms are commonly associated with substance use, withdrawal and
MDD, a careful diagnostic exercise to confirm comorbidity is essential (level 4).92 This is
often difficult.
The evidence base for use of pharmacotherapy alone in this group of DD is sparse. A
category II study that investigated the use of paroxetine in subjects with alcohol
dependence and social anxiety disorder found improvement in anxiety but not so much
in alcohol quantity or frequency.93 In another category I b study of paroxetine in subjects
with similar pathology, somewhat similar results were seen.94 Another category I b study

with sertraline or placebo in alcohol SUD and posttraumatic stress disorder (PTSD) was
equivocal.95 There are studies that have investigated the possible utility of buspirone. A
category II a study in subjects with generalized anxiety disorder (GAD) and alcohol
SUD showed that buspirone was useful in measures of anxiety and drinking.96 A couple
of studies with buspirone in subjects with alcohol SUD and GAD, and subjects with
opioid dependence on methadone found no significant improvements in substance or
anxiety outcome parameters.97,98
The use of benzodiazepines in this group of patients is controversial. Whereas a
common sense approach would indicate that such agents should be used with
circumspection, actual data is sparse. Some studies suggest that those with SUD are
more prone to abusing and developing dependence to benzodiazepines.99 However
there are some studies to the contrary as well which suggest that with careful monitoring
and selection, benzodiazepines can be gainfully used in patients with SUD and anxiety
disorders.100,101
While there is ample evidence for the use of non-pharmacological therapies in the form
of behaviour therapies (BT) in anxiety disorders, the evidence base for the use of BT in
DD is mixed. A category III study showed that subjects with panic disorder with and
without agoraphobia and SUD had worse outcomes than those without when subjected
to CBT.102 Similarly, a category IIa study investigating the use of CBT in patients with
panic disorder and alcohol SUD found that CBT performed no better than treatment as
usual.103 Another category Ib study investigating the role of CBT in patients with alcohol
SUD and comorbid anxiety disorders showed that while CBT was effective in improving
anxiety outcomes, alcohol outcomes were not significantly different.104 Another
category Ib study showed that evidence based psychotherapy for PTSD in patients with
alcohol SUD did not perform better than supportive counselling and
pharmacotherapy.105 On the other hand, studies have shown that subjects with various
anxiety disorders and alcohol SUD respond equally well when compared to those
without alcohol SUD when subjected to various forms of BT.106-108 However these
studies were not as robust as the former.
Another interesting development is the testing of integrated treatments designed
specifically for comorbid anxiety disorders and SUD. These include the following. An
integrated CBT protocol for alcohol SUD and panic disorder has been developed.109 A
category 1b trial showed that integrated treatment was associated with reductions in
anxiety and alcohol use.110 Other integrated therapies have been devised for PTSD
comorbid with alcohol SUD. Therapies devised in this population group are seeking
safety111, integrated CBT112 and COPE (concurrent treatment of PTSD and substance use
disorders using prolonged exposure).113 Evidence base suggests that these treatments are

well tolerated and do not worsen PTSD symptoms.92 However, much more research
evidence is needed before these therapies enter the mainstream. The issue of paucity of
trained personnel to deliver these therapies in a country such as India is also pertinent.
Recommendations
l Given the association of anxiety symptoms and different phases of substance use, a
proper diagnostic exercise is essential before making a diagnosis of DD.
l Selective serotonin reuptake inhibitors may be useful in anxiety disorders with SUD.
l Benzodiazepines should be used with caution but should not be withheld when
indicated.
l Non-pharmacological methods of treatment in form of integrated, specific behaviour
therapies are recommended.
3.5 Personality disorders (PD)
PD, specially the antisocial personality disorder are commonly comorbid with
substance abuse.2 Similar findings have been reported for borderline personality
disorder as well.114 People with SUD are found to have a higher prevalence of PD than
the general population and the comorbidity of these conditions is associated with
greater impairment.114 While the comorbidity of PD and SUD is beyond doubt, there are
very few well-designed studies that have specifically looked at treatment protocols for
the same. Most studies concern with treatment strategies for individuals with PD where
some members of the population have SUD. Therefore, most guidelines in this section
are extrapolated rather than from direct evidence. There are some well-regarded
Cochrane reviews of management strategies for borderline and antisocial PD.115-119 The
British Association of Psychopharmacology has also issued updated guidelines on
treatment options for substance abuse and comorbidities that includes PD.120 Health
Canada also has a section on management options for the treatment of this DD.121 There
is a recent review on the treatment considerations in DD with borderline PD.122
It is a commonly held notion that people with PD do not respond well to treatment
strategies for SUD. However, this has been refuted and it has been suggested that people
with PD and SUD can benefit as much as people without this comorbidity to standard
treatments for SUD.123 There is some evidence to suggest that this is the case across
different PD, SUD and outcomes120 (level 4 evidence). These outcomes include
measures of substance abuse, high-risk behaviours, overall mortality and suicidality.
However, evidence also suggests that treatment for this DD does not improve the
symptoms of the PD per se and that such patients should also have dedicated treatment
for the PD120 (level 4 evidence). Whether any particular treatment modality is
specifically useful for both the SUD and the PD simultaneously is uncertain. There is

some evidence to suggest that successful treatment of SUD in patient with this DD may
predict improvement in the PD.124
As with other disorders, it is essential to make a proper diagnostic assessment. However,
screening instruments for PD are not easily available. Diagnosis would mostly require a
proper clinical interview and to gather as much information from as many informants as
possible (Level 4 evidence). Issues of anger and impulse control are often clues to the
presence of PD. As in other DD, concurrent, integrated treatment is the best choice for
this DD121 (level 4 evidence).
3.5.2 Borderline Personality Disorder
The 5 evidence base for treatment options in borderline PD and SUD DD is scant.
Psychotherapy: Dialectical behaviour therapy (DBT) has some evidence base in this
population. There are a couple of RCTs that have examined DBT in this population with
significant results125,126 (Level Ib evidence). In addition, there is one study of dynamic
deconstructive psychotherapy in this population.127
Pharmacotherapy: There is some evidence to suggest that disulfiram and naltrexone can
be used in patients with borderline and antisocial PD and alcohol SUD128 (Class Ib
evidence).
3.5.3 Antisocial Personality Disorder
The evidence base for treatment options in antisocial PD and SUD DD is scant.
Psychotherapy: there is some evidence (Level IIb) regarding the usefulness of
contingency management in abstinence from substance use in patients with cocaine
SUD.129 A similar study found that structured behavioural approach improved
behavioural measures but not necessarily substance related measures in patients with
opioid SUD (level Ib evidence).130
Pharmacotherapy: In double blind placebo controlled study, nortriptyline was found to
be useful in patients with antisocial PD and alcohol SUD.131 Desipramine was found to
be inferior to placebo in patients with cocaine SUD and antisocial PD.132
Recommendations
l The evidence base in this area is scanty.
l Interventions for SUD in patients without PD are likely to be as effective in patients
with PD.
l Successful treatment of SUD may benefit symptoms of PD.
l Dialectical behaviour therapy can be recommended in borderline PD with SUD.
l Contingency management can be recommended in antisocial PD with SUD.

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The Clinical Practice Guidelines for the Assessment and Management of
Substance Use Disorders (CPG-SUD) was prepared by the Indian Psychiatric
Society Specialty Section on Substance Use Disorders and published by IPS in
January 2014. The following year, in January 2015, a more concise, practice-
oriented, easy-to-carry and easy-to-follow supplementary companion of the
comprehensive CPG-SUD book was published (“The Synopsis”). Since their
publication, both the CPG-SUD and its Synopsis books have been well received
by clinical practitioners, researchers, academicians, and psychiatric students,
i.e., by all the target groups these books were meant for.
However, the scenario of addictive disorders is never a static one. It witnesses
continual kaleidoscopic changes, with newer substances, newer patterns, and
indeed, newer 'addictions' emerging all the time. Four broad changes have been
noted in the landscape of addictive disorders in India of late. These are:
(a) Emergence of a heterogeneous group of various substances clubbed under
the term “New Psychoactive Substances (NPS)”, which evade the existing
regulatory legal framework but nonetheless, can be harmful;
(b) Emergence of long-known but so far less used substances in India in an
emergent manner (such as cocaine and amphetamine-type stimulants), often
in the context of rave parties or similar gatherings (the so-called “club
drugs”);
(c) Recent recognition of patterns of maladaptive behavioural excess involving
particular behaviours (gambling, use of technology like computer and
Internet, eating, sexual activities, etc.), which do NOT primarily involve use
of psychoactive substances as such (known as “behavioural addictions”);
and finally,
(d) Enhanced probability of clinically encountering various combinations of
substance use disorders with non-substance psychiatric disorders (known as
dual diagnosis or dual disorders).
Thus, this year, the Specialty Section decided to focus on “Newer and Emerging
Addictive disorders in India”.
CPGs are meant to inform, assist and “guide” the clinician, not to ask them to
sacrifice their autonomy of clinical judgment, nor to be oblivious of the
individual patient's clinical situation and psychosocial context. With this
disclaimer and caveat, however, we believe that this new set of the CPGs, when
properly used along with clinical training in addiction psychiatry, can be a very
useful and handy companion to the students, clinicians and even teachers in
their day-to-day practice.
Debasish Basu, P.K. Dalal, Y.P.S. Balhara (Editors)

MM

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CLINICAL PRACTICE GUIDELINES

on Newer and Emerging

Indian Psychiatric Society

Indian Psychiatric Society

An Official Publication of Indian Psychiatric Society

© All rights reserved.

Executive Council Members (Direct)

INDIAN PSYCHIATRIC SOCIETY

IPS PUBLICATION COMMITTEE

Yatan Pal Singh Balhara

Shubh Mohan Singh

Dr. Gautam Saha Dr. Sandeep Shah

CLINICAL PRACTICE GUIDELINES ON

© Indian Psychiatric Society 2016 5

Need for the current volume of CPG

6 © Indian Psychiatric Society 2016

© Indian Psychiatric Society 2016 7

8 © Indian Psychiatric Society 2016

While not always possible or feasible, we have attempted to maintain a degree of

© Indian Psychiatric Society 2016 9

10 © Indian Psychiatric Society 2016

AGREE II Item CPGs of IPS-SS-SUD 2016

© Indian Psychiatric Society 2016 11

AGREE II Item CPGs of IPS-SS-SUD 2016

Appendix 2. Categories of Evidence and Strength of Recommendations

IV : evidence from expert committee reports or opinions and/or clinical experience of

© Indian Psychiatric Society 2016 13

© Indian Psychiatric Society 2016 17

include gambling, gaming, Internet addiction, food addiction, sex addiction,

18 © Indian Psychiatric Society 2016

3.1 Behavioural Addictions

© Indian Psychiatric Society 2016 19

the conflict associated with such behaviour.

20 © Indian Psychiatric Society 2016

Knowledge Competencies Training and Resource Mobilisation

Relevant Investigations Use of appropriate Support for trained human resource

Pharmacology and Symptomatic and specific Funding support for research on

© Indian Psychiatric Society 2016 21

Knowledge Competencies Training and Resource Mobilisation

22 © Indian Psychiatric Society 2016

© Indian Psychiatric Society 2016 23

compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson

24 © Indian Psychiatric Society 2016

NEWER AND EMERGING SUBSTANCES

© Indian Psychiatric Society 2016 29

© Indian Psychiatric Society 2016 31

32 © Indian Psychiatric Society 2016

© Indian Psychiatric Society 2016 33

Panel 1: Classification of New Psychoactive Substances (NPS) by UNODC4

34 © Indian Psychiatric Society 2016

2. SCOPE AND METHODOLOGY OF THE GUIDELINE

© Indian Psychiatric Society 2016 35

36 © Indian Psychiatric Society 2016

Panel 2: Profile of individual with New Psychoactive Substance (NPS) use

4. ASSESMENT OF SUSPECTED CASES OF NPS INTOXICATION

© Indian Psychiatric Society 2016 37

Head & neck Conjunctival injection Synthetic cannabinoids Recent use

38 © Indian Psychiatric Society 2016

Body systems Physical findings/ Suspected NPS Association with

Panel 3: When to suspect New Psychoactive substance (NPS) toxicity?

4.2 Laboratory assessment

© Indian Psychiatric Society 2016 39

spectrometry (LC-MS/MS) screening procedure for NPS in blood. Simultaneous