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Amphetamine-Related Psychiatric Disorders

Updated: Sep 12, 2017
Author: Amy Barnhorst, MD; Chief Editor: Glen L Xiong, MD

Overview
Background
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) describes the
following 11 amphetamine-related psychiatric disorders:[1]

1. Amphetamine-induced anxiety disorder

2. Amphetamine-induced bipolar disorder
3. Amphetamine-induced depressive disorder
4. Amphetamine-induced psychotic disorder
5. Amphetamine-induced sexual dysfunction
6. Amphetamine-induced sleep disorder
7. Amphetamine intoxication
8. Amphetamine intoxication delirium
9. Amphetamine withdrawal
10. Amphetamine-induced obsessive-compulsive and related disorder
11. Unspecified stimulant-related disorder

Either prescription or illegally manufactured amphetamines can induce these disorders.

Prescription amphetamines are used frequently in children and adolescents to treat attention
deficit hyperactivity disorder (ADHD), and they are the most commonly prescribed medications
in children. The dose of Adderall(XR) (dextroamphetamine sulfate, dextroamphetamine
saccharate, amphetamine aspartate monohydrate, amphetamine sulfate) needed to produce
toxicity and psychiatric symptoms in a child is as low as 2 mg. A typical dose is 2.5-40 mg/d. In
adults, narcolepsy, ADHD of the adult type, and some depression can be treated with
amphetamines. Although they are controlled substances, abuse is possible, especially in persons
with alcoholism or substance abuse.

The substance 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational

stimulant commonly referred to as ecstasy, which was manufactured legally in the 1980s.[2]
MDMA has the desired effects of euphoria, high energy, and social disinhibition lasting 3-6
hours. The drug is often consumed in dance clubs, where users dance vigorously for long
periods. The drug sometimes causes toxicity and dehydration, as well as severe hyperthermia.
Several other amphetamine derivatives are para -methoxyamphetamine (PMA), 2,5-dimethoxy-
4-bromo-amphetamine (DOB), methamphetamine (crystal methamphetamine, crystal meth, or
"Tina"), and 3,4-methylenedioxyamphetamine (MDA). Crystal meth is the pure form of
methamphetamine, and, because of its low melting point, it can be injected.

In a web-based survey of 1,006 individuals who admitted mephedrone use, which is the largest
survey to-date, results showed that users consider mephedro’e's effects to compare best with
those of MDMA; the appeal of mephedrone for these individuals is in its availability, low price,
and reliable purity.[3]

Khat (Catha edulis Forsk) is the only known organically derived amphetamine. It is produced
from the leaves of the Qat tree located throughout East Africa and the Arabian Peninsula. The
leaves of the tree are chewed, extracting the active ingredient, cathinone, and producing the
desired effects of euphoria and, unlike other amphetamines, anesthesia.

In the midwestern United States, methcathinone, the synthetic form of cathinone, has been
produced illegally since 1989, after a student at the University of Michigan stole research
documents and began to illegally manufacture the drug. Methcathinone is relatively easy to
produce and contains the same chemicals found in over-the-counter (OTC) asthma and cold
medicines, paint solvents and thinners, and drain openers (eg, Drano). Its addiction potential is
similar to that of crack cocaine.

Amphetamine-related psychiatric disorders are conditions resulting from intoxication or long-

term use of amphetamines or amphetamine derivatives. Such disorders can also be experienced
during the withdrawal period from amphetamines. The disorders are often self-limiting after
cessation, though, in some patients, psychiatric symptoms may last several weeks after
discontinuation. Some individuals experience paranoia during withdrawal as well as during
sustained use. Amphetamine use may elicit or be associated with the recurrence of other
psychiatric disorders. People addicted to amphetamines sometimes decrease their use after
experiencing paranoia and auditory and visual hallucinations. Furthermore, amphetamines can be
psychologically but not physically addictive.

The symptoms of amphetamine-induced psychiatric disorders can be differentiated from those of

related primary psychiatric disorders by time. If symptoms do not resolve within 2 weeks after
the amphetamines are discontinued, a primary psychiatric disorder should be suspected.
Depending on the severity of symptoms, symptomatic treatment can be delayed to clarify the
etiology.

Amphetamine-induced psychosis (delusions and hallucinations) can be differentiated from

psychotic disorders when symptoms resolve after amphetamines are discontinued. Absence of
first-rank Schneiderian symptoms, including anhedonia, avolition, amotivation, and flat affect,
further suggests amphetamine-induced psychosis. Symptoms of amphetamine use may be
indistinguishable from those associated with the cocaine use. Amphetamines, unlike cocaine, do
not cause local anesthesia and have a longer psychoactive duration.

Amphetamine-induced delirium follows a reversible course similar to other causes of delirium,

and it is identified by its relationship to amphetamine intoxication. After the delirium subsides,
little to no impairment is observed. Delirium is not a condition observed during amphetamine
withdrawal.

Mood disorders similar to hypomania and mania can be elicited during intoxication with
amphetamines. Depression can occur during withdrawal, and repeated use of amphetamines can
produce antidepressant-resistant amphetamine-induced depression. Of interest, low-dose
amphetamines can be used as an adjunct in the treatment of depression, especially in patients
with medical compromise, lethargy, hypersomnia, low energy, or decreased attention.

Sleep disturbances appear in a fashion similar to mood disorders. During intoxication, sleep can
be decreased markedly. In withdrawal, sleep often increases. A disrupted circadian rhythm can
result from late or high doses of prescription amphetamines or from chronic or intermittent abuse
of amphetamines. Individuals who use prescription amphetamines can easily correct their sleep
disturbance by lowering the dose or taking their medication earlier in the day than they have
been. Insomnia is the most common adverse effect of prescription amphetamines.

Unspecified stimulant-related disorder is a diagnosis assigned to those who have several

psychiatric symptoms associated with amphetamine use but who do not meet the criteria for a
specific amphetamine-related psychiatric disorder.

Case study

A 36-year-old white male who works as a real estate agent arrives at your office, depressed,
disheveled, and slightly agitated. He is very guarded and reluctant to talk about his work history
or relationships. After a period of time he describes how his coworkers are manipulating his
clock to read 9:11, and the police drive by with their sirens on every day at 4:20. He refuses to
open his mail, because he read secondary messages by rearranging letters. He admits to spending
most of his time at home alone fixing his computer, sometimes all night long. His sleep cycle is
reversed on the weekends, he is depressed most of the time, isolated, lost 25 lbs in the last 3
months, and has pale skin. Only when asked about the burn mark on his hand did he admit to
"smoking some T." On further questioning he disclosed a 5-month period of crystal
methamphetamine use.

Pathophysiology
The pathophysiology of amphetamine-related psychiatric disorders is difficult to establish,
because amphetamines influence multiple neural systems. In general, chronic amphetamine
abuse may cause psychiatric symptoms due to inhibition of the dopamine transporter in the
striatum and nucleus accumbens. The longer the duration of use, the greater the magnitude of
dopamine reduction. Methamphetamine has been suggested to induce psychosis through
inhibiting the dopamine transporter, with a resultant increase in dopamine in the synaptic
cleft.[4]

Amphetamine-induced psychosis often results after increased or large use of amphetamines, as

observed in binge use or after protracted use. Prescription amphetamines induce the release of
dopamine in a dose-dependent manner; low doses of amphetamines deplete large storage
vesicles, and high doses deplete small storage vesicles. This increase in dopaminergic activity
may be causally related to psychotic symptoms because the use of D2-blocking agents (eg,
haloperidol) often ameliorates these symptoms. Amphetamine-induced psychosis has been used
as a model to support the dopamine hypothesis of schizophrenia, in which overactivity of
dopamine in the limbic system and striatum is associated with psychosis. However, negative
symptoms commonly observed in schizophrenia are relatively rare in amphetamine psychosis.

MDMA causes the acute release of serotonin and dopamine and inhibits the reuptake of
serotonin into the neuron. MDMA has neurotoxic properties in animals and, potentially, in
humans. Reports suggest that MDMA use is associated with cognitive, neurologic, and
behavioral abnormalities, as well as hyperthermia, but these reports are confounded by the
association with other factors (eg, heat, exertion, poor diet, other drug use). Serotonergic damage
has been suggested to lead to cognitive impairment.

Delirium caused by amphetamines may be related to the anticholinergic activity, as observed in

different classes of drugs, such as tricyclic antidepressants, benzodiazepines, sedatives, and
dopamine-activating drugs. Rapid eye movement during the first phase is decreased during
intoxication, and a rebound elevation of rapid eye movement occurs during withdrawal; this
effect eventually alters the circadian rhythm and results in sleep disturbances.

Epidemiology
Frequency

United States

Psychosis, delirium, mood symptoms, anxiety, insomnia, and sexual dysfunction are considered
rare adverse effects of therapeutic doses of prescription amphetamines. Dextroamphetamine has
a slightly increased rate of these adverse effects because of its increased CNS stimulation.

Data about the frequency of amphetamine-related psychiatric disorders are unreliable because of
comorbid primary psychiatric illnesses.

Intravenous (IV) use occurs more frequently in people of low socioeconomic status than in those
of high socioeconomic status.

The rates for past month use of methamphetamine did not change from 2011 to 2013, remaining
at approximately 0.2%. However, this does represent a nearly two-fold increase from the
percentage of the population surveyed who had used in the last month in 2010 (0.1%). In 2013,
an estimated 144,000 people became new users of methamphetamine, which is consistent with
the new user initation rates of the preceding five years.[5]

Post-marketing studies of amphetamines prescribed to children and adolescents revealed a total

of 865 unique case reports describing signs and/or symptoms of psychosis or mania, with nearly
half reported in children 10 years or younger.[6]
International

The first amphetamine epidemic occurred after World War II in Japan, when leftover supplies
intended to counteract fatigue in pilots were made available to the general public. This even
resulted in many cases of amphetamine psychosis. Of interest, both German and American
troops used these preparations during World War II, as did Japanese kamikaze pilots.

Khat, which is primarily used in Ethiopia for cultural and religious purposes, has been well
studied. A house-to-house survey of 10,468 adults showed a lifetime prevalence of khat use of
55.7%. Daily use occurred among 17.4%, and 80% indicated they used khat to increase
concentration during prayer.[7] Khat dependency has been associated with people of Muslim
religion and with people of low socioeconomic status.

Khat is also used to cope with the trauma of war in Somalia. One study showed that 36.4% of
Somali combatants used khat 1 week prior to being interviewed.

Mortality/Morbidity

The Drug Abuse Warning Network (DAWN) Annual Medical Examiner Data for 2005 showed
10% of all drug-related hospital emergency department visits were stimulant-related. DAWN
data indicated that 26% of all drug-related deaths in Oklahoma City were due to
methamphetamine, making it the city's most frequent drug-related cause of death in 1998.

In high doses, prescription amphetamines can produce cardiovascular collapse, myocardial

infarction, stroke, seizures, renal failure, ischemic colitis, and hepatotoxicity. Death related to
MDMA can occur from malignant hyperthermia, which leads to kidney failure and
cardiovascular collapse. Heart attacks, seizures, subarachnoid and intracranial hemorrhage, and
strokes may also result in death. The rate of suicide and accidents can increase during periods of
toxicity and withdrawal.

In high doses, prescription amphetamines and amphetamine derivatives increase sexual arousal
and disinhibition, increasing the risk of exposure to sexually transmitted diseases.

Memory impairment can result after long-term use of high doses of amphetamines because of
damage to serotonin-releasing neurons. In the emergency department patients with
amphetamine-related disorders are one third more likely than patients with cocaine-related
disorders to be transferred to an inpatient psychiatric ward. This difference may partly be
because amphetamine withdrawal lasts longer then cocaine withdrawal, and amphetamines are
more psychogenic than cocaine.

Amphetamine withdrawal is consistent with a major depressive episode, though lasting less then
2 weeks and involving decreased energy, increased appetite, craving for sleep, and suicidal
ideation.

Race-, sex-, and age-related demographics

Amphetamine-related psychiatric disorders most commonly occur in white individuals.

With IV use, amphetamine-related psychiatric disorders most commonly occur in men, with a
male-to-female ratio of 3-4:1. With non-IV use, amphetamine-related psychiatric disorders occur
equally in men and women.

Amphetamine-related psychiatric disorders most frequently occur in people aged 20-39 years
who are inclined to abuse amphetamine derivatives at rave parties and dance clubs.

Adolescents have developed a method for abusing prescription amphetamines in which

prescription tablets are crushed into a powder and inhaled nasally.

Presentation
History
Amphetamine-related psychiatric disorders can be confused with psychiatric disorders caused by
organic, medical, neurologic, and/or psychological etiologies. The causes of amphetamine-
related psychiatric disorders usually can be determined by assessing the patient's history and the
family's genealogy.

The DSM-5 provides criteria helpful for determining if the patient is in a state of intoxication or
withdrawal. The criteria helps clinicians distinguish disorders occurring during intoxication (eg,
psychosis, delirium, mania, anxiety, insomnia) from those occurring during withdrawal (eg,
depression, hypersomnia).

Developmental history

The developmental history provides information about the patient's in utero exposure to
medications, illicit drugs, alcohol, pathogens, and trauma.

As children, patients may have had prodromal symptoms of psychiatric disorders, such as social
isolation, deteriorating school performance, mood liability, amotivation, avolition, anhedonia,
sleep disturbances, sexual paraphilias, poor interest, psychomotor retardation, demoralization,
social isolation, and suicidal thoughts and behaviors.

Delinquency, truancy, educational failure, early use of drugs and alcohol, oppositional behavior
associated with conduct disorder, and participation in the rave party scene are developmental
behaviors that suggest an amphetamine-related psychiatric disorder.

Psychiatric history

Two issues are emphasized:

  Determine whether a psychiatric disorder or symptoms ever occurred when the patient
was not exposed to amphetamines.
 Determine whether the patient ever had a psychiatric disorder or symptoms similar to the
present symptoms in relation to any other drug or medication.

Recent history

The patient's history of amphetamine abuse is the most important factor and is determined by
asking the following questions:

 When did the patient's amphetamine use start?

 How often does the patient use amphetamines?
 How much does he or she use?
 Is the patient currently intoxicated or in withdrawal from amphetamines?
 Does the patient frequently attend rave parties?
 Has the patient recently increased his or her amphetamine use or started to binge?

Substance abuse history

Potentially abused substances include the following:

 Alcohol
 Marijuana
 Cocaine
 Lysergic acid diethylamide (LSD)
 OTC sympathomimetics
 Steroids

Family history

A family history of a psychiatric disorder may suggest a primary psychiatric disorder. A

diagnosis of amphetamine-related psychiatric disorder might still be possible if the patient has no
family history of psychiatric disorder.

DSM criteria for intoxication and withdrawal

The DSM-5 criteria for stimulant intoxication are as follows:

 A. Recent ues of an amphetamine-type substance, cocaine or other stimulant.

 B. Clinically significant problematic behavioral or psychological changes (e.g., euphoria
or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity;
anxiety, tension, or anger; stereotyped behaviors; impaired judgment) that develop
during, or shortly after, use of a stimulant.
 C. Two (or more) of the following signs or symptoms, developing during, or shortly after,
stimulant use:
o Tachycardia or bradycardia
 o Pupillary dilatation
o Elevated or lowered blood pressure
o Perspiration or chills
o Nausea or vomiting
o Evidence of weight loss
o Psychomotor agitation or retardation
o Muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias
o Confusion, seizures, dyskinesias, dystonias, or coma
 The signs or symptoms are not attributable to another medical condition, and are not
better explained by another mental disorder, including intoxication with
another substance.

The DSM-5 criteria for stimulant withdrawal are as follows:

 A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine, or

other stimulant use.
 B. Dysphoric mood and two (or more) of the following physiologic changes developing
within a few hours to several days after Criterion A:
o Fatigue
o Vivid, unpleasant dreams
o Insomnia or hypersomnia
o Increased appetite
o Psychomotor retardation or agitation
 The signs or symptoms in Criterion B cause clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
 The signs or symptoms are not attributable to another general medical condition, and are
not better explained by another mental disorder, including intoxication or withdrawal
from another substance.

Physical
Full physical and neurologic examination should be performed. Initially assess patients for
medical stability and then for level of danger.

During physical examination, assess the patient for medical complications of amphetamine
abuse, including hyperthermia, dehydration, renal failure, and cardiac complications.

During neurologic examination, assess the patient for neurologic complications of amphetamine
abuse, including subarachnoid and intracranial hemorrhage, delirium, and seizures.

Mental status examination should emphasize delusions, hallucinations, suicide, homicide,

orientation, insight and judgment, and affect. The mental status examination can be very
different for intoxication and psychosis.

A mental status expected for a patient with amphetamine intoxication is as follows:

  Appearance and behavior: Unusually friendly, scattered eye contact, buccal oral
gyrations, excoriations on extremities and face from picking at skin, overly talkative and
verbally intrusive[8]
 Speech: Increased rate
 Thought process: Tangential, circumstantial over inclusive and disinhibited
 Thought content: Paranoid; no suicidal or homicidal thoughts
 Mood: Anxious, hypomanic
 Affect: Anxious and tense
 Insight and judgment: Poor
 Orientation: Alert to person, place, and purpose; perspective of time is disorganized

A mental status expected for a patient with amphetamine psychosis is as follows:[9, 10]

 Appearance and behavior: Disheveled, suspicious, paranoid, difficult to engage, and poor
eye contact
 Speech: Decreased and rapid
 Thought process: Guarded and internally preoccupied
 Thought content: Paranoid; possible auditory hallucinations; no suicidal or homicidal
thoughts
 Mood: Anxious
 Affect: Paranoid and fearful
 Insight and judgment: Poor
 Orientation: Has no concept of purpose, though understands place and person;
perspective of time is disorganized.

A mental status for a patient withdrawing form amphetamines is as follows:

 Appearance and behavior: Disheveled, psychomotor slowing, poor eye contact, pale
appearance to skin
 Speech: Decreased tone and volume
 Thought processes: Decreased content, guarded
 Thought content: No auditory, visual hallucinations; suicidal thoughts present, but no
homicidal thoughts
 Mood: depressed
 Affect: Flat and withdrawn
 Insight and judgment: Poor
 Orientation: Oriented to person, place, and purpose

Causes
Causes may include the following:

 Amphetamine intoxication, binge pattern use, and long-term exposure

 Comorbid psychiatric disorders, such as depression, psychotic disorders, and anxiety
disorders
 Abuse of other substances such as alcohol, OTC sympathomimetics, and illicit drugs
  Dehydration, which can result in electrolyte imbalances and renal failure
 Potential for serotonin syndrome in those prescribed serotonin reuptake inhibitors or
serotonin norepinephrine reuptake inhibitors

DDx
Differential Diagnoses
 Cannabis-Related Disorders
 Cocaine-Related Psychiatric Disorders
 Delirium
 Depression
 Hallucinogen Use
 Hyperthyroidism and Thyrotoxicosis
 Hypothyroidism
 Inhalant-Related Psychiatric Disorders
 Insomnia
 Opioid Abuse
 Phencyclidine (PCP)-Related Psychiatric Disorders
 Schizophrenia
 Toxicity, Heroin
 Toxicity, Mushroom
 Wernicke-Korsakoff Syndrome

Workup

Workup
Laboratory Studies
The purpose of the workup is to exclude complications of amphetamine abuse and other causes
of psychosis and altered mental status.

Laboratory evaluation should include the following tests:

 Finger-stick blood glucose test

 CBC determination
 Determination of electrolyte levels, including magnesium, amylase, albumin, total
protein, uric acid, BUN, alkaline phosphatase, and bilirubin levels
 Urinalysis
  Stat urine or serum toxicology screening to exclude acetaminophen, tricyclic
antidepressants, aspirin, and other potential toxins: Individuals who abuse drugs may
ingest a substance called Urine Luck, or pyridinium chlorochromate (PCC), to produce
invalid results on urine drug screens. PCC alters the results for cannabis and opiates but
elevates levels of amphetamines.
 Blood test for an alcohol level if the patient appears intoxicated
 HIV and rapid plasma reagin (RPR) tests

Imaging Studies
In the presence of neurologic impairments, CT or MRI helps in evaluating for subarachnoid and
intracranial hemorrhage.

Other Tests
Perform ECG to evaluate for cardiac involvement.

Perform EEG if a seizure disorder is considered possible.

Use of the brief psychotic rating scale (BPRS), Beck Depression Scale, violence and suicide
assessment, and other measures may be helpful.

If persistent psychiatric conditions are noted, neuropsychological testing can be beneficial to

assess levels of psychosocial and neurologic function to guide treatment and to assess the need
for placement.

Results of projective testing, such as the Rorschach test and the Thematic Apperception Test, can
help in clarifying thought disorders.

During amphetamine intoxication, the Mini-Mental State Examination (MMSE) can be helpful in
measuring cognitive change.

Histologic Findings
Repeated exposure to amphetamines is theorized to alter the morphology of dendrites in the
prefrontal cortex and in the nucleus accumbens. Amphetamines may increase the length of
dendrites for longer than 1 month. These alterations may help explain the behavioral cravings
and psychosis that long-term abuse of amphetamines produces.

Treatment
Medical Care
Initial treatment should include medically stabilizing the patient's condition by assessing his or
her respiratory, circulatory, and neurologic systems. The offending substance may be eliminated
by means of gastric lavage and acidification of the urine. Psychotropic medication can be used to
stabilize an agitated patient with psychosis. Because most cases of amphetamine-related
psychiatric disorders are self-limiting, removal of the amphetamines should suffice.

Induced emesis, lavage, or charcoal may be helpful in the event of overdose.

The excretion of amphetamines can be accelerated by the use of ammonium chloride, given
either IV or orally (PO).

 Amphetamine intoxication can be treated with ammonium chloride, often found in OTC
expectorants, such as ammonium chloride (Quelidrine), baby cough syrup, Romilar, and
P-V-Tussin.
 The recommended dose to acidify the urine is ammonium chloride 500 mg every 2-3
hours.
 The ingredients in OTC cough syrups vary, and the clinician should become familiar with
1 or 2 stock items for use in the emergency department.
 Ammonium chloride (Quelidrine), an OTC expectorant, can be used in the absence of
liver or kidney failure.
 Administer IV fluids to provide adequate hydration.
 If the patient is psychotic or if he or she is in danger of harming him or herself or others,
a high-potency antipsychotic, such as haloperidol (Haldol), can be used. Exercise caution
because of the potential for extrapyramidal symptoms, such as acute dystonic reactions,
and neuroleptic malignant syndrome.
 Agitation also can be treated cautiously with benzodiazepines PO, IV, or intramuscularly
(IM). Lorazepam (Ativan) and chlordiazepoxide (Librium) are commonly used.
 Administer naloxone (Narcan) in the event of concurrent opiate toxicity. Use caution to
avoid precipitation of acute opioid withdrawal in a patient who has used high doses of
opioid on a long-term basis.
 Beta-blockers, such as propranolol (Inderal), can be used in the event of elevated blood
pressure and pulse. They also may be helpful with anxiety or panic.
 Psychiatric hospitalization may be necessary when psychosis, aggression, and suicidality
cannot be controlled in a less restrictive environment.
 If serotonin syndrome is suspected, stop all SSRI and SNRI medications.

Consultations
Consultations with a neurologist, internal medicine specialist, psychiatrist, or social services may
prove helpful.

Consult a psychiatrist for inpatient substance abuse treatment or further psychiatric stabilization.

Social services coordinate outpatient services, such as Alcoholics Anonymous and Narcotics
Anonymous meetings and sober houses, and provide appointments. Some large metropolitan
areas have groups that specifically focus on crystal methamphetamine abuse in the gay
population.

Activity
Patients intoxicated with amphetamines are dangerous, and their activity should be limited (eg,
no driving) until their symptoms have resolved.

Medication
Medication Summary
Several psychiatric conditions can be associated with amphetamine intoxication and withdrawal,
all of which may require different management strategies. However, amphetamine-related
psychiatric disorders are typically self-limited and usually remit on their own.

Amphetamine-related psychiatric disorders occur most often during intoxication; therefore,

treatment should focus on controlling medical and psychiatric symptoms while eliminating the
offending substance. Medical therapy involves stabilizing agitation and minimizing psychosis.
Gastric lavage directly removes the amphetamines before they have an opportunity to be
absorbed. Medication and charcoal eliminate amphetamines from the gastrointestinal and
circulatory systems.

If the induced disorders persist and interfere with the patient's social and occupational
functioning, treatment should be related to the remaining psychiatric symptoms. Antidepressants,
such as sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa), can
be used to treat depression. Antimanic agents, such as valproic acid (Depakote), carbamazepine
(Tegretol), and lithium carbonate, can be used to treat mania. Anxiety can be treated with
nonbenzodiazepine drugs, such as beta-blockers and antimanic agents.

Data from recent studies suggest typical antipsychotics (haloperidol thioridazine, Thorazine, etc)
may increase amphetamine and cocaine cravings in patients with dual diagnoses of amphetamine
and cocaine abuse. Typical antipsychotics should be used for acute stabilization with the
intention of switching to an atypical antipsychotic drug (eg, risperidone, quetiapine, olanzapine,
aripiprazole, and ziprasidone) for long-term use.

Some evidence suggests that naltrexone might be helpful in treating those addicted to
amphetamines.[11]

For the purposes of this discussion, specific treatment of amphetamine toxicity is reviewed. For
further information, please refer to the articles on Depression, Substance-Induced Mood
Disorder, Depressed Type, Bipolar Affective Disorder, Schizophrenia, Anxiety Disorders, and
Sleeping Disorders.
Antipsychotics
Class Summary

Clinicians should select a high-potency antipsychotic that is available in tablet, liquid, and IM
forms for administration in emergency situations. Antipsychotics help control psychotic
symptoms and provide rapid tranquilization of the agitated and psychotic patient.

Haloperidol (Haldol)

Provides rapid sedation of agitated anxious patient; available PO and IM, allowing for flexible,
emergency administration.

Thiothixene (Navane)

Blocks postsynaptic blockade of CNS dopamine receptors, inhibiting dopamine-mediated

effects. PO and IM forms allow for rapid tranquilization.

Benzodiazepines
Class Summary

These drugs are primarily used to sedate agitated patients. Availability in PO, IV, and IM forms
allowing the drug to be used in emergency situations. Caution must be used in the violent,
aggressive patient because benzodiazepines may cause disinhibition.

Lorazepam (Ativan)

Provides rapid onset and efficacy in sedating aggressive patient; flexible administration in
emergency situation.

Chlordiazepoxide (Librium, Libritabs, Mitran)

Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing
activity of gamma-aminobutyric acid (GABA) activity, major inhibitory neurotransmitter.

Opiate antagonists
Class Summary

These drugs inhibit the action of opiates.

Naloxone (Narcan)
Used to treat concurrent opiate toxicity. Consider in patients with altered mental status due to
opiate overdose. Poorly absorbed PO route and should be administered IM or IV. Available in
IV, IM, and SC forms. Use caution to avoid precipitating acute opioid withdrawal in patient
using opioids long term.

Beta-blockers
Class Summary

Propranolol (Inderal) is useful in patients who are agitated, anxious, and hyperarousable because
of amphetamines. They are temporarily used until the amphetamine is eliminated from the
patient's system. For some patients, anxiety can be prolonged, and nonaddictive beta-blockers
may be helpful.

Propranolol (Inderal)

Antihypertensive agent useful in psychiatry to treat anxiety and impulse control. Often well
tolerated with minimal effect on hemodynamics of blood pressure and pulse.

Expectorants
Class Summary

Expectorants are used to acidify the urine and increase amphetamine excretion when intoxication
from amphetamines has resulted in psychiatric and medical complications. These agents are
available in PO form, and the patient must be able to swallow or receive a nasogastric tube.

Ammonium chloride (Quelidrine)

Commonly used as OTC expectorant; acidifies urine at high doses. Safe and easy to use.

Adsorbents
Class Summary

These agents, given through a nasogastric tube into the stomach, absorb intentionally and
accidentally ingested substances to prevent their further absorption into the systemic circulation.

Activated charcoal suspension (Actidose-aqua, Inst-Aqua, Liquid-Char)

Bottles and tubes. Use long after amphetamine ingestion can reduce systemic levels by adsorbing
amphetamines recirculating through gastric mucosa.
Follow-up
Further Outpatient Care
The patient should be monitored closely for recurring psychosis, depression, mania, anxiety,
sleep disturbances, and relapse of amphetamine abuse.

Psychiatric follow-up care should occur within, at most, 2 weeks of the initial evaluation to
ensure compliance.

Depending on the complications of amphetamine abuse in the specific patient, consider a follow-
up examination with a neurologist and an internal medicine specialist.

Further Inpatient Care

Admit the patient for observation in the event of mania, severe depression, psychosis, delirium,
or if he or she is suicidal or homicidal.

A patient who is in a state of delirium should be placed in a quiet, cool (not cold), dimly lit (not
dark) room and, if uncontrollable, placed in restraints.

Inpatient & Outpatient Medications

If psychosis persists after the offending substance is eliminated, use of an atypical antipsychotic
(risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone) may be considered. No single
atypical antipsychotic has been proven to be more beneficial than the others in managing
prolonged amphetamine-induced psychosis.

Antimanic agents may be continued if mania persists longer than 2 weeks.

Antidepressants can be useful if depression persists for 2 weeks after withdrawal.

Antidepressants alone may not be as effective as other options in amphetamine-induced
depression due to neuronal damage. Medication regimens for treatment-resistant organic mood
disorders are the applicable approach.

If anxiety persists longer than 2 weeks, consider the use of nonbenzodiazepine drugs.
Medications such as beta-blockers, valproic acid, carbamazepine, or gabapentin have shown
promise in patients with substance abuse who also have anxiety.

Sleep medication may help patients adjust their circadian rhythm and can be used for
approximately 1-2 weeks. If sleep medication is required for long periods, a referral to a sleep
clinic is recommended.

Transfer
If psychiatric conditions persist, causing social and occupational impairment, inpatient treatment
may be required.

Medical or neurologic complications require treatment in an inpatient medical or neurologic unit.

Deterrence/Prevention
Abstinence prevents disorders and is the primary treatment.

Relapse prevention occurs though patient education, individual psychotherapy, appropriate

medical treatment of continuing psychiatric illness (eg, major depression, panic disorder), and
attendance at substance abuse meetings.

Mandatory weekly urine drug screens help prevent relapse or expose relapse early so that
aggressive treatment intervention can be pursued.

If psychiatric conditions arise during prescription amphetamine use for ADHD, lower doses may
be tried and/or nonamphetamine treatments can be pursued, such as bupropion (Wellbutrin),
desipramine, venlafaxine (Effexor), or clonidine. Please refer to the Attention Deficit
Hyperactivity Disorder article for a full discussion of treatment options.

Early medication treatments have been tried with desipramine and lithium[12] ; aripiprazole vs.
methylphenidate vs. placebo[13] ; bupropion[14] ; and naltrexone.[15]

The most recent published study at the time of this review assessed the efficacy of extended-
release methylphenidate. The intention-to-treat analysis failed to demonstrate statistical
difference between extended-release methylphenidate (n=40) compared with placebo (n=39).
The authors noted that the study was limited by significantly higher dropout rates in the placebo
arm.[16]

Currently, there are no medications that are routinely prescribed as standard-of-care or approved
by the FDA for the treatment of amphetamine use disorder.

Complications
Complications include an increased risk of the following:

 Psychosis
 Depression
 Anxiety disorder
 Sleep disturbance
 Memory impairment
 Medical complications
 Neurologic complications
 Abuse of another or several substances
  Psychosocial impairment
 Affect dysregulation and aggression[17]

If amphetamine abuse and amphetamine-related psychiatric disorders occur in the context of 1 or

more personality disorders, the amphetamine-related disorder is more difficult to successfully
treat than it is in other contexts.

Prognosis
The patient's prognosis depends on the severity of psychiatric impairment and on the medical
complications.

Overall, the prognosis is good if the patient abstains from drug use after the initial psychiatric
impairment occurs.

The prognosis worsens if personality disorders are present.

Patient Education
Instruct the patient to abstain from alcohol and illicit drugs, especially because dual diagnosis is
a real issue. The only effective treatment is abstinence.

Patients should be in a support group.

The family must be educated about the patient's addiction and its dangers.

Refer the patient for psychosocial counseling.

Hospitalize the patient if he or she is suicidal or homicidal.

Refer the patient for substance abuse counseling.

Helpful Web sites include the following

 Crystal Meth Anonymous

 National Institute on Drug Abuse, Methamphetamine Abuse and Addiction
 NIDA InfoFacts: Stimulant ADHD Medications - Methylphenidate and Amphetamines

For excellent patient and family education resources, see eMedicineHealth's patient education
articles Drug Dependence and Abuse and Substance Abuse.
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