Mania and ADHD

What should you know? Why should you care?

Gabrielle A. Carlson, MD
Professor of Psychiatry and Pediatrics Director, Child and Adolescent Psychiatry Stony Brook University School of Medicine Stony Brook, New York 631-632-8840

What ADHD is
ADHD is a heterogeneous, clinical condition If appropriately defined (with symptoms, pervasiveness and impairment) it may constitute a difference of degree and possibly kind from normal Deficit does not mean None. It means that attention cannot be sustained when the child or adult is not interested.

H-I-D-E (ADHD)
Developmentally inappropriate levels of: Hyperactivity (6/9 sx): fidgets with hands or feet or squirms in seat;
leaves seat in classroom inappropriately; runs about or climbs excessively; has difficulty playing quietly; is on the go or driven by a motor; talks excessively Impulsivity: blurts out answers before questions are completed; has difficulty awaiting turn; interrupts or intrudes on others Distractibility (6/9 sx): fails to give close attention to details; difficulty sustaining attention; does not seem to listen; does not follow through on instructions; difficulty organizing tasks or activities; avoids tasks requiring sustained mental effort; loses things necessary for tasks; easily distracted; forgetful in daily activities Emotionality (associated symptom): Low frustration tolerance; sensitive to criticism; over-reactive

Differentiation from normal

REMEMBER THE 3 Ps: Condition is PERSISTANT. It has gone on for at least 6 months It is PERVASIVE. More than one person observes it- present in different settings It is imPAIRING: interfering with childs functioning at home, with peers, with family, and/oror with his/her self- esteem or development.

Hyperkinetic Child SyndromeLaufer and Denhoff, 1957

SYMPTOM Hyperactivity Poor Concentration Variability Irritability/ Explosiveness Impulsiveness Sleep disturbance DESCRIPTOR Involuntary and constant overactivity that greatly surpasses normal Frequent shifting from one activity to another Behavior is unpredictable. "Sometimes he is good, sometimes bad" Fits of anger easily provoked ; reactions almost volcanic in intensity Does things on the spur of the moment. Cannot delay gratification Falls asleep at proper time but wakens after only a few hours "rampaging through the house in hyperactive, noisy, sleep-disturbing play" DSM IV ADHD YES YES NO NO YES NO

G. Carlson, 2009

Co-Occurring Disorders in MTA Children (n=579)

ADHD alone

31%
Tic 11% Dis. Dis . Conduct Disorder

Oppositional Defiant Disorder

40%

Mood Dis. Dis . 4% Anxiety 34% Disorder

14%

Course of the Disorder

Inattentio n
Though less than in childhood, it is still greater than In non-ADHD peers; verbal > physical

Less than in childhood; more often verbal and cognitive than non-AADHD same age peers

Age

Outcome of ADHD
"Developmental Delay" - about 30% outgrow the disorder by young adulthood (symptoms minimal; Ability to compensate)* milder disorder
"Continual Display" - about 40% remain symptomatic with functional impairment *Worse hyperactivity/inattention---> poor academics "Developmental Decay" - development of more serious antisocial and/or substance use disorders

* * * *

Irritable temperament----> AGGRESSION Worse executive function-------> WORSE IMPULSIVITY Worse social adjustment----> WORSE PEERS More family psychopathology---> higher gene load + Less involvement and poorer communication; high level of fighting/domestic violence; poor supervision and monitoring.

Ways to compare treatment

Statistical significance p<0.05 Effect size 0.8 or higher is strong 0.4-.7 is modest 0<.4 isnt very helpful especially if the problem is severe NNT (number needed to treat) and NNH (number needed to harm NNT should be low; NNH should be high

Meta-analysis of 29 controlled studies over 25 years, encompassing 4465 children, adolescents) with some added information (

Drug Amphetamine Methylphenidate Atomoxetine Guanfacine ER Clonidine Modafinil

Effect Size 0.92 0.80 0.73 0.73 0.58* 0.49

Bupropion Diet without additives

0.32 0.2

Faraone SV, Spencer TJ: Presented at: American Psychiatric Association Annual Meeting, Toronto, Canada, May 2006. * Connor et al., JAACAP, 1999

Effect of severity on ADHD

Mild
When obvious
Where it manifests Untreated outcome

Moderate
preschool
School -class and playground; Home-except computer Disorganization and defiance; worse in secondary school underachievement LD, ODD, anxiety,depression

Severe
Age <3
Everywhere and anywhere aggression; peer problems; drugs, underachievement LD, ODD/CD, other disorders

Elementary school
Unstimulating situations; homework time Worsens in secondary school underachievement Often uncomplicated

comorbidity

ADHD severity and treatment

Mild Educational Structure Moderate Classification; ? Severe SED classroom; Regular class interventions PRN tutoring sometimes hospitalization accommodations Home Structure; Behavior modification Behavior mod intervention behavior mod PRN needed Social and mental health rx medication If above strategies During school and for Many medication fail and child slips homework; +/trials; often academically and elsewhere depending combined behaviorally on impairment medications Therapy goals Psychoeducati on Organizational skills; self esteem help Psychoeducation Organizational skills; self esteem help Aggression, anger control Mood stabilization

MTA: % Normalized at 14 Months

100% 88%

80%

68% 56%

60%

40%

34%
25%

20%

0% Controls Comb MedMgt Beh CC

Comb = medical management + behavioral treatment; MedMgt = medical management; Beh = behavioral treatment; CC = community comparison group

Jensen PS, et al. J Dev Behav Pediatr. 2001;22:60-73.

Manic depression or rages?

= ?

Increase in BP Diagnosis in youth from nationally representative outpatient office visits

(Moreno et al., 2007)

% of all

For office-based visits with a mental disorder, rates went from .42% (n=25) in 1994 to 6.7% (n=1003)

Remember these acronyms

Mania: H*I*P*E*R*S

Hyperactivity (goal directed), Irritability, Psychosis (grandiosity), Elated/expansive mood, Rapid speech/Racing thoughts, Sleep (doesnt need it or want it) Definite personality change, Undeniable drop in grades, Morbid/suidical, Pessimistic, Somatic

Depression: D*U*M*P*S

Illness, drugs mania, called 2o Superimposed on other conditions Symptoms occur concurrently in episodes lasting at least a week for mania and 2 weeks for depression.

ADHD and Mania: Overlapping symptoms

Carlson & Meyer, ADHD with Mood Disorders, In Brown TE, ADHD Comorbidities: Handbook for ADHD Complications in Children and Adults, 2009

Case #1 Classic Bipolar I Disorder

Nicola -14+ years old; shy, nice , no behavior problems or substance abuse Age 10, brief depressive episode after Grandmas death; treated with psychotherapy; increased anxiety related to school demands in middle school. Several weeks before referral- parents said Nicolas personality had changed

wearing sexy clothes, talking to complete strangers, meeting boys on internet chat rooms; up all night; vulgar language.
Mood changes throughout the day from laughing hysterically, to being irritable, swearing and smashing things to becoming tearful and crying uncontrollably. Sleep patterns had changed; up late talking in chat rooms, sleep for a few hours but would wake early and rearrange room, waking the neighbours by usingGCarlson, the vacuum cleaner at 6 am. MD

Nicola continued Mental status: Nicola loud, intrusive, talked fast and laughed loudly. Hard to follow her train of thoughtshe rapidly changed the subject to seemingly unrelated topics. Convinced a TV actor whom she had been trying to contact, would call her and shed have a relationship with him. She used her cell phone to try to call him.

Became suspicious and hostile when asked about drug use which she adamantly denied; She would not allow the interviewer to see her parents alone, likewise, didnt want to be interviewed alone. She expressed a fear that her food may have been poisoned and that her brain had been damaged.
GCarlson, MD

Steve
8 year old, 3rd grade boy in regular education with explosive outbursts (throws chairs, sweeps stuff off of desks, attacks staff)

Chronically hyperactive and impulsive at home and school Symptoms evident in preschool had SEIT who did good behavioral treatment at home and school. No episodes. IQ and achievement testing normal. Steve said what makes him mad: when my mom tells me to do stuff I dont want to do; too much work in school [which is too hard]; I need help and the teacher said wait.

Short fuse, irritable and easily annoyed

Steves treatment history

Began ADHD medication in 1st grade takes Adderall XR 20 mg; in play therapy Depakote and Trileptal havent helped his mood or aggression Behavior modification started in preschool wasnt continued at school or at home Problems at home included lack of consistency between parents (divorced) and aunt (partial care taker) Mom depressed; dad had anger management problems

SEVERE MOOD DYSREGULATION (SMD)Leibenluft et al., 2003

Abnormal mood (anger or sadness) : most days severe enough to be noticeable by parents, teachers, or peers Markedly increased reactivity to negative emotional stimuli. at least three times/ week for the past 4 weeks. Hyperarousal (ADHD sx): Insomnia; Physical restlessness; Distractibility; racing thoughts or flight of ideas; pressured speech;intrusiveness Onset under age 12 Bottom Line: SMD encompasses severe ADHD+ODD

Temper Dysregulation Disorder with Dysphoria

SMD
Very severe outbursts with trivial triggers; >3 Xs/week Hyperarousal (ADHD/Anx sx) Persistently negative mood between outbursts Outbursts and/or negative mood in at least 2 settings At least 12 months; onset in childhood Not just in current mania, MDD, dysthymia or psychosis X X X X age 12 X X X age 10 X

TDDD
X

Relative rates of ADHD, SMD and BP in the population

6 5 4

3 2 1 0
An xi e Co nd OD D AD HD De p. BP rd e r SM D CB CL CB CL

ty

uc t

Di so

att

JB P

Costello et al. AGP 1996, N=1,015 youth; 9, 11, 13 years Brotman et al. Bio Psych 2006, N=1,420 youth; 9, 11, 13 years Hudziak et al., Bio Psych 2005 SMD= Severe Mood Dysregulation

Psychopathology in Offspring of Parents with Bipolar Illness-metaanalysis

Offspring diagnosis
Children of parents with BP 52% 26.5% 5.4% 8.5% 20.6% Children of parents without BP

Significance

Any mental disorder Affective disorders Bipolar disorder Unipolar depression Non-affective disorder

29% 8.3% 0% 7.5% 20.4%

n=973, P < .00001 n=614, P < .00001 n=795, P < .0005 n=350, n.s. n=505, n.s.

Lapalme et al., Canadian Journal of Psychiatry 42:623-31, 1997Lapalme,

GCarlson, MD Hodgins, & LaRoche (1997).

2 types of families

Parents with complex mood and behavior problems have offspring who carry similar diagnoses; that appears to be different from classic manic depression. Offspring of classic manic depressives (e.g.Amish; parents who are lithium responsive) still have a greater chance of developing bipolar disorder but their course is more benign.
1. Faraone SV, et al. Am J Med Genet. 1998;81(1):108-116. 2. Meyer S, et al. In press. 3. Duffy A, et al. Am J Psychiatry. 1998;155(3):431-433. 4. Grof P. J Clin Psychiatry. 2003;64(suppl 5):53-61.

How does treatment of kids with rages stack up

70 60 50 40 30 20 10 0 ADHD Anx/Dep SMD Bipolar LD % dx'ed % Rxed therapy

Bottom line: Many kids referred for treatment; many fewer get the right treatment

Do kids with rages/SMD develop manic depression as adults

Classic manic depression is not a significant outcome in long term follow up studies of children with hyperactivity/ADHD (Klein, 1999) Manic depression is not an outcome of children with severe aggression though these children do continue to have higher rates of aggression than other peopel; 3 y.o.s who are identified as impulsive, negativistic and distractible become unreliable, antagonistic and over-reactive adults (Caspi et al., 2003) Boys (age 8) with severe temper tantrums impulsive, moody, irritable, overly dramatic adults with poor job and marital histories (Caspi et al., 1990)
GCarlson, MD

Bottom line with Steve

Lots of things going on Although he was prescribed Adderall XR 20 mg, it wasnt working very well; needed much closer monitoring Lots of stress and inconsistency at home-needed behavioral program not play therapy Though he was smart enough, he needed more attention in school and a smaller class with a BIP If that isnt enough, it is worth adding an atypical antipsychotic He has ADHD and ODD; one could say he has severe mood dysregulation or TDDD; some might call him bipolar but it is unlikely he will develop adult manic depression; he is at high risk for drug abuse, drop out, and depression

How ADHD and BP are similar

They are both chronic disorders They are both highly heritable Both require medication and psychosocial treatment Both often have academic impairments Comorbidities may be similar (e.g. anxiety disorders, oppositional defiant disorder and substance abuse) Substance abuse is a complication of both

How are they different?

ADHD is not episodic (though it does fluctuate depending on childs interest or level of structure) and is developmental Key mood symptoms are absent (elation and grandiosity, though these can be misidentified easily if you really want the child to have bipolar disorder) Rates of BP in offspring are higher in families with BP; ADHD rates may be high in both if parents have comorbid BP + externalizing disorder Some outcomes may be similar (e.g. substance abuse) but long term studies of children with ADHD do not find rates of BP I, at least classically defined. Primary medication treatment is different

Why does it matter if there is a diagnostic mistake?

Parents feel they have a solution prematurely Clinicians dont look for other conditions that need to be identified; and the differential diagnosis is much broader than ADHD but that is the easiest to discuss Everyone assumes there will be a connection to bipolar disorder in adulthood Or that medications for bipolar disorder will clean things up nice.

Why does it matter if there is a diagnostic mistake

ADHD-do you use ADHD meds instead of? In addition to? Not at all? PDDspectrum - What kind of educational intervention will be necessary because of language and social issues? Psychosis NOS-Will this be stable quirkiness, schizophrenia prodrome, or mood disorder prodrome Organic brain syndrome - are there neurological tests that will be needed Traumatized child-is there past or current abuse that needs dealing with? For all conditions, how does the prognosis change?

When a parent describes mania in the child

The teacher sees moderate to severe executive function problems-66% ADHD -56% manic sx-36% PDD spectrum-26% ODD-25% What the child has: ADHD-56% ODD 35% PDD spectrum 33% severe anxiety 20% including PTSD bipolar disorder 18%

Status of Double Blind, Placebo Controlled trials and FDA approval of drugs for acute mania
Drug lithium divalproex Age <18 Approved in teens FDA required study (-); another study (+) olanzapine + Approved down to age 13 carbamazepine ER + Being studied risperidone + Approved to age 10 quetiapine + Approved to age 10 ziprasidone + positive aripiprazole + Approved to age 10 topiramate negative negative Not studied oxcarbazepine negative For dep lamotrigine Being studied
recurrence

Age >18 + +

Lamotrigine for Bipolar Students (LAMBS)

Lamotrigine is a medication approved for adults and is being tested in youth for stabilizing symptoms of bipolar mania and depression We are doing a free treatment trial. If you have a child between the ages of 10-17 who is being treated but isnt completely better and still has symptoms of mania (HIPERS) call Greg Carlson at 632-8828

Effect size of drugs in acute mania and aggression

Children and teens adults

mania
Lithium Divalproex .31 .28
Zip .48 to Ris .81

aggression

mania
.5 .23 to .62

Atypicals
Haloperidol

Ris .9
.8 but many AEs

Ari .36 to Ris .71

Thioridizine
Stimulants atomoxetine

.35
.78 .18

a agonists

.5

NNH
child sleepy Wt gain 7.0 akath eps 30.3 9.8 n/a sleepy adult Wt gain 84 akath eps 11.9 8.0 33.3 ns n/a

SGAs

4.6

7.1

Lithium n/a

n/a

90.1 ns 8.7 16.7

A-Cs

19.1 ns

n/a

n/a

Treatment implications
Mania/BP Lithium Depakote Antipsychotics antidepressants ADHD meds Specific I.E.P. Language rx psychotherapy FFT psychoed CBT ? X X X X X X X X MDD PDD abuse aggression X X X X X ADHD

X
X Soc skills CBT therapy X If comorbid Beh mod Beh mod

CPS

Treatment approach for most children with temper dysregulation

Good diagnostic assessment

It matters if ADHD or anxiety or PDD or learning disability or something else is underlying the rages

Maximize the treatment of the base condition

If symptoms remain, add another medication AAP, CAP or mood stabilizer

Keep careful records of frequency, intensity, number and duration of outbursts

TREATMENT IMPLICATIONS OF SEVERE MOOD DYSREGULATION/TDDD

Executive function Mood regulation Language Social

Medication management
ADHD treatment Anti-aggressive/anti Psychotic medications mood stabilizers Understand triggers Keep situation CALM

Psychological and Psychoeducational

Educate family members Figure out childs deficits Get evaluation-psych testing and language testing often useful if parent has a psychiatric disorder, get it treated!

Incidence of Acute Psychiatric Hospitalization Increased Markedly

Overall Change, 1996-2003 1996-1997 1998-1999 2000-2001 2002-2003 Discharges LOS Children
Discharges per 10,000 persons ... Length of Stay (Mean)............... 16.03 12.15 20.86 12.67 20.24 12.71 26.06 11.11

62.62%

-8.56%

Adolescents
Discharges per 10,000 persons ... Length of Stay (Mean)............... 58.97 8.18 67.65 7.52 85.97 7.25 83.33 7.14

41.31%

-12.66%

Adults
Discharges per 10,000 persons ... Length of Stay (Mean)............... 112.90 8.11 109.62 7.34 118.94 7.17 129.63 7.11

14.82%

-12.28%

HOSPITAL DISCHARGES 1996-2003

1996-7
Bipolar: Conduct Problems: Developmental: 4.26 per 10,000 4.50 per 10,000 0.49 per 10,000

2002-3
11.70 per 10,000 4.51 per 10,000 1.19 per 10,000

% Change
+174% +2% +146%

Children
25

Per 10,000 persons

20

15

10

BIPOLAR DX

1996-7 Conduct Bipolar

1998-9 Depression

2000-1 Psychosis Anxiety

2002-3 Developmental

DO CHILDREN WITH RAGES HAVE BIPOLAR DISORDER OR TEMPER DYSREGULATION

N = 29 Mean age; was 9.2 (2.1) years, 87% were male, 68% white. Mean LOS 36.8 +22 days. 72% special education 97% of parents described major explosive outbursts occurring several times a week 61% of parents said daily for at least a year. Outbursts lasted up to 30 minutes, and over an hour in 35% of cases. Outbursts consisted of threats, insults, throwing things, property destruction, and physical aggression.

TEMPER DYSREGULATION WITH DYSPHORIA ON A CHILDRENS INPATIENT UNIT

BE observation % of TDDD sample

Irritability

51.7%

n/a

Explosiveness
Temper Dysregulation Disorder (TDDD) % manic symptoms from CMRS-P (Score >20)

51.7%
31% 51.7%

n/a
n/a 55.6%

emotional lability

52.4%

100%

TEMPER DYSREGULATION WITH DYSPHORIA ON A CHILDRENS INPATIENT UNIT BE diagnosis N=29 % of TDDD sample

ODD
ADHD Comorbid ADHD and ODD:

61.9%
76.2%

88.9%
88.9%

Neither ADHD nor ODD

ADHD without ODD ODD without ADHD

6.9%
31.0% 6.9%

0
11.1% 11.1

Both ADHD and ODD

PDD Anxiety disorder Major depressive episode Manic episode

55.2%
20.7% 41.4% 13.8% 6.9%

77.8%
33.3% 22.2% 0 0

% language disorder

62.1%

77.8%

CONCLUSION SO FAR
If you attribute the rages that prompt admission to acute mania, you should see symptoms of mania during hospitalization Such symptoms were rarely seen However, of the 97% of children whose parents described what may be called temper dysregulation disorder with dysphoria

What is YOUR experience?

Only 1/3 continued to have those symptoms while hospitalized