mania & adhd

8/13/2019 Mania & ADHD

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Mania and ADHD What should you know?

Why should you care?

Gabrielle A. Carlson, MDProfessor of Psychiatry and Pediatrics

Director, Child and Adolescent PsychiatryStony 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 thatattention 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 personobserves it- present in different settings

• It is imPAIRING: interfering with child’s

functioning at home, with peers, with

family, and/oror with his/her selfesteem or

development.



“Hyperkinetic Child Syndrome”-Laufer and Denhoff, 1957

SYMPTOM DESCRIPTOR DSM IV

ADHD

Hyperactivity Involuntary and constant overactivity that greatly

surpasses normal

YES

Poor

Concentration

Frequent shifting from one activity to another YES

Variability Behavior is unpredictable. "Sometimes he is good,

sometimes bad"

NO

Irritability/

Explosiveness

Fits of anger easily provoked ; reactions almost

volcanic in intensity

NO

Impulsiveness Does things on the spur of the moment. Cannot delaygratification YES

Sleep

disturbance

Falls asleep at proper time but wakens after only a few

hours "rampaging through the house in hyperactive,

noisy, sleep-disturbing play"

NO

G. Carlson, 2009



OppositionalOppositional

Defiant DisorderDefiant Disorder

ADHD aloneADHD alone

TicTic

DisDis..

ConductConduct

DisorderDisorderAnxietyAnxiety

DisorderDisorder

MoodMood

DisDis..

31%

4%14%

40%

34%

11%

Co-Occurring Disorders in MTA Children

(n=579)



—Age—

Inattentio

n

Course of the Disorder

Though less than in childhood, it is stillgreater than In non-ADHD peers; verbal

> physical

Less than in childhood;

more often verbal and

cognitive than non-AADHDsame age peers



Outcome of ADHD

"Developmental Delay" - about 30% outgrow the disorder by youngadulthood (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 isn’t 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 Effect Size

Amphetamine 0.92

Methylphenidate 0.80

Atomoxetine 0.73

Guanfacine ER 0.73

Clonidine 0.58*

Modafinil 0.49

Bupropion 0.32

Diet without additives 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 Moderate Severe

When obvious Elementaryschool

preschool Age <3

Where it

manifests

Unstimulating

situations;homework time

School -class and

playground;Home-except computer

Everywhere

and anywhere

Untreatedoutcome

Worsens insecondaryschool

underachievement

Disorganization anddefiance; worse insecondary school

underachievement

aggression;peer problems;drugs,

underachievement

comorbidity Oftenuncomplicated

LD, ODD,anxiety,depression

LD, ODD/CD,other disorders



ADHD severity and treatment

Mild Moderate Severe

Educational

interventions

Structure

PRN tutoring

accommodations

Classification; ?

Regular class

SEDclassroom;sometimeshospitalization

Home

intervention

Structure;

behavior mod PRN

Behavior modification

needed

Behavior mod

Social andmental healthrx

medication If above strategiesfail and child slips

academically andbehaviorally

During school and forhomework; +/-

elsewhere dependingon impairment

Many medicationtrials; often

combinedmedications

Therapygoals

Psychoeducation

Organizational

skills; selfesteem help

Psychoeducation

Organizationalskills; self esteem

help

Aggression,anger control

Mood

stabilization



MTA: % ―Normalized‖ at 14 Months

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.

88%

68%

56%

34%

25%

0%

20%

40%

60%

80%

100%

Controls Comb MedMgt Beh CC



=

?

Manic depression or rages?



For office-based visits with a mental disorder, rates went

from .42% (n=25) in 1994 to 6.7% (n=1003)

Increase in BP

Diagnosis in youth

from nationallyrepresentative

outpatient office

visits(Moreno et al., 2007)

% of all



Remember these acronyms

• Mania: H*I*P*E*R*S

– Hyperactivity (goal directed), Irritability,Psychosis (grandios i ty ), E lated/expansive

mood, Rapid speech/Racing thoughts, Sleep

(doesn’t need it or want it)

• Depression: D*U*M*P*S – Definite personality change, Undeniable drop in

grades, Morbid/suidical, Pessimistic, Somatic

• Illness, drugs mania, called 2o

• Superimposed on other conditions

• Symptoms occur concurrently in episodeslasting 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 Complicationsin Children and Adults, 2009



GCarlson, MD

Case #1 Classic Bipolar I Disorder

• Nicola -14+ years old; shy, nice , no behavior problems or

substance abuse• Age 10, brief depressive episode after Grandma’s death; treated

with psychotherapy; increased anxiety related to school

demands in middle school.

• Several weeks before referral- parents said Nicola’s 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 using the vacuum cleaner at 6 am.



GCarlson, MD

Nicola continued

• Mental status: Nicola loud, intrusive, talked fast and

laughed loudly. Hard to follow her train of thought-she rapidly changed the subject to seeminglyunrelated topics.

• Convinced a TV actor whom she had been trying tocontact, would call her and she’d have a relationship

with him. She used her cell phone to try to call him.

• Became suspicious and hostile when asked aboutdrug use which she adamantly denied; She wouldnot allow the interviewer to see her parents alone,

likewise, didn’t want to be interviewed alone.

• She expressed a fear that her food may have beenpoisoned and that her brain had been damaged.



Steve

• 8 year old, 3rd grade boy in regular educationwith explosive outbursts (throws chairs,sweeps stuff off of desks, attacks staff) – Short fuse, irritable and easily annoyed

• Chronically hyperactive and impulsive athome and school

• Symptoms evident in preschool – had SEITwho did good behavioral treatment at homeand school. No episodes.

• IQ and achievement testing normal.• Steve said what makes him mad: “when my

mom tells me to do stuff I don’t want to do;too much work in school [which is too hard]; Ineed help and the teacher said “wait”.



Steve’s treatment history

• Began ADHD medication in 1st

grade• takes Adderall XR 20 mg; in play therapy

• Depakote and Trileptal haven’t helped his mood

or aggression

• Behavior modification started in preschool wasn’t

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 managementproblems



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

• Abnormal mood (anger or sadness) : most dayssevere enough to be noticeable by parents,teachers, or peers

• Markedly increased reactivity to negative

emotional stimuli. at least three times/ week forthe past 4 weeks.

• Hyperarousal (ADHD sx): Insomnia; Physicalrestlessness; 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 TDDDVery severe outbursts with

trivial triggers; >3 Xs/week

X X

―Hyperarousal‖ (ADHD/Anx sx) X

Persistently negative mood

between outbursts

X X

Outbursts and/or negative

mood in at least 2 settings

X X

At least 12 months; onset in

childhood

age 12 age 10

Not just in current mania, MDD,

dysthymia or psychosis

X X

R l ti t f ADHD SMD d BP i th



Relative rates of ADHD, SMD and BP in thepopulation

0

1

2

3

4

5

6

A n x i e t y

C o n d u c t

O D D A D H D

D e p . D i s o r d e r

B P S M D C B C L a t t

C B C L J B P

%

Costello et al. AGP 1996, N=1,015 youth; 9, 11, 13 yearsSMD= Severe Mood

DysregulationBrotman et al. Bio Psych 2006, N=1,420 youth; 9, 11, 13 years

Hudziak et al., Bio Psych 2005



GCarlson, MD

n=614,

P < .00001

8.3%26.5%Affective disorders

n=505, n.s.20.4%20.6%Non-affective disorder

n=350, n.s.7.5%8.5%Unipolar depression

n=795,

P < .0005

0%5.4%Bipolar disorder

n=973,

P < .00001

29%52%Any mental disorder

Children of

parents without

BP

Children of

parents with

BP

Offspring diagnosis

Psychopathology in Offspring of Parents withBipolar Illness-metaanalysis

Lapalme et al., Canadian Journal of Psychiatry 42:623-31, 1997Lapalme, Hodgins, & LaRoche (1997).

Significance



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 courseis 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

0

10

20

30

40

50

60

70

ADHD Anx/Dep SMD Bipolar LD

% dx'ed% Rxed

therapy

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

right treatment



GCarlson, MD

Do kids with rages/SMD develop manicdepression as adults

• Classic manic depression is not a significant

outcome in long term follow up studies of childrenwith ―hyperactivity‖/ADHD (Klein, 1999)

• Manic depression is not an outcome of children withsevere aggression – though these children docontinue to have higher rates of aggression thanother peopel;

• 3 y.o.s who are identified as impulsive, negativisticand distractible become unreliable, antagonistic and

over-reactive adults (Caspi et al., 2003)

• Boys (age 8) with severe temper tantrumsimpulsive, moody, irritable, overly dramatic adults

with poor job and marital histories (Caspi et al., 1990)



Bottom line with Steve

• Lots of things going on• Although he was prescribed Adderall XR 20 mg, it

wasn’t working very well; needed much closermonitoring

• Lots of stress and inconsistency at home-neededbehavioral program not play therapy

• Though he was smart enough, he needed moreattention in school and a smaller class with a BIP

• If that isn’t enough, it is worth adding an atypicalantipsychotic

• He has ADHD and ODD; one could say he has “severemood dysregulation” or TDDD; some might call him“bipolar” but it is unlikely he will develop adult manicdepression; 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 fluctuatedepending on child’s interest or level of structure) andis developmental

• Key mood symptoms are absent (elation andgrandiosity, 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 havecomorbid BP + externalizing disorder

• Some outcomes may be similar (e.g. substance abuse)but long term studies of children with ADHD do not findrates 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 don’t look for other conditions thatneed to be identified; and the differential

diagnosis is much broader than ADHD butthat is the easiest to discuss

• Everyone assumes there will be a connectionto bipolar disorder in adulthood

• Or that medications for bipolar disorder willclean things up nice.



Why does it matter if there is a diagnostic

mistake

• ADHD-do you use ADHD meds instead of? In additionto? Not at all?

• PDDspectrum - What kind of educational interventionwill 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 trialsand FDA approval of drugs for acute mania

Drug Age >18 Age <18lithium + Approved in teens

divalproex + FDA required study (-);another study (+)

olanzapine + Approved down to age 13

carbamazepine ER + Being studiedrisperidone + Approved to age 10

quetiapine + Approved to age 10

ziprasidone + positive

aripiprazole + Approved to age 10topiramate negative negative

oxcarbazepine Not studied negative

lamotrigine For deprecurrence

Being studied



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 achild between the ages of 10-17 who is being

treated but isn’t completely better and still has

symptoms of mania (HIPERS)

• call Greg Carlson at 632-8828



Effect size of drugs in acute mania andaggression

Children and teens adults

mania aggression mania

Lithium .31 .5

Divalproex .28 .23 to .62 Atypicals Zip .48 to

Ris .81Ris .9 Ari .36 to

Ris .71

Haloperidol .8 but many AEs

Thioridizine .35Stimulants .78

atomoxetine .18

a

agonists .5



NNH

child adult

sleepy Wt

gain

akath

eps

sleepy Wt

gain

akath

eps

SGAs 4.6 7.0 30.39.8

7.1 84 11.98.0

Lithium n/a n/a n/a 90.1

ns

33.3

ns

A-Cs 19.1 ns n/a n/a 8.7 16.7 n/a



Treatment implications

Mania/BP MDD PDD abuse aggression ADHD

Lithium X X

Depakote X X X

Antipsychotics X X X

antidepressants X X X

ADHD meds X X X

Specific I.E.P. ? X

Language rx X If comorbid

psychotherapy FFTpsychoed

CBT Soc

skills

CBTtherapy

Beh mod Beh

mod

CPS X



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 SEVEREMOOD DYSREGULATION/TDDD

Executive function Mood regulation Language Social

Medication management

ADHD treatment

Anti-aggressive/anti

Psychotic medications“mood stabilizers”

Understand “triggers”

Keep situation CALM

• Educate family members

• Figure out child’s deficits

•

Get evaluation-psych testingand language testing often useful

• if parent has a psychiatric

disorder, get it treated!

Psychological and

Psychoeducational



Incidence of Acute PsychiatricHospitalization 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...


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 ...


112.90

8.11

109.62

7.34

118.94

7.17

129.63

7.11

14.82% -12.28%



Children

0

5

10

15

20

25

1996-7 1998-9 2000-1 2002-3

P

e r 1 0 , 0

0 0

p e r s o n s

Conduct Bipolar Depression Psychosis Anxiety Developmental

1996-7 2002-3 % Change

Bipolar: 4.26 per 10,000 11.70 per 10,000 +174%

Conduct Problems: 4.50 per 10,000 4.51 per 10,000 +2%

Developmental: 0.49 per 10,000 1.19 per 10,000 +146%

HOSPITAL DISCHARGES 1996-2003

BIPOLAR

DX



• 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 physicalaggression.

DO CHILDREN WITH RAGESHAVE BIPOLAR DISORDER

OR ―TEMPER DYSREGULATION‖



BE observation % of TDDD

sample

Irritability 51.7% n/a

Explosiveness 51.7% n/a

Temper Dysregulation

Disorder (TDDD)

31% n/a

% manic symptoms from

CMRS-P (Score >20)

51.7% 55.6%

emotional lability 52.4% 100%

TEMPER DYSREGULATION WITH

DYSPHORIA ON A CHILDREN’S

INPATIENT UNIT

TEMPER DYSREGULATION WITH DYSPHORIA



BE diagnosis

N=29

% of TDDD

sample ODD 61.9% 88.9%

ADHD 76.2% 88.9%

Comorbid ADHD and ODD:

Neither ADHD nor ODD 6.9% 0 ADHD without ODD 31.0% 11.1%

ODD without ADHD 6.9% 11.1

Both ADHD and ODD 55.2% 77.8%

PDD 20.7% 33.3% Anxiety disorder 41.4% 22.2%

Major depressive episode 13.8% 0

Manic episode 6.9% 0

% language disorder 62.1% 77.8%

TEMPER DYSREGULATION WITH DYSPHORIA

ON A CHILDREN’S INPATIENT UNIT



CONCLUSION SO FAR

• If you attribute the rages that promptadmission to acute mania, you should seesymptoms of mania during hospitalization

• Such symptoms were rarely seen

• However, of the 97% of children whoseparents described what may be called“temper dysregulation disorder withdysphoria” – Only 1/3 continued to have those

symptoms while hospitalized• What is YOUR experience?

mania & adhd

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