Copyright © The REACH Institute. All rights reserved. Pediatric Bipolar Disorder

Copyright © The REACH Institute. All rights reserved.

Pediatric Bipolar Disorder

http://www.thereachinstitute.org/


Learning ObjectivesLearning Objectives

In order to effectively use medications for pediatric behavioral health problems, participants will learn to:

1) Identify and differentiate among pediatric behavioral health problems, especially bipolar disorder, depression, ADHD and oppositional defiant disorder

2) Describe treatment algorithms and evidence-based medications used to treat bipolar disorder


AgendaAgenda

• We will review different presentations and diagnostic dilemmas associated with pediatric bipolar disorder

• We will discuss a treatment algorithm for pediatric bipolar disorder


Despite the complexity of diagnosis and management, pediatricianshave an important collaborative role in referring and partnering inthe management of adolescents with bipolar disorder.

This report presents the classification of bipolar disorder as well as interviewing and diagnostic guidelines. Treatment options are described, particularly focusing on medication management and rationale for the common practice of multiple, simultaneous medications. Medicationadverse effects may be problematic and better managed with collaboration between mental health professionals and pediatricians.

Case examples illustrate a number of common diagnostic and management issues.

Pediatrics 2012;130:e1725–e1742

RESOURCE SLIDE:Collaborative Role of the Pediatrician in the Diagnosis and Management of Bipolar Disorder in Adolescents.

Shain BN, et al.


The Assessment ofBipolar Disorder in

Children and Adolescents

The Assessment ofBipolar Disorder in

Children and Adolescents


What is Johnny’s Diagnosis?(see workbook page I 1.1)

Pick one best answer:

What is Johnny’s Diagnosis?(see workbook page I 1.1)

Pick one best answer:

A. ADHD

B. Bipolar Disorder

C. Oppositional Defiant Disorder

D. ADHD and Oppositional Defiant Disorder

E. Generalized Anxiety Disorder

F. Major Depressive Disorder

G. All of the above


Lifetime Prevalence of Bipolar Disorder in the USA

• Adults (NCS Replication Study, Merikangas et al. 2007)

– Bipolar I Disorder: 1.0%

– Bipolar II Disorder: 1.1%

– Bipolar Subthreshold: 2.4%

• Adolescents– Bipolar Disorder: 1.0-1.4% (e.g., see Shaffer D et al. 1996

[MECA]; Kessler RC et al., 2011)

• Children– ???


DSM-5 Manic Episode• A DISTINCT PERIOD of abnormally and persistently

elevated, expansive, or irritable mood; accompanied by increased energy/activity, lasting at least 1 week or resulting in hospitalization– (or any duration if hospitalization because of mania is necessary)

• At Least Three:– Inflated self esteem or grandiosity

– Decreased need for sleep

– More talkative than usual

– Flight of ideas or racing thoughts

– Distractibility

– Increase in goal-directed activity or psychomotor agitation

– Excessive involvement in pleasurable activities potential for painful consequences

• Causes a marked impairment in occupational or social functioning


Developmental IssuesDevelopmental Issues

• Similarities between adults and children with Bipolar Disorder– elated mood, grandiosity, hypersexuality, decreased

need for sleep, flight of ideas, racing thoughts, social intrusiveness (Geller et al. J Child and Adolescent Psychopharmacology 10:157-164, 2000)

• Importance of developmental differences in presentation


• BP-NOS

• Irritability

• Mood Lability

• Hallucinations

• Worse course

• ADHD

• ODD

• BP-I-II

• More Severe Depressions

• Melancholic

• Atypical

• Suicidality

• More typical and severe mania

• Elation

• Grandiosity

• Substance abuse

Children Adolescents

Developmental Differences Between Bipolar Children and Adolescents


Developmental Differences in the Expression of Manic and Depressive Symptoms


Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56.


SYMPTOM ADULT CHILD

Racing thoughts

Jumping from one thought to another in an illogical manner

Describes mind is like a video on fast forward

Pressured speech

Hard to interrupt and not phased when you do

Child talks continuously and difficult to redirect


Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56.


The Broad PhenotypeThe Broad Phenotype• There may be a large group of children who show

manic symptoms– Especially the affective storms & rages

– Don’t clearly cycle between mood states

– May not have bipolar in family pedigree

– Severe Mood Dysregulation (Leibenluft et al 2003)

• Are these bipolar cases? – Will they grow up to look more classic?

– Safety screen of neglect/abuse

– Possible medical conditions like temporary lobe epilepsy, hyperthyroidism, alcohol-related neurodevelopment, Wilson’s Disease


Need For Better Diagnostic Criteria For Pediatric Bipolar Disorder

Need For Better Diagnostic Criteria For Pediatric Bipolar Disorder

• DSM-4 & 5: no model is perfect, but even imperfect models can help

• DSM criteria based primarily on adult research

• Changes with the Adult Diagnostic “Spectrum” of Bipolar disorder

– “Classic” Type I Bipolar Disorder (less than 50% of adults)

– Type II Bipolar Disorder, also mixed, rapid cycling

• DSM 5 Disruptive Mood Dysregulation Disorder


Disruptive Mood Dysregulation Disorder, DSM-5

A. Severe recurrent temper outbursts

Verbal and/or behavioral, grossly out of proportion in intensity or duration,

inconsistent with developmental level

B. Frequency >=3/week

C. Mood between temper outbursts:

Persistently negative (irritable, angry, and/or sad)

Negative mood is observable by others

D. Duration; Criteria A-C >= 12 months

E. >= 2 settings

F. Chronological age >= 6 years (or equivalent developmental level).

G. .Onset before 10 years.

H. No history of (elevated) manic mood with associated B criteria for >= 1day

I. Not occur exclusively during the course of a Psychotic or Mood Disorder; not

better accounted for by another mental disorder (e.g., PDD, PTSD).

Can co-occur with ODD, ADHD, CD


Bipolar Symptoms Shared with Other Childhood Disorders

Bipolar Symptoms Shared with Other Childhood Disorders

Mania MDD ADHD ODD Anxiety

Elated mood

67% Low frustrationtolerance

Touchy/Easilyannoyed

Irritability

Hyperactivityagitation

Agitation Hyperactivity Restlessnessagitation

Distractibility Poorconc.

Distractibility Difficulty inconcentration

Flight of ideas Communicationdisorders

Grandiosity

Impulsivity

Reduced sleep Insomnia Trouble settlingwakes early Initial insomnia

Poor judgment

Irritability


ADHD vs. BipolarADHD vs. Bipolar

• Irritability is non-specific: – Irritability does not = Bipolar

– Geller et al 2002 found irritability in 72% of Children with ADHD and 97.9% of Children with Bipolar Disorder

• Elation, grandiosity, flight of ideas/racing thoughts, decreased need for sleep and hypersexuality provide the best discrimination between ADHD and BD in children and adolescents (Geller et al 2002)


The Unipolar Depression vs.Bipolar Distinction

The Unipolar Depression vs.Bipolar Distinction

• First mood episode of Juvenile Bipolar Disorder is often a depressive episode

• MDD in children often associated with high rates of irritability…i.e., children with depression can present with irritable mood, not depressed mood

• Children and Adolescents with major depressive disorder can have very labile mood

• What do you mean by “mood swings?” – euthymia to depressed vs. depressed to manic or

hypomanic


Substance Abuse vs.Pediatric Bipolar Disorder

Substance Abuse vs.Pediatric Bipolar Disorder

• The substance abuse may mimic a bipolar presentation– Check urine drug screens, educate patients and

families

• There are high rates of co-morbid substance abuse in adolescents with bipolar disorder– The substance abuse must be addressed


Conduct Disorder vs.Pediatric Bipolar Disorder

Conduct Disorder vs.Pediatric Bipolar Disorder

• Conduct Disorder– The negative

behaviors areoften calculating and predatory

• Pediatric Bipolar– The negative

behaviors are secondary to grandiosity and risky, poor judgment


Bipolar or Psychosis?


Bipolar or Trauma?


With Pediatric Bipolar DisorderThere Are High Rates of

Co-occurring Psychiatric Conditions

With Pediatric Bipolar DisorderThere Are High Rates of

Co-occurring Psychiatric Conditions

• ADHD• ODD• Conduct Disorder• Learning Disabilities• Substance Abuse• Anxiety Disorders

Individually orin combination


A Family History ofBipolar Disorder

A Family History ofBipolar Disorder

• Take a careful family psychiatric history– Bipolar disorder in one parent = 5x odds of bipolar

disorder in child (but still only ~5% prevalence; LaPalme et al., 1997), still less than likelihood of ADHD

– Bipolar disorder in parents, grandparents, and siblings is clinically meaningful but doesn’t rule out “bad” ADHD

– The presence of bipolar disorder in more distant relatives may not confer greater genetic risk

– No clear family history doesn’t rule out pediatric bipolar disorder


Pediatric Bipolar Rating ScalesPediatric Bipolar Rating Scales

• Young Mania Rating Scale for Parents P-YMRS (Gracious et al. JAACAP,2002) – the scale can be found at www.healthyplace.com/bipolar/p-ymrs.asp

• General Behavioral Inventory, GBI (Findling et al. Bipolar Disorder, 2002)– Self and parent report ages 5-17– Very long tool 73 mood items

• Life Mood Charts– Asking about mood symptoms throughout the patient’s life– Can be found at www.dballiance.org

• These rating scales do a better job of ruling out pediatric bipolar disorder then ruling it in

• Still very helpful to follow symptoms to assist with diagnosis and to follow symptoms

http://www.healthyplace.com/bipolar/p-ymrs.asp


SummarySummary• In evaluating pediatric bipolar disorder look for classic

criteria, i.e., a DISTINCT EPISODE, different from the child’s normal state, characterized by:

– elevated mood, grandiosity, decreased need for sleep, racing thoughts

• High rates of psychiatric co-morbidity– Especially ADHD, ODD, Conduct Disorder and Learning

disabilities

• Careful family history– Focus on first and second degree relatives

• Rating scales do a better job of ruling out pediatric bipolar disorder then ruling it in

• If significantly concerned get a child psychiatry consultation


Bipolar DisorderTreatment Options

Bipolar DisorderTreatment Options


• If neglect/abuse, crisis intervention

• Mental Health Specialist for diagnostic assessment and sometimes concurrent treatment: CBT, social skills, problem solving, psych education.

• If bipolar, psychiatric assessment and treatment with on-going therapy, lab testing and medication treatment.

• Lab testing

• Medications review/ monitoring for side effects

• Inquire about concerns/safety

Bipolar Management


FDA Pediatric Labeling for BDFDA Pediatric Labeling for BD

Brand name Generic Name Indicated Age

Cibalith-S Lithium citrate12 and older

Eskalith Lithium CO3

12 and older

Lithobid Lithium CO3 12 and older

Risperdal Risperidone 10 and older

Abilify Aripiprazole 10 and older

Zyprexa Olanzapine 10 and older

Seroquel Quetiapine 10 and older


Atypical Antipsychotic Use for Pediatric Mania

Atypical Antipsychotic Use for Pediatric Mania

• Refer for hospitalization• Risperidone, target dose 2-4 mg/day, divided

doses• Start 0.5 mg qhs, add 0.5-1mg q. 3-4 days if well-

tolerated• Onset of action: 7 days; full efficacy in 4-6 weeks• Side effects: weight gain, sedation, elevated

prolactin• At baseline: fasting glucose, lipids, BMI, girth,

dietary consultation• Taper at 6 months


Treatment Algorithm for Mania/ Hypomania in Children and Adolescents

Stage 1 Monotherapy

Stage 2 Augmentation

Stage 3 2 drug combinations

Evaluate

Continue

1A: Mixed/ManicQuetiapine/ Aripiprazole/Risperidone

1B: Lithium/Valproate/Olanzapine/Ziprasidone

2: Add mood stabilizer to atypical or vice versa

3: 2 mood stabilizers + 1 atypical or 2 atypicals + mood stabilizer

Continue

Partial response or nonresponse

Positive response

Partial response

Evaluate

Negativeresponse

Positive response

Kowatch RA et al. Clinical Manual for the Management of Bipolar Disorder in Children and Adolescents. Arlington, VA: American Psychiatric Publishing, Inc; 2008.


Lithium UseLithium Use

• Target dose of 30 mg/kg/day– Start outpatients 25 mg/kg/day– Serum level of 0.9 -1.1 mEq/L

• Onset of action: 7-14 days– Full efficacy in 6-8 Weeks

• Side effects– Weight gain/Exacerbation of Acne/Enuresis/Hypothyroidism

• Baseline labs: – CBC/diif, pregnancy, EKG, renal & thyroid function, calcium

• Q 6 Months– Lithium Level, TSH, BUN, serum creatinine


Management of Common Lithium Side EffectsManagement of Common Lithium Side Effects


Divalproex Sodium Use in ChildrenDivalproex Sodium Use in Children

• Target dose of 20 mg/kg/day– Start outpatients at 15 mg/kg/day– Serum level of 80-120 mg/mL

• Onset of action: 7-14 days– Full efficacy in 4-6 weeks

• Labs: pregnancy, CBC, platelets, LFTs

• Monitor for PCOS


Divalproex/Valproate Side EffectsDivalproex/Valproate Side Effects• Nausea, vomiting, diarrhea

• Tremor/Myoclonus

• Sedation, mental dulling

• Weight gain

• Hair loss, decreased platelets

• Liver toxicity, pancreatitis, hyperinsulinism, polycystic ovary syndrome (PCOS)

• FDA Warning Box– Hepatotoxicity: Hepatic failure resulting in fatalities has occurred in

patients receiving valproic acid and its derivatives. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants…

– Pancreatitis: Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate.


Depression Switching toBipolar Disorder

Depression Switching toBipolar Disorder

• Prepubertal depression BD– Limited outcome studies

– 24/72 (33%) MDD children BD-I at age 20, 11/72 (11%) BD-II or hypomania (Geller et al., 2001)

• Adolescent depression BD– Limited studies

– 58 MDD inpatients followed up in 24 months Overall: 5/58 (8.6%) BD; 0/40 without psychotic symptoms, 5/18 (28%) with psychotic

symptoms (Strober et al., 1992)

– Epidemiological sample; 275 teens with MDD, < 1% BD by age 24 (Lewinsohn et al., 2000)

– 5/26 (19%) of MDD adolescents had BD after ~7 year follow-up (compared to 0% of controls) (Rao et al.,1995)


Switching to Bipolar Disorder with Antidepressants:

Switching to Bipolar Disorder with Antidepressants:

• Antidepressants may induce mania in children with a bipolar diathesis

– In a survey of child and adolescent psychiatrists: 10/228 (4.4%) of children under 13 y/o treated by psychiatrists switched to BD (Reichart & Nolen, 2004)

– Treatment for Adolescent Depression Study (TADS), of 439 12-17 year olds: 0 switches to BD after 12-week follow-up (2004)

– large private insurance database, 5.4% switch rates, increased risk for youth on antidepressants and risk greatest for age group of 10-14 y/o (San Martin et al., 2004)


Switching to Bipolar Disorder with Stimulants:

Switching to Bipolar Disorder with Stimulants:

• Concerns that stimulants may precipitate mania or destabilize children with bipolar who are not stabilized on other medications

– In the Multimodal Treatment Study of Children with ADHD (MTA), children with ADHD and some manic symptoms responded well to stimulants with decrease in ADHD symptoms and without increased rates of developing bipolar disorder (Galanter et al 2003, 2005)

– “Follow-back” study of children originally diagnosed and treated for “minimal brain dysfunction.”

Those diagnosed with bipolar spectrum disorders as young adults had responded well to stimulants as children

Those children with more comorbidities did not develop higher rates of bipolar as compared to those with uncomplicated ADHD (Carlson et al 2000)

However…some medications (including stimulants) can increase mood instability and irritability


Expert Panel Question & AnswerExpert Panel Question & Answer

• Treat or Refer?

• ADHD versus BD?

• When to add medications vs. switch medications?

• Other questions?


REMINDER: Please fill out Unit I

evaluation


Getting it Paid For: Self-Study

Do you know how to code these cases so you will get paid?

Do you know when to use these coding variations?

Getting it Paid For: Self-Study

Do you know how to code these cases so you will get paid?

Do you know when to use these coding variations?


Johnny’s Visit: DiagnosisJohnny’s Visit: Diagnosis

At this visit, with information available to us, the following are all plausible as primary diagnosis:– 799.2 Signs and sxs. Involving emotional state– 799.21 Nervousness– 799.24 Irritability– 312.9 Disruptive behavior disorder, NOS– 313.81 Oppositional defiant disorder– 314.9 Unspecified hyperkinetic syndrome


Johnny’s Diagnosis: PrimaryJohnny’s Diagnosis: Primary Without more information, cannot

make formal dx. Of ADHD, bipolar disorder, generalized or specific anxiety disorder, major depressive disorder

All the above certainly are possible


Johnny’s Diagnosis: Secondary Johnny’s Diagnosis: Secondary V40.0 Problems w/ learning V40.3 Mental and behavioral

problems, other behavioral problems V61.29 Parent-child problems, other 780.50 Sleep disturbance, unspecified


Johnny: Secondary DiagnosisJohnny: Secondary Diagnosis 313.83 Academic underachievement

disorder 799.51 Attention or concentration

deficit, not associated with attention deficit disorder

300.20 Other isolated or simple phobia


Johnny’s Visit: E/MJohnny’s Visit: E/M

E/M only –no report of rating scales or developmental testing

Complex Medical Decision Making:– Medical Diagnosis: Extensive– Data: Extensive– Risk: High

History:– HPI: 4+– ROS: 10+– PFSH: 2


Johnny’s Visit: 99215Johnny’s Visit: 99215

I would certainly advise home care plan oversight as this child could require a lot of non-face-to-face care!

Standardized rating scales could be extremely useful in obtaining information from multiple informants in a format allowing valid comparison of observations


Mood Stabilizer ToolboxMood Stabilizer Toolbox

Mood Stabilizer

Start at Target Serum Level

Monitor Watch Out For

Lithium 25-30 mg/kg/da

y

0.8-1.2 Meq/L

Renal/Thyroid Function

Dehydration toxicity

Valproate 15-20 mg/kg/da

y

85-110 μg/mL

Liver/Pancreas/Plats.

PCOSHyperammonemia

Carbamazepine

15-20 mg/kg/da

y

7-10 μg/mL

WBC/Plats. CYP450 Interactions


Atypical ToolboxAtypical Toolbox

Atypical Antipsychoti

c

Start at

(mg/day)

Target Dose

(mg/day)Monitor Watch Out

For

Risperidone 0.25-0.50

1-3 Weight/Height/BMI

EPS/TD

Aripiprazole 2.5-5 5-20 Weight/Height/BMI

EPS

Quetiapine 50-100 300-600 Weight/Height/BMI

Ziprasidone 20-40 80-160 Weight/Height/BMI

ECG

Take with food,Assess cardiac risk factors

Olanzapine 5 5-20 Weight/Height/BMI

Choles/FAs


RESOURCE SLIDEFDA-Approved Bipolar Disorder

Treatments in Adults

RESOURCE SLIDEFDA-Approved Bipolar Disorder

Treatments in AdultsAgents Manic Mixed Maintenance Depression

ATYPICALS

Aripiprazole (Abilify) + + + –Olanzapine (Zyprexa) + + + –Quetiapine (SEROQUEL) + – – +Risperidone (Risperdal) + + – –Ziprasidone (Geodon) + + – –

OTHER

Carbamazepine ER (EquetroTM) + + – –Divalproex DR (Depakote) + – – –Divalproex ER (Depakote ER) + + – –Lamotrigine (Lamictal) – – + –Lithium (Lithobid, Eskalith) + – + –Olanzapine/fluoxetine (Symbyax) – – – +

Slide courtesy of Robert Kowatch M.D.


RESOURCE SLIDEDBPRCTs for Pediatric Bipolar and Related Disorders: Mood Stabilizers

RESOURCE SLIDEDBPRCTs for Pediatric Bipolar and Related Disorders: Mood Stabilizers

Authors Treatment Sample Diagnosis Results

Geller et al. (1998)

Lithium N=25; 16.3 ± 1.2 y/o (12-18); Outpatient

Bipolar I or II, substance dependency

Li > PC (measures of psychopathology and urine tests)

Kafantaris et al. (2001)

Lithium (Discontinuation)

N=40; 15.2 ± 1.7 y.o. (12-18); Inpatient

BD-I manic episode, responders to Li

Li = PC in preventing exacerbation (although trend in favor of Li 52.6% vs. 61.9%)

Findling et al. (2005)

Lithium vs. Divalproex (Maintenance; stable after Li/DVP combo)

N=60; 10.8 ± 3.5 y.o. (5-17); Outpatient

BD-I or II Li = DVP (time to relapse, time to discontinuation)

DelBello et al. (2006)

Divalproex vs. Quetiapine

N=50; 15 ± 1.5 y.o. (12-18); Inpatient

Bipolar-I, manic or mixed episode

Quet = DVP (diff in YMRS scores); Quet > DVP (time to improvement and response/remission)

Donovan et al. (2000)

Divalproex (Crossover)

N=20; 13.8 ± 2.4 y.o. (10-18); Outpatient

*CD or ODD with explosive temper & mood lability

Phase 1: DVP > PC Phase 2: DVP > PC

Dineen-Wagner et al., (2006)

Oxcarbazepine N=116; 7-18 y.o.; Outpatient


Oxcarbazepine = PC (change in YMRS)


Topiramate N=56; 6-17 y.o.; Inpatient/outpatient


Discontinued early when adult studies failed to show efficacy; trend toward improvement

UNPUBLISHED DATA

Abbott; Unpublished data

Divalproex ER N=150; 10-17 y.o. BD Divalproex ER = Placebo; 4 week study only; >50% dec YMRS; DVP = 24%; Placebo = 28% ns;

Study/Sponsor

Ref N Sites AgeRange

Yr.

DXDesign

Duration(Days)

Dose(mg/day)

Response Rate

(YMRS)

Mean Weight Gain(kg)

Olanz./Lilly

TohenAm J

Psych.

161 26 10-17 BPD IManic,Mixed

DBPCRT2:1

21 10.4+4.5

49% 3.66+2.18

Risper./Janssan

AACAP2007

169 M 10-17 BPD IManic,Mixed

DBPCRT1:1:1

21 0.5-2.53-6

59%63%

1.91.4

Aripip/BMS

ACNP2007


DBPCRT1:1:1

28 1030

45%64%

0.90.54

Que/Astra-

Zeneca

ACNP2007

284 M 10-17 BPD IManic

DBPCRT1:1:1

21 400600

64%58%

1.7

Zipras/Pfizer

APA2008


DBPCRT2:1

28 80-160 -13.83 (Zipras)

-8.61(PBO)

-

RESOURCE SLIDEIndustry DB Placebo RCTs for Pediatric Bipolar

and Related Disorders: Atypicals

RESOURCE SLIDEIndustry DB Placebo RCTs for Pediatric Bipolar

and Related Disorders: Atypicals

Copyright ©2014The REACH Institute. All rights reserved.


RESOURCE SLIDEOther DB Placebo RCTs for Pediatric Bipolar and

Related Disorders: Atypicals

RESOURCE SLIDEOther DB Placebo RCTs for Pediatric Bipolar and

Related Disorders: Atypicals



Quetiapine as adjunct to Divalproex

N=30; 12-18 y.o. Bipolar-I, manic or mixed episode

Significant decreases in YMRS scores after 6 wks.

UNPUBLISHED DATA

Luis Rohde,Unpublished Data

Aripiprazole N=43; 8-17 y.o. BD-I or II and comorbid ADHD?

Aripiprazole > Placebo for YMRSDid not improve ADHD symptoms


RESOURCE SLIDE. Treatment Options for Pediatric Bipolar Disorder: Selected Open Trials

RESOURCE SLIDE. Treatment Options for Pediatric Bipolar Disorder: Selected Open Trials


MOOD STABILIZERS

Kafantaris et al. (2003)

Lithium N=100; 15.2 ± 1.9 y.o. (12-18); Inpatient

BD-I manic or mixed episode

≥33% improvement on YMRS: 63%; 26% remission

Patel et al. (2006) Lithium N=27; 15.6 y.o. (12-18); Inpatient

Bipolar; during depressive episode

↓ CDRS-R; 48% response; 30% remission

Kowatch et al. (2000)

Lithium vs. Divalproex vs. Carbamazepine

N=42; 11.4 y.o. (6-18); Outpatient

Bipolar-I or II All three efficacious; DVP > Li = CBZ (response rates and effect size)

Pavuluri et al. (2006)

Lithium (+ risperidone for non-responders)

N=38; 11.4 ± 3.8 y.o. (4-17); Outpatient

Preschool-onset bipolar ≥50% decrease on YMRS: 17/38 on Li alone; 18/21 with risperidone

Findling et al. (2006)

Lithium/Divalproex (after success w/ Li/DVP and relapse w/ monotherapy)

N=38; 10.5 y.o. (5-17); Outpatient

Bipolar-I or II 34 (89.5%) responded

Dineen-Wagner et al. (2002)

Divalproex N=40; 12.1 ± 3.6 y.o. (7-19); In-/Outpatient

Bipolar-I or II, manic, mixed, or hypomanic

22 (61%) improved on YMRS

Chang et al. (2006)

Lamotrigine (alone or added to current medications)

N=20; 15.8 ± 1.7 y.o. (12-17); Outpatient

Bipolar- I, II, NOS; during depressive episode

16 (84%) improved on CGI; 12 (63%) ↓ CDRS-R; 11 (58%) remitted

ATYPICALS

Biederman et al. (2005)

Risperidone N=30; 10.1 ± 2.5 y.o. (6-17)

Bipolar- I, II or NOS 70% response (based on CGI); ↓ YMRS scores

Frazier et al. (2001)

Olanzapine N=23; 10.3 ± 2.9 y.o. (5-14); Outpatient

BD-I manic, mixed, or hypomanic

Response rate: 14/23 (61%)


RESOURCE SLIDEHigher Level of Suspicion

• Family history of mood disorders

• Red Flag symptoms that occur together

• Early age of onset for depression

• Mood disorder with psychotic features

• Recurrent depressive episodes resistive to treatment

• Episodic presentation of ADHD


RESOURCE SLIDEDSM-5 Hypomanic Episode

• A distinct period of sustained elevated, expansive, or irritable mood for 4 days

• At least three:– Inflated self esteem or grandiosity– Decreased need for sleep– More talkative than usual– Flight of ideas or racing thoughts– Distractibility– Increase in goal-directed activity or psychomotor agitation– Excessive involvement in pleasurable activities with potential

for painful consequences• Unequivocal change in functioning observable by others• Does not cause a marked impairment in occupational or social

functioning or necessitate hospitalization


RESOURCE SLIDEMania vs. Hypomania

Criteria Manic Episode Hypomanic Episode

Mood Symptoms

“DISTINCT PERIOD OF Abnormally & persistently elevated, expansive, or

irritable mood.”

Same

Duration 7 days At least 4 days

Number of Symptoms

3 or more (4 if only irritable)

Same

Impairment Marked

Does not cause marked impairment; unequivocal

change in functioning; observable by others


Time ----> Time ---->

RESOURCE SLIDEVariations in BP Illness Courses

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RESOURCE SLIDEDistribution of Reported BD Age of Onset (yr.)

Goodwin & Jamison 2007


RESOURCE SLIDE: Mood Swings Quick Guide


RESOURCE SLIDE: Rates of Disorder: Children of Bipolar Parents vs. Control Parents

0

10

20

30

40

50

60

52

21

11 11

2624

4

29

40.8

3.6

11

17

3

Bipolar Offspring

Control Offspring

%

Birmaher et al Arch Gen Psychiatry 2009:66


RESOURCE SLIDE: Red Flag SymptomsSymptom Not Bipolar Possibly BP Disorder or

BP Spectrum

Rages/AggressionWhen told “no”, short, 5-10 min.

4-5 Xs/day, hours at a time, little provocation, “Egg Shell” sign

Decreased Need for Sleep

Initial/middle insomnia because of anxiety

3-4 day periods of “I only slept 4 hours and am feeling fine.”

Spontaneous Mood Shifts

Moody/angry around sibs and parents

Silly/giddly for hours in the AM; depressed and suicidal in the PM

High Risk Behaviors Project X Risky Business

Grandiosity“I can get into college somewhere with my 2.0 GPA”

“I don’t need to go to college to start the next Facebook”

Agitation with Antidepressant/SSRIs

Not if it resolvesPossibly, if manic SXs continue after SSRI is stopped.


RESOURCE SLIDE:The Diagnosis of Bipolar Disorder

in Children & Adolescents…

A Clinical Diagnosis Screening Instruments

CBCL or Parent GBI Helpful, but not Diagnostic Sensitive but not Specific

Interview of the Parent & Child/Adolescent Requires the clear history of an EPISODE,

different from the child’s normal self Family History Medical History Past Responses to Psychotropics?


RESOURCE SLIDE:

• PubMed from 1989 through 2010 for open-label and randomized controlled

• Trials published in English on the pharmacotherapy of pediatric mania.

• 46 open-label and randomized clinical trials of antimanic agents in pediatric bipolar disorder encompassing 2,666 subjects

Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review & Meta-analysis. Liu HY, Potter MP, Woodword Y, et. al.


RESOURCE SLIDE: Liu et al., 2011 Pharmacotherapy of Juvenile Bipolar Disorder:

# of Studies, # of Subjects, & Treatment Type

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RESOURCE SLIDE:Mood Stabilizers


RESOURCE SLIDE:Mood Stabilizers vs. Antipsychotics


RESOURCE SLIDE:Mood Stabilizers

Traditional Lithium Valproate

(Sodium Divalproex)

Carbamazepine

New/Novel * Gabapentin Lamotrigine Topiramate Tiagabine Oxcarbazepine Levetiracetam Zonisamide

* Not recommended for PCPs’ initiation

Documents

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