Download Assessment and Treatment of the Tough Cases: JBD and Psychosis

Pediatric Bipolar Disorder
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Learning 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
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Agenda
• We will review different presentations
and diagnostic dilemmas associated
with pediatric bipolar disorder
• We will discuss a treatment algorithm
for pediatric bipolar disorder
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RESOURCE SLIDE:
Collaborative Role of the Pediatrician in the Diagnosis
and Management of Bipolar Disorder in Adolescents.
Shain BN, et al.
Pediatrics 2012;130:e1725–e1742
Despite the complexity of diagnosis and management, pediatricians
have an important collaborative role in referring and partnering in
the 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. Medication
adverse 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.
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The Assessment of
Bipolar Disorder in
Children and Adolescents
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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
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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
– ???
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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
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Developmental 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
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Developmental Differences Between
Bipolar Children and Adolescents
Children
•
BP-NOS
Adolescents
•
BP-I-II
•
More Severe
Depressions
• Irritability
•
Melancholic
• Mood Lability
•
Atypical
•
Suicidality
• Hallucinations
• Worse course
• ADHD
• ODD
•
More typical and
severe mania
•
Elation
•
Grandiosity
•
Substance abuse
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Developmental Differences in the Expression
of Manic and Depressive Symptoms
SYMPTOM
ADULT
CHILD
Grandiosity
I’m the world’s greatest
lover,
The president will be
calling me for advice
I’m smarter than
my teacher; I am the
best writer in my whole
school
Decreased need
for sleep
Several nights in a row
without needing any
sleep and no sense of
fatigue
Needing only a few
hours of sleep and
engaging in activity in
the middle of the night
Hypersexuality
Unprotected sex with
multiple partners
Child propositions adult,
self stimulates in public
Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56.
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Developmental Differences in the Expression
of Manic and Depressive Symptoms
SYMPTOM
ADULT
CHILD
Racing
thoughts
Jumping from one
Describes mind is
thought to another in like a video on fast
an illogical manner
forward
Pressured
speech
Hard to interrupt and Child talks
not phased when you continuously and
do
difficult to redirect
Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56.
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The 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
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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
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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
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Bipolar Symptoms Shared with
Other Childhood Disorders
Mania
MDD
ADHD
ODD
Anxiety
Elated mood
Irritability
67%
Low frustration
tolerance
Touchy/
Easily
annoyed
Irritability
Hyperactivity
agitation
Agitation
Hyperactivity
Restlessness
agitation
Distractibility
Poor
conc.
Distractibility
Difficulty in
concentration
Communication
disorders
Flight of ideas
Grandiosity
Impulsivity
Poor judgment
Reduced sleep
Insomnia
Trouble settling
wakes early
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Initial insomnia
ADHD 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)
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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
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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
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Conduct Disorder vs.
Pediatric Bipolar Disorder
• Conduct Disorder
– The negative
behaviors are
often calculating
and predatory
• Pediatric Bipolar
– The negative
behaviors are
secondary to
grandiosity and
risky, poor
judgment
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Bipolar or Psychosis?
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Bipolar or Trauma?
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With Pediatric Bipolar Disorder
There Are High Rates of
Co-occurring Psychiatric Conditions
• ADHD
• ODD
• Conduct Disorder
• Learning Disabilities
• Substance Abuse
• Anxiety Disorders
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Individually
or
in combination
A Family History of
Bipolar 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
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Pediatric 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
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Summary
• 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
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Bipolar Disorder
Treatment Options
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Bipolar Management
•
•
•
•
•
•
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
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FDA Pediatric Labeling for BD
Brand name
Cibalith-S
Generic Name
Lithium citrate
Indicated Age
12 and older
12 and older
Eskalith
Lithium CO3
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
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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 welltolerated
• 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
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Treatment Algorithm for Mania/ Hypomania in
Children and Adolescents
Stage 1
Monotherapy
1A: Mixed/Manic
Quetiapine/
Aripiprazole/Risperidone
1B: Lithium/Valproate/
Olanzapine/Ziprasidone
Negative
response
Evaluate
Positive response
Continue
Positive response
Continue
Partial
response
Stage 2
Augmentation
2: Add mood stabilizer to atypical
or vice versa
Evaluate
Stage 3
2 drug
combinations
Partial response
or nonresponse
3: 2 mood stabilizers + 1 atypical or
2 atypicals + mood stabilizer
Kowatch RA et al. Clinical Manual for the Management of Bipolar Disorder in Children and Adolescents. Arlington, VA:
American Psychiatric Publishing, Inc; 2008.
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Lithium 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
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Management of Common Lithium Side Effects
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Divalproex 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
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Divalproex/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.
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Depression Switching to
Bipolar 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)
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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)
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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
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Expert Panel Question & Answer
• Treat or Refer?
• ADHD versus BD?
• When to add medications vs. switch
medications?
• Other questions?
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REMINDER:
Please fill out Unit I
evaluation
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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?
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Johnny’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
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Johnny’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
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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
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Johnny: 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
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Johnny’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
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Johnny’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
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Mood Stabilizer Toolbox
Mood
Stabilizer
Start at
Target Serum
Level
Monitor
Lithium
25-30
mg/kg/day
0.8-1.2
Meq/L
Renal/Thyroid
Function
Valproate
15-20
mg/kg/day
85-110
μg/mL
Liver/Pancreas/ PCOS
Plats.
Hyperammonemia
Carbamazepin
e
15-20
mg/kg/day
7-10
μg/mL
WBC/Plats.
Copyright © The REACH Institute. All rights reserved.
Watch Out
For
Dehydration
toxicity
CYP450 Interactions
Atypical Toolbox
Atypical
Antipsychotic
Start at
(mg/day)
Target
Dose
(mg/day)
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
Take with food,
Weight/Height/BMI Assess cardiac
ECG
risk factors
Ziprasidone
20-40
80-160
Olanzapine
5
5-20
Monitor
Watch Out
For
Weight/Height/BMI Choles/FAs
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RESOURCE SLIDE
FDA-Approved Bipolar Disorder
Treatments in Adults
Agents
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.
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RESOURCE SLIDE
DBPRCTs 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
DineenWagner et
al., (2006)
Oxcarbazepine
N=116; 7-18 y.o.;
Outpatient
Bipolar-I, manic
or mixed episode
Oxcarbazepine = PC (change in
YMRS)
DelBello et
al. (2005)
Topiramate
N=56; 6-17 y.o.;
Inpatient/outpatie
nt
Bipolar-I, manic
or mixed episode
Discontinued early when adult
studies failed to show efficacy; trend
toward improvement
BD
Divalproex ER = Placebo;
4 week study only; >50% dec YMRS;
DVP = 24%; Placebo = 28% ns;
UNPUBLISHED DATA
Abbott;
Unpublished
data
Divalproex ER
N=150; 10-17 y.o.
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RESOURCE SLIDE
Industry DB Placebo RCTs for Pediatric Bipolar
and Related Disorders: Atypicals
Study/
Sponsor
Ref
N
Olanz./
Lilly
Tohen
Am J
Psych.
161
Risper./
Janssan
AACAP
2007
Aripip/
BMS
Duration
(Days)
Dose
(mg/day)
Response
Rate
(YMRS)
Mean
Weight
Gain
(kg)
DBPCRT
2:1
21
10.4
+4.5
49%
3.66
+2.18
BPD I
Manic,
Mixed
DBPCRT
1:1:1
21
0.5-2.5
3-6
59%
63%
1.9
1.4
10-17
BPD I
Manic,
Mixed
DBPCRT
1:1:1
28
10
30
45%
64%
0.9
0.54
M
10-17
BPD I
Manic
DBPCRT
1:1:1
21
400
600
64%
58%
1.7
M
10-17
BPD I
Manic,
Mixed
DBPCRT
2:1
28
80-160
-13.83
(Zipras)
-8.61
(PBO)
-
Sites
Age
Range
Yr.
DX
26
10-17
BPD I
Manic,
Mixed
169
M
10-17
ACNP
2007
296
M
Que/
AstraZeneca
ACNP
2007
284
Zipras/
Pfizer
APA
2008
238
Design
Copyright ©2014The REACH Institute. All rights reserved.
RESOURCE SLIDE
Other DB Placebo RCTs for Pediatric Bipolar and
Related Disorders: Atypicals
Authors
DelBello et
al. (2002)
Treatment
Quetiapine as
adjunct to
Divalproex
Sample
Diagnosis
Results
N=30; 12-18 y.o.
Bipolar-I, manic
or mixed
episode
Significant decreases in YMRS
scores after 6 wks.
N=43; 8-17 y.o.
BD-I or II and
comorbid
ADHD?
Aripiprazole > Placebo for YMRS
Did not improve ADHD symptoms
UNPUBLISHED DATA
Luis Rohde,
Unpublished
Data
Aripiprazole
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RESOURCE SLIDE. Treatment Options for Pediatric
Bipolar Disorder: Selected Open Trials
Authors
Treatment
Sample
Diagnosis
Results
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. (1218); 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. (618); 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. (517); 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
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%)
ATYPICALS
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RESOURCE SLIDE
Higher 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
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RESOURCE SLIDE
DSM-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
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RESOURCE SLIDE
Mania vs. Hypomania
Criteria
Mood
Symptoms
Duration
Number of
Symptoms
Impairment
Manic Episode
Hypomanic Episode
“DISTINCT PERIOD OF
Abnormally & persistently
elevated, expansive, or
irritable mood.”
Same
7 days
At least 4 days
3 or more (4 if only irritable)
Same
Marked
Does not cause marked
impairment; unequivocal
change in functioning;
observable by others
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RESOURCE SLIDE
Variations in BP Illness Courses
Bipolar I Disorder:
Depression Followed by Mania
Bipolar I Disorder:
Single Manic Episode
Severe
Moderate
Mild
Time ---->
Mild
Time ---->
Euthymic
Depression
Euthymic
Depression
Moderate
Mild
Moderate
Severe
Time
Bipolar II Disorder: Depression
Followed by Hypomania
Mild
Moderate
Severe
Time
Mood Cycling Across A Lifetime
MANIA
Mania
Severe
DEPRESSION
Moderate
Mild
Depression
Euthymic
Mild
Moderate
Severe
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Time
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Mania
Mania
Severe
RESOURCE SLIDE
Distribution of Reported BD Age of Onset (yr.)
Goodwin & Jamison 2007
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RESOURCE SLIDE:
Mood Swings Quick Guide
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RESOURCE SLIDE: Rates of Disorder: Children
of Bipolar Parents vs. Control Parents
60
52
Bipolar Offspring
50
40
30
Control Offspring
29
26
24
21
17
% 20
11
10
4
11
0.8
11
4 3
3.6
0
Birmaher et al Arch Gen Psychiatry 2009:6
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RESOURCE SLIDE: Red Flag Symptoms
Symptom
Rages/Aggression
Not Bipolar
When told “no”, short, 5-10
min.
Possibly BP Disorder or
BP Spectrum
4-5 Xs/day, hours at a time, little
provocation, “Egg Shell” sign
Decreased Need for Initial/middle insomnia
Sleep
because of anxiety
3-4 day periods of “I only slept 4
hours and am feeling fine.”
Spontaneous Mood
Shifts
Silly/giddly for hours in the AM;
depressed and suicidal in the PM
Moody/angry around sibs
and parents
High Risk Behaviors Project X
Grandiosity
“I can get into college
somewhere with my 2.0
GPA”
Agitation with
Antidepressant/SSR Not if it resolves
Is
Risky Business
“I don’t need to go to college to
start the next Facebook”
Possibly, if manic SXs continue
after SSRI is stopped.
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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?
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RESOURCE SLIDE:
Pharmacologic Treatments for Pediatric Bipolar Disorder: A
Review & Meta-analysis. Liu HY, Potter MP, Woodword Y, et. al.
• 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
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Copyright © The REACH Institute. All rights reserved.
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
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RESOURCE SLIDE:
Mood Stabilizers vs. Antipsychotics
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RESOURCE SLIDE:
Mood Stabilizers
 Traditional
 New/Novel *
 Lithium
 Valproate
(Sodium
Divalproex)
 Carbamazepine







Gabapentin
Lamotrigine
Topiramate
Tiagabine
Oxcarbazepine
Levetiracetam
Zonisamide
* Not recommended for PCPs’ initiation
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