MEASURE Resource Module

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MEASURE Resource Module
 
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Approved/Unapproved Use

• The following presentation may contain
  information concerning a use that has not been
  approved by the US Food and Drug Administration.
  Any unlabeled/investigational discussion of drugs
  will be disclosed during the presentation.

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Bipolar Disorder in Children and Adolescents
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Bipolar Disorders Seriously Disrupt Lives of
Children and Adolescents

• These disorders should be treated aggressively
• Increased rates of suicide attempts and
  completions
• Poorer academic performance
• Disturbed interpersonal relationships
• Increased rates of substance abuse
• Legal difficulties
• Multiple hospitalizations

Emslie GJ, Mayes TL. Biol Psychiatry.
2001491082-1090.
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Why Bipolar Disorder in Children and Adolescents
Is Difficult to Diagnose

• Low-base rate of disorder
• Epidemiologic studies suggest mania in about 1
  of the population
• A childs age influences symptom expression
• Clinical presentation of bipolar disorder in
  younger patients is variable
• Symptoms of mania overlap with other more common
  childhood disorders
• ADHD
• Conduct disorder
• Aggression
• Overlap with substance-use disorders
• Association with trauma and adversity
• Atypical response to adult treatment standards

Biederman J et al. Biol Psychiatry.
200048458-466. Emslie GJ, Mayes TL. Biol
Psychiatry. 2001491082-1090.
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Prepubescent and Early Adolescent Bipolar
Disorder Phenotype

• Age of subjects 10.9 2.6 years
• Current episode 3.6 2.5 years
• Age at onset 7.3 3.5 years
• N 93
• Mixed
• 55 (N 51)
• Psychotic
• 60 (N 56)
• Rapid cycling (4 cycles/year)
• 87 (N 81)
• Ultrarapid cycling (5365 cycles/year)
• 10 (N 9)
• Ultradian cycling (gt 365 cycles/year)
• 77 (N 72)

Geller B et al. J Child Adolesc Psychopharmacol.
200010157-164.
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Pediatric Bipolar Disorder Outcomes

• Prepubertal
• At 2 years, 65 were in remission and 55
  relapsed
• Conduct disorder predicts worse outcome at 1 year
• Intact family predicts recovery
• Adolescent
• 96 five-year remission rate, 44 relapse
• 100 one-year remission rate, 67 two-year
  relapse

Srinath S et al. Acta Psychiat Scand.
199898437-442.
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Characteristics Common to Pediatric Mania

• Most common characteristics of pediatric mania
• Severe, prolonged irritability
• Affective storms
• Prolonged and aggressive temper outbursts
• Mixed mania or rapid cycling (gt 70 of cases)
• High comorbidity with ADHD
• Chronic and unremitting course

Biederman J et al. Biol Psychiatry.
200048458-466. State RC et al. Am J Psychiatry.
2002159918-925.
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Comorbidity of Psychiatric Disorders in
Pediatric Bipolar Disorder
Bipolar Disorder
ADHD
ODD/CD
Tic Disorders
Learning Disorders
Depression/Anxiety Disorders
ADHD attention deficit hyperactivity
disorder CD conduct disorders ODD
oppositional defiant disorder
Pliszka SR. Pediatr Drugs. 20035741-750.
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Difference in Mania Criteria PEA-BP and ADHD
Patients
P lt 0.0001
PEA-BP (n 93)
ADHD (n 81)
CC (n 94)
100
89.3
86
90
80
71
70
60
50
Patients ()
39.8
40
30
13.6
20
9.9
6.2
4.9
10
1.1
1.1
0
0
0
Elated Mood
Grandiosity
Flight and/or Racing Thoughts
Decreased Need for
Sleep
DSM-IV Mania Criteria
PEA-BP Prepubertal early adolescent bipolar
disease phenotype ADHD Attention deficit
hyperactivity disorder CC Normal community
control group
Craney JL, Geller B. Bipolar Disord.
20035243-256.
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Poor Judgment SymptomsPEA-BP and ADHD Patients
100
90.3
P lt 0.0001
PEA-BP (n 93)
ADHD (n 81)
CC (n 94)
90
80
65.6
70
65.6
63.1
60
44.4
50
43
Patients ()
40
24.7
30
23.5
20
11.1
6.2
10
3.2
3.2
0
0
0
0
Total Poor Judgment
Hypersexuality
Daredevil Acts
Silliness
Uninhibited People Seeking
Items Used to Rate Poor Judgment Criterion
Craney JL, Geller B. Bipolar Disord.
20035243-256.
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Overlapping Mania SymptomsPEA-BP and ADHD
Patients
PEA-BP (n 93)
ADHD (n 81)
CC (n 94)
120
P lt 0.0002
100
97.9
96.8
96.3
100
95.1
93.6
81.5
Patients ()
80
71.6
60
40
20
11.7
11.7
3.2
2.1
0
Irritable Mood
Accelerated Speech
Distractibility
Increased Energy
DSM-IV Mania Criteria
Craney JL, Geller B. Bipolar Disord.
20035243-256.
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Prevalence of Rapid Cycling PEA-BP and ADHD
Patients
100
87.1
90
77.4
80
70
60
Patients ()
50
40
30
20
9.7
8.6
6.2
10
2.5
0
0
0
0
0
Total Rapid Cycling
4
5364
? 365
Rapid
Ultrarapid
Ultradian
(continuous)
Cycles Per Year
Craney JL, Geller B. Bipolar Disord.
20035243-256.
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Characteristics of Prepubertal and Early
Adolescent Bipolar Disease Phenotype
70
PEA-BP (n 93)
60.2
60
54.8
50.5
50
40
Patients ()
30
24.7
20
10
0
Mixed Mania
Total Psychosis
Grandiose Delusions
Suicidality
Craney JL, Geller B. Bipolar Disord.
20035243-256.
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Weight Change in AdolescentsOlanzapine vs
Risperidone vs Haloperidol
12
11
10
N 50 P lt 0.01
9
8
7
Mean Proportional Weight Change ()
Olanzapine
6
Risperidone
5
Haloperidol
4
3
2
1
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Week
Ratzoni G et al. J Am Acad Child Adolesc
Psychiatry. 200241337-343.
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Suggested Dosages of Atypical Antipsychotics
forBipolar Disorder in Children and Adolescents
Generic Name
Starting Dose (mg/d)
Target Dose (mg/d)
Clozapine Olanzapine Quetiapine Risperidone Zipras
idone Aripiprazole
2550 2.55 50100 0.51 2040 2.55
200400 1020 400600 24 80120 1530
The FDA has not approved a specific indication
for these agents for use in children and
adolescents
Adapted from Kowatch RA, DelBello MP. CNS Spectr.
20038278.
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Bipolar Disorder and Pregnancy

• Women in childbearing years may be exposed to
  potentially teratogenic mood-stabilizing agents
• First episode of mania typically occurs before
  age 30
• Some mood stabilizers can alter the metabolism of
  oral contraceptives
• Pregnancy can
• Exacerbate bipolar symptoms
• Alter pharmacokinetics of mood-stabilizing drugs
• High levels of lithium, valproic acid, and
  carbamazepine and low levels of folate in
  maternal blood are risk factors for teratogenesis
  
• Lithium, valproic acid, and carbamazepine should
  be avoided if possible, especially during the
  sensitive phase of organogenesis (days 18 to 55
  after conception)

Burt VK et al. Bipolar Disord. 200462-13. Iqbal
MM et al. South Med J. 200194304-322.
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Risks to Mother and Fetus May Be Reduced

• Prenatal counseling at least 3 months before
  conception
• Periconceptional use of multivitamins with folate
• Treatment during pregnancy should be avoided if
  clinically feasible
• Particularly during the first trimester
• Monotherapy is preferable
• Higher risk of congenital malformation associated
  with combination therapy
• If treatment is pursued, it is important to treat
  with minimal effective dose
• Minimal effective dose should be estimated by
  using lowest dose that has historically kept
  patient stable and well
• ECT may be used for immediate stabilization
• More than 300 reports of ECT used during
  pregnancy with no clear evidence of teratogenic
  effects

Burt VK et al. Bipolar Disord. 200462-13. Iqbal
MM et al. South Med J. 200194304-322.
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Antimanic Agents Teratogenic Risk

• Classification Category
• Lithium D
• Valproic acid D
• Carbamazepine C
• Lamotrigine C
• Haloperidol C
• Chlorpromazine C
• Aripiprazole C
• Clozapine B
• Quetiapine C
• Risperidone C
• Olanzapine C
• Ziprasidone C
• Clonazepam C

• The FDA has derived a system of pregnancy
  categories based on the degree to which
  available information has ruled out risk to the
  fetus balanced against the drugs potential
  benefits to the patient
• A controlled studies show no risk
• B no evidence of risk in humans
• C risk cannot be ruled out
• D positive evidence of risk
• X contraindicated in pregnancy

Iqbal MM et al. South Med J. 200194304-322. Yonk
ers KA et al. Am J Psychiatry. 2004161608-620
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Bipolar Disorder and PregnancyPostpartum and
Breastfeeding

• The postpartum period is associated with high
  risk of relapse
• Regardless of whether a mood episode occurred
  during pregnancy
• Between 40 and 67 female bipolar patients
  experience a postpartum mood episode within 1
  month of delivery
• Postpartum psychosis
• The most severe form of postpartum mood disorders
• Women with bipolar disorder have 100-fold higher
  risk of developing postpartum psychosis than
  controls
• Usually occurs within 3 weeks of childbirth
• Typically presents with delusions
• Virtually all medications are secreted in breast
  milk
• Breastfeeding almost guarantees sleep deprivation
• Frequent nighttime awakening can cause or
  contribute to mood destabilization

.
Burt VK et al. Bipolar Disord. 200462-13.