Pediatric Bipolar Affective Disorder Medication

  • Author: Bettina E Bernstein, DO; Chief Editor: Caroly Pataki, MD   more...
 
Updated: May 21, 2012
 

Medication Summary

Mood stabilizers, such as lithium carbonate, sodium divalproex, and carbamazepine, have traditionally been the mainstays of treatment of patients with bipolar disorder. However, atypical antipsychotics are increasingly used in bipolar disorder, with or without psychotic symptoms. This class of medications includes risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone, and clozapine. In addition, benzodiazepines may be used to improve sleep and to modulate agitation during hospitalization.

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Mood stabilizers

Class Summary

Mood stabilizers are indicated for control of manic episodes occurring in bipolar disorder. They include lithium carbonate, valproic acid or sodium divalproex, and carbamazepine.

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Lithium (Lithobid)

 

Lithium is considered a first-line agent for long-term prophylaxis in bipolar illness, especially classic bipolar disorder with euphoric mania. It is also used to treat acute mania, though it cannot be up titrated to an effective level as quickly as valproic acid can. Evidence suggests that lithium, unlike any other mood stabilizer, may have a specific antisuicide effect. Monitoring of blood levels is critical with this medication.

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Anticonvulsants

Class Summary

Anticonvulsants have been effective in preventing mood swings associated with bipolar disorder.

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Valproic acid (Depacon, Depakene, Depakote)

 

Valproic acid has proven effectiveness in treating and preventing mania. It is classified as a mood stabilizer and can be used alone or in combination with lithium. It is useful in treating rapid-cycling bipolar disorders and has been used to treat aggressive or behavioral disorders. A combination of valproic acid and valproate has been effective in treating persons in manic phase, with a success rate of 49%.

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Carbamazepine (Equetro)

 

Carbamazepine's anticonvulsant action may involve depressing activity in the nucleus ventralis anterior of the thalamus, reducing polysynaptic responses and blocking posttetanic potentiation. Carbamazepine reduces sustained, high-frequency, repetitive neural firing. It is a potent enzyme inducer that can induce its own metabolism. Because of potentially serious blood dyscrasias, weigh benefit and risk before therapy.

Therapeutic plasma levels are 4-12 µg/mL for analgesic and antiseizure response. Serum levels peak in 4-5 h. Serum half-life is 12-17 h with repeated doses. Carbamazepine is metabolized in the liver to its active metabolite (epoxide derivative) with a half-life of 5-8 h. Metabolites are excreted in feces and urine.

Carbamazepine is effective in cases that do not respond to lithium therapy. It has been effective in treating rapid-cycling bipolar disorder.

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Atypical Antipsychotics

Class Summary

Atypical antipsychotics are being used increasingly for treatment of both acute mania and mood stabilization.

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Aripiprazole (Abilify, Abilify Discmelt)

 

Aripiprazole is an atypical antipsychotic that is approved for bipolar disorder in children aged 10-17 years. It can be used as monotherapy or adjunctively with lithium or valproate. For children younger than 10 years, the safety and efficacy has not been established. It is a partial dopamine D2 and serotonin 5HT1A agonist, and it antagonizes serotonin 5HT2A.

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Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

 

Risperidone binds dopamine D2-receptor with a 20 times lower affinity than it has for 5-HT2 receptor. It is indicated for short-term (3-wk) treatment of acute mania associated with bipolar disorder. It may be used alone or combined with lithium or valproate. Risperidone is approved for bipolar mania in children aged 10-17 years.

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Quetiapine (Seroquel, Seroquel XR)

 

Quetiapine is indicated for acute treatment of manic episodes that are associated with bipolar I disorder. It is approved for bipolar mania in children aged 10-17 years. Quetiapine may act by antagonizing dopamine and serotonin effects. It is a newer antipsychotic used for long-term management. Improvements over earlier antipsychotics include fewer anticholinergic effects and less dystonia, parkinsonism, and tardive dyskinesia.

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Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprew)

 

Olanzapine's mechanism of action for acute manic episodes associated with bipolar I disorder is unknown. It is approved by the US Food and Drug Administration (FDA) for adolescents with bipolar I disorder. It is available in tablet, oral disintegrating tablets (Zyprexa, Zydis), and intramuscular (IM) dosage forms. It is approved for children aged 13 years and older.

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Ziprasidone (Geodon)

 

Indicated for acute bipolar mania, including manic and mixed episodes. Antagonizes dopamine D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, alpha1 adrenergic. Has moderate antagonistic effect for histamine H1. Moderately inhibits reuptake of serotonin and norepinephrine. Although effective for bipolar disorder, the mechanism of action in bipolar disorder is unknown.

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Contributor Information and Disclosures
Author

Bettina E Bernstein, DO  Consultant at Resources for Human Development

Bettina E Bernstein, DO is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry and American Psychiatric Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Caroly Pataki, MD  Professor of Clinical Psychiatry and Behavioral Sciences, Department of Psychiatry, Division Chair, Child and Adolescent Psychiatry, Keck School of Medicine of the University of Southern California

Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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Table 1. Characteristic Behaviors Associated With Bipolar Disorder, ADHD, and Conduct Disorder
Behavior Bipolar Disorder ADHD Conduct Disorder
Self-esteemInflatedInflated and/or deflatedInflated and/or deflated
PleasureEuphoric in mania



Dysphoric in mixed or depressed state



Often dysphoric or euthymicPleasure in violating societal norms, especially if not caught
AttentionDistractibleDistractibleNormal to vigilant
HyperactivityGoal directedUnproductiveGoal directed
SleepEpisodic disturbances such as decreased need in maniaChronic poor sleep; often late bedtimesNot known to be disrupted except with substance abuse
SpeechPressured or rapid in mania; slow in depressionOften rapid; may be pressuredMay be normal rate
ImpulsivityExternally driven; reactionaryInternally drivenMay have predatory or reactionary acts
SocialOften goodOften poorOften poor
AcademicOften goodOften poorOften poor
Psychomotor activityAgitated in mania or mixed states; retarded in depressed statesChronically agitatedEasily agitated
ADHD—attention deficit/hyperactivity disorder.
Table 2. Medications for Pediatric Bipolar Disorder: Common Adverse Effects and Special Concerns
Medication Common Adverse Effects Pediatric Doses Special Concerns
Lithium carbonate (Lithobid)GI distress, lethargy or sedation, tremor, enuresis, weight gain, alopecia, cognitive blunting10-30 mg/kg/d; dose must be adjusted by monitoring serum level and patient response; up-titrate on twice-daily scheduleHypothyroidism, diabetes insipidus, toxic in dehydration, polyuria, polydipsia, renal disease; drug-drug interactions and sodium intake may alter therapeutic serum levels



Approved for patients 12 y and older



Sodium divalproex/valproic acid (Depakote, Depakene)Sedation, platelet dysfunction, liver disease, alopecia, weight gain15-30 mg/kg/d; dose must be adjusted by monitoring serum levels; up-titrate on twice- or thrice-daily scheduleElevated liver enzymes or liver disease, drug-drug interactions, bone marrow suppression



Approved for patients 12 y and older



Aripiprazole (Abilify, Abilify Discmelt)Less likely to cause prolactinemia than risperidone; may cause Stevens-Johnson syndrome; as with other atypical antipsychotics, may cause tardive dyskinesia, dystonia, parkinsonism, hyperglycemia; use with caution in seizure disorders and cardiac disorders, including problems with cardiac contractility and electrical activity 2 mg once daily can be increased to 5 mg, 10 mg, 15 mg, to a maximum of 30 mg to start



titrate upwards at weekly to bimonthly intervals



levels may need to be adjusted in patients who are concurrently receiving lamotrigine, topiramate, Depakote, lithium, or other serotonin-norepinephrine reuptake, selective serotonin reuptake, or cytochrome P450 inhibitors



Do not administer if there is an unstable seizure disorder



Approved for patients 12 y and older



Carbamazepine (Equetro)Suppressed WBCs, dizziness, drowsiness, rashes, liver toxicity (rare)10-20 mg/kg/d; dose must be adjusted by monitoring serum blood levels; up-titrate on twice-daily scheduleDrug-drug interactions, bone marrow suppression
Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)Weight gain, sedation, orthostasis0.25 mg bid or 0.5 mg at bedtime initially; titrate as tolerated to target dosage of 2-4 mg/d; not to exceed 6 mg/dGalactorrhea, extrapyramidal symptoms



Approved for patients 10 y and older



Quetiapine (Seroquel, Seroquel XR)Sedation, orthostasis, weight gain50 mg bid initially; titrate as tolerated to target dosage of 400-600 mg/dDecrease dosage with hepatic impairment, may cause neuroleptic malignant syndrome or hyperglycemia



Approved for patients 10 y and older



Olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv)Weight gain, dyslipidemia, sedation, or orthostasis2.5-5 mg at bedtime initially; titrate as tolerated to target dosage of 10-20 mg/dMetabolic syndrome, extrapyramidal symptoms
Clonazepam (Klonopin)Sedation, abnormal coordination, ataxia0.01-0.04 mg/kg/d PO at bedtime or divided bidCaution with renal/hepatic impairment and asthma
Fluoxetine (Prozac)Headache, nausea, insomnia, anorexia, anxiety, asthenia, diarrhea, somnolence10 mg PO qd; may consider increasing to 20 mg/d after 1 wkLong half-life; potential to exacerbate manic symptoms when not coadministered with an antimanic or mood-stabilizing agent
Ziprasidone (Geodon)Akathisia, nauseaOff-label: 20 mg PO at bedtime; can increase to 40 mg (not to exceed 60 mg), usually in 2 divided doses for childrenRisk of sudden cardiac death due to torsades des pointes due to prolonged QT prolongation, which makes this medication undesirable for individuals with a family history of cardiac sudden death related to cardiac conduction abnormalities
WBC—white blood cell.
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