Long-Term Treatment of Bipolar Disorder in Children

Karen Dineen Wagner, MD, PhD

Department of Psychiatry, University of Texas Medical Branch, Galveston

An increasing amount of evidence indicates that bipolar disorder in children has a chronic course. Geller and colleagues1 conducted a prospective 8-year follow-up study of 115 children with first-episode bipolar I disorder; although recovery rates from mania were 88%, the relapse rate was 73%. Of the 54 youths who were young adults by the end of the 8-year follow-up, 44% had a manic episode in adulthood, which demonstrates continuity between childhood and adulthood bipolar disorder. Therefore, children with bipolar disorder are likely to need long-term treatment.

Efficacy of Medication Treatment

Four atypical antipsychotics and lithium have FDA approval for the treatment of bipolar I disorder, mixed or manic, in youths (AV 1AV 1) .2–6 Aripiprazole, quetiapine, and risperidone are approved for youths aged 10 to 17 years, and olanzapine is approved for ages 13 to 17 years. Efficacy of these medications as monotherapy was demonstrated in double-blind, placebo-controlled trials7–10 ranging in duration from 3 to 4 weeks. Another atypical antipsychotic, ziprasidone, also was significantly superior to placebo as monotherapy for pediatric mania in a 4-week, double-blind, placebo-controlled trial.11

To date, the anticonvulsants divalproex ER,12 oxcarbazepine,13 and topiramate14 have not been shown to be significantly superior to placebo in acute treatment studies for youths with bipolar I disorder, mixed or manic. However, divalproex demonstrated significant efficacy compared with placebo in 1 study.15

Limited information exists on the efficacy of treatments for bipolar I disorder, depressed, in youths. A controlled trial16 of quetiapine did not demonstrate superiority to placebo. However, open-label acute studies of lamotrigine17 and lithium18 showed a reduction in depressive symptoms.

Although efficacy of medication treatment has been shown in acute treatment studies, minimal controlled data about long-term medication treatment in youth with bipolar disorder are available. Kowatch and colleagues19 found that 58% of children with bipolar disorder who were treated with 1 medication over 8 weeks required treatment with an additional medication during the 16-week extension phase. The response rate to combination treatment with 2 mood stabilizers was 80% for youths who did not respond to initial mood stabilizer monotherapy. Thus, children with bipolar disorder will often require medication combination treatment over time.

FDA-approved adjunctive treatments for children ages 10 years and older with bipolar I disorder are aripiprazole2 and quetiapine4 added to lithium or valproate. Other combinations have been evaluated as well. In an open-label study,20 the combination of lithium and divalproex sodium was shown to significantly reduce symptoms of mania and depression in youth with bipolar disorder by 8 weeks (P < .0001). In another open-label study,21 risperidone in combination with lithium or divalproex sodium showed significant improvement in manic and depressive symptoms in pediatric bipolar disorder (P < .001).

Lamotrigine monotherapy was shown to be effective in maintaining manic and depressive symptom control for 6 weeks after the discontinuation of the concurrent atypical antipsychotic.22In a maintenance study23 of youths stabilized on combination lithium and divalproex sodium over 20 weeks, relapse occurred within approximately 4 months after discontinuation of either medication. Current guidelines recommend that clinicians consider tapering medication after sustained remission of at least 12 to 24 consecutive months.24

Adverse Event Monitoring

Because children with bipolar disorder will likely receive medication treatment for at least a few years, monitoring for potential adverse events is essential. Atypical antipsychotics have been shown to have cardiometabolic risks in youths treated over a time period as brief as 12 weeks.25 Correll26 suggested a monitoring schedule to assess for cardiometabolic and extrapyramidal symptoms for youths treated with atypical antipsychotics (AV 2AV 2). Additionally, a 12-item list of behaviors to promote healthy lifestyles and prevent and manage weight gain may be useful for youths who have been prescribed psychotropic medication.27 Monitoring for suicidality is also important, particularly given the FDA warning regarding an increased risk of suicidal thoughts and behavior with antiepileptic medications.28 Clinicians should be aware of potential risks of pancreatitis and polycystic ovarian syndrome with divalproex29 and hypothyroidism with lithium.6

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Psychosocial Interventions

Psychoeducational psychotherapy as adjunctive treatment to medication has been shown to improve outcomes for children with bipolar disorder.30 The main goals of this treatment are to provide information about the illness and medications, promote skill building, and facilitate social support. Adjunctive child- and family-focused CBT delivered in a group format demonstrated improvement in children’s manic symptoms and psychosocial functioning.31 Main components of this treatment include establishing a routine, regulating one’s affect, positive thinking, reframing thoughts, problem-solving, exhibiting positive social interaction, and finding social support. Interpersonal and social rhythm therapy as adjunctive treatment has also shown preliminary evidence of decreasing manic and depressive symptoms in adolescents with bipolar disorder.32 The main aims of this treatment are to reduce interpersonal stress, improve social rhythms and sleep/wake cycles, and increase medication compliance.

Support groups, such as the Child and Adolescent Bipolar Foundation (CABF), Depression and Bipolar Support Alliance (DBSA), and National Alliance on Mental Illness (NAMI) Child and Adolescent Action Center may be beneficial resources for youths with bipolar disorder and their parents in the long-term management of this illness.

For Clinical Use

  • Be aware that children with bipolar disorder are likely to need long-term treatment
  • For pediatric bipolar disorder, 4 atypical antipsychotics and 1 mood stabilizer are FDA-approved for mixed or manic episodes, and 2 atypical antipsychotics are approved for adjunctive treatment
  • Vigilantly monitor children and adolescents for adverse events while they are taking psychotropic medications
  • Consider using psychosocial interventions in addition to pharmacotherapy to help improve young patients’ symptomatic and functional outcomes

Drug Names

aripiprazole (Abilify), divalproex (Depakote and others), lamotrigine (Lamictal and others), lithium (Lithobid and others), olanzapine (Zyprexa), oxcarbazepine (Trileptal and others), quetiapine (Seroquel), risperidone (Risperdal and others), topiramate (Topamax and others), valproate (Depacon and others), ziprasidone (Geodon)

Abbreviations

AIMS = Abnormal Involuntary Movement Scale,BMI = body mass index, CBT = cognitive-behavioral therapy, EKG = electrocardiogram, EPS = extrapyramidal symptoms, ER = extended release, ESRS = Extrapyramidal Symptom Rating Scale, FDA = US Food and Drug Administration, SAS = Simpson Angus Rating Scale

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References

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