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Bipolar I Disorder in Children: Which Treatment Works Best?
Am Fam Physician. 2012 Nov 1;86(9):848-853.
Background: Although antipsychotic medications are often prescribed for childhood mania, few trials have examined their benefits and adverse effects in this population. Several randomized trials have reported that atypical antipsychotics are helpful for treating mania in adolescents, but these trials have not included children younger than 10 years or compared the relative benefits of different medications. Geller and colleagues conducted a randomized controlled trial to determine the most effective medication for treating mania in children and adolescents.
The Study: In the Treatment of Early Age Mania study, outpatients six to 15 years of age were randomized to receive lithium, divalproex (Depakote), or risperidone (Risperdal). Eligible participants had a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of bipolar I disorder (manic or mixed episode) for at least four consecutive weeks at study enrollment, with a Children's Global Assessment Scale (CGAS) score of 60 or less. Persons with coexisting attention-deficit/hyperactivity, oppositional defiant, or conduct disorder were allowed to participate because these are common comorbidities in childhood mania. Those with a history of schizophrenia, pervasive developmental disorder, major medical or neurologic disease, substance abuse, or any previous psychotropic drug use (including atypical antipsychotics, lithium, and anticonvulsants) were excluded. Concurrent use of most psychiatric medications was not permitted during the study, except for maintenance doses of methylphenidate (Ritalin) and amphetamine preparations.
Participants were started at low doses of their study medication, with titration upward if there was minimal or no improvement based on weekly assessments using the Clinical Global Impressions for Bipolar Illness Improvement–Mania (CGI-BP-IM) scores. Up to 10 tablets of chlorpromazine (25 mg) were allowed as a rescue medication during the first four weeks. The primary outcome measure was improvement in the CGI-BP-IM score over an eight-week period.
Results: The study analyzed 89 persons who received risperidone, 90 who received lithium, and 100 who received divalproex. There was no significant difference between groups regarding medication adherence rates, stimulant medication use, the need for rescue medication, or discontinuance rates from adverse events. Overall, those treated with risperidone had a significantly higher response rate (68.5 percent) than those treated with lithium (35.6 percent) or divalproex (24.0 percent). There was no significant difference in response rates between lithium and divalproex. Similar response rates were found during subgroup analysis based on age (six to 12 years versus 13 to 15 years), associated psychosis, and the presence or absence of concurrent stimulant use. The risperidone group also had significantly greater improvement in CGAS scores and absence of mania by DSM-IV criteria at the end of the study, compared with the lithium and divalproex groups. No serious medication-related adverse events were identified, although participants in the risperidone group did have significantly greater weight gain than those in the other groups.
Conclusion: Risperidone is significantly more effective than lithium or divalproex in the initial management of mania in children. However, it is also associated with greater weight gain, which may raise concerns about its use for long-term management in children.
Geller B, et al. A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry. May 2012;69(5):515–528.
Copyright © 2012 by the American Academy of Family Physicians.
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