Response to risperidone for childhood mania is high, but metabolic effects are a concern

New research funded by the National Institute of Mental Health found that risperidone as a first-line treatment for childhood mania is more effective than other mood stabilizing medications. However, potentially serious metabolic effects associated with the atypical antipsychotic drug raise concerns about long-term treatment.

The study of 279 children and adolescents aged 6 to 15 years with bipolar I disorder (manic or mixed episode) conducted at 5 US sites revealed a response rate (measured by scores on the Clinical Global Impressions for Bipolar Illness Improvement-Mania scale) of 68.5% with 8 weeks of risperidone as first-line treatment compared with 35.6% for lithium and 24.0% with divalproex sodium. None of the participants had taken an antimanic medication before the study.

Among metabolic concerns, patients treated with risperidone gained a mean of 3.31 kg compared with a gain of 1.42 kg in patients treated with lithium and a gain of 1.67 kg for those treated with divalproex. The mean increase in body mass index also was greater in patients randomized to risperidone versus those randomized to lithium or divalproex.

Blood prolactin levels did not change in the lithium and divalproex groups but increased from 7.2 ng/mL at baseline to 44.8 ng/mL at week 8 in the risperidone-treated patients.

Lithium recipients had a significant increase in thyrotropin levels. Researchers called for monitoring of thyrotropin levels early in the treatment if lithium is used. Electrocardiographic changes in the lithium and divalproex groups also require monitoring.

Twice as many patients on lithium discontinued treatment compared with risperidone (32.2% vs 15.7%).

The response rates to low doses of risperidone suggest that clinicians can be conservative in their treatment therapies. However, because of the risk for diabetes, weight gain, and cardiovascular problems, safer and more effective treatments for childhood mania should be pursued.

The study objective was to determine which treatment for childhood bipolar disorder should be tried first. Lithium has been used for many years, but approval was based on studies in adults, whereas divalproex is a commonly prescribed anticonvulsant. Risperidone has been approved by the US Food and Drug Administration to treat mania in children aged older than 10 years.

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