Risperidone (Risperdal, Janssen) may be more effective than lithium or divalproex sodium (Depakote, Abbott) for the initial treatment of childhood mania but it could lead to potentially serious metabolic side effects, including weight gain, according to a study published online January 2, in the Archives of General Psychiatry.

The Treatment of Early Age Mania (TEAM) study was conducted by Barbara Geller, MD, Department of Psychiatry, Washington University, St Louis, Mo., and colleagues to fill the gap in comparative pharmacological research investigating appropriate interventions for child psychiatry outpatients.

TEAM investigators sought to determine which medication to give first to medication-naive subjects through a controlled, randomized, no-patient-choice, 8-week protocol. They recruited 290 children, ages 6 to 15 years from 5 US sites between 2003 and 2008.

The children had been diagnosed with DSM-IV bipolar I disorder (manic or mixed phase). Each child was randomly assigned, stratified by age group (6-12 vs 13-15 years) and by the presence or absence of mixed mania, psychosis, and daily rapid cycling, to either medication-naive (n=290) or partial/nonresponder categories (n=89). Blinded, independent evaluators conducted all baseline and end-point assessments.

Patients received a titrated schedule of lithium, divalproex sodium, or risperidone. The medications were begun at low doses and increased weekly—only if the child had minimal-to-no response, and no dose-limiting adverse effects—to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg).

The investigators found that risperidone was significantly superior for acute treatment of pediatric mania to lithium and divalproex sodium on the primary outcome measure -- the Clinical Global Impressions for Bipolar Illness Improvement–Mania. And response rates at relatively low doses of risperidone suggest that clinicians can be more conservative with the medication.

Risperidone also was tolerated much better than lithium, which the authors noted by the significantly higher discontinuation rates in the lithium group.

Although the response rate was significantly higher in the risperidone group, the investigators noted that weight gain, BMI increase, and presence of hyperprolactinemia were significantly worse.

“These metabolic factors and electrocardiographic changes observed in the lithium and divalproex sodium groups require monitoring,” they wrote.

“The decreased lipid levels in the divalproex sodium group are consistent with the salutatory effects of valproate preparations on lipid levels in epileptic children. The significantly increased thyrotropin levels in subjects treated with lithium, although not to out-of-range levels, argues for monitoring thyrotropin levels early in treatment.”