Rapid Antimanic Effect of Risperidone Monotherapy: A 3-Week Multicenter, Double-Blind, Placebo-Controlled Trial

OBJECTIVE: This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic episode (baseline Young Mania Rating Scale score ≥20) were randomly assigned to 3 weeks of treatment with risperidone (flexible dose: 1-6 mg day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale. Secondary efficacy measures included the Clinical Global Impression (CGI) severity rating and scores on the Montgomery-Åsberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Global Assessment Scale (GAS). Safety assessments consisted of monitoring adverse events, vital signs, electrocardiogram and laboratory results, and scores on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose of risperidone was 4.1 mg day. Improvement in mean Young Mania Rating Scale total score (adjusted for covariates) was significantly greater in the risperidone than in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5], respectively), with significant between-group differences seen as early as 3 days after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements in CGI severity ratings and scores on the Montgomery-Åsberg Depression Rating Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater among patients receiving risperidone than those given placebo. The most common adverse event reported among risperidone patients was somnolence. While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone, mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action. Risperidone was well tolerated by patients in this study.