Risperidone in combination with mood stabilizers: A 10-week continuation phase study in bipolar I disorder

Background: Combination therapy (risperidone and a mood stabilizer) for patients with a history of bipolar disorder (DSM-IV) and hospitalized for treatment of a manic episode was assessed in a 13-week study. Method: Subjects received flexible doses of a mood stabilizer (lithium or divalproex) plus placebo, risperidone, or haloperidol in a 3-week double-blind study. They could then enter a 10-week open-label study during which they received risperidone combined with a mood stabilizer. Results: Of the 156 patients enrolled in the 3-week study, 85 entered the 10-week open-label extension, of whom 48 completed 10 weeks of treatment. The mean ± SE doses of risperidone were 3.8 ± 0.3 mg/day during the 3-week study and 3.1 ± 0.2 mg/day during the 10-week study. At double-blind endpoint, mean reductions in Young Mania Rating Scale (YMRS) scores were significantly greater in patients receiving risperidone plus mood stabilizer than in those receiving placebo plus mood stabilizer (-14.3 vs. -8.2, p < .001). Further significant (p < .001) reductions were seen during the 10 weeks of treatment with risperidone plus mood stabilizer. Symptom remission (YMRS score ≤ 12) was seen in 38 patients (79%) at the end of the 10-week study. Scores on the Brief Psychiatric Rating Scale, Hamilton Rating Scale for Depression, and Clinical Global Impressions scale improved significantly (p < .05) during both the 3-week and 10-week studies. Treatment was well tolerated, and modest weight gain was observed during the 13-week study period. Conclusion: The combination of risperidone and a mood stabilizer was efficacious and well tolerated in the continuation treatment of patients initially hospitalized for the management of an acute manic episode.