Introduction: To evaluate the investigational use of risperidone long-acting injectable (LAI) monotherapy vs placebo for prevention of mood episodes in patients with bipolar I disorder.

Methods: Patients aged 18–65 years diagnosed as acutely manic, mixed, or stabilized on risperidone or another medication entered the screening period. The study consisted of a 3-week open-label oral risperidone treatment period (for patients not already stabilized on risperidone), a 26-week open-label stabilization period with risperidone LAI and a double-blind treatment period (placebo or risperidone LAI 12.5, 25, 37.5 and 50 mg every 2 weeks, for up to 24 months). Primary efficacy variable was time-to-relapse to any mood episode during the double-blind period.

Results: Of the 501 patients who received open-label risperidone LAI, 303 (60%) maintained symptom remission throughout the 26-week stabilization period. They were randomized 1:1 to continue their maintenance dose (n=154) or placebo (n=149);
77% of patients received a dose of 25 mg. Time to relapse to any mood episode was signifi cantly longer in the risperidone LAI group compared with the placebo group (p<0.001). The time by which 25% of the patients relapsed to any mood episode was 173 days in the risperidone LAI group and 82 days in the placebo group. Adverse events that occurred more frequently with risperidone LAI than placebo (=3% difference) were depression (6 vs 2%) and weight increase (5 vs 1%).

Discussion: This is the fi rst controlled study of a long-acting atypical antipsychotic to demonstrate effi cacy as monotherapy in relapse prevention of mood episodes in patients with bipolar I disorder. Risperidone LAI was associated with a signifi cant
reduction in the rate of relapse and a delay in the time to relapse, and had a tolerable safety profile.