Objectives: To review key aspects of the lurasidone bipolar development program.
Methods: The efficacy and safety of lurasidone was evaluated for the treatment of bipolar I depression, based on results from 3 randomized, double-blind, placebo-controlled, 6-week trials (lurasidone, N=691; placebo, N=502). In a 6-week monotherapy trial, patients were assigned to one of two fixed-flexible dose ranges of lurasidone (20-60 mg/d or 80-120 mg/d); in the two 6-week adjunctive trials, patients received flexible doses of lurasidone (20-120 mg/d) or placebo, adjunctive with lithium or valproate. Patients (N=813) completing the three 6-week trials continued in a 6-month open-label extension study.
Results: In the monotherapy study, treatment with lurasidone was associated with significantly greater improvement in the Montgomery Asberg Depression Rating Scale (MADRS) from Weeks 2-6. Significantly greater improvement was also observed on secondary efficacy measures. Treatment with lurasidone was associated with significantly greater improvement in the MADRS at Weeks 3-6 in the first adjunctive study, and at Weeks 2-5 (but not at Week 6) in the second adjunctive study. The most frequently reported adverse events in the short-term studies were nausea, somnolence and akathisia. During 6 months of continued treatment, sustained improvement in depressive symptoms was observed on lurasidone, with minimal effects on weight or metabolic parameters.
Conclusions: Lurasidone, both as monotherapy and as adjunctive therapy with lithium or valproate, appears to be an effective treatment for bipolar I depression with a favorable benefit-risk profile in short- and longer-term treatment.