Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study.

OBJECTIVE Few studies have been reported that support the efficacy of adjunctive therapy for patients with bipolar I depression who have had an insufficient response to monotherapy with mood-stabilizing agents. The authors investigated the efficacy of lurasidone, a novel antipsychotic agent, as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression. METHOD Patients were randomly assigned to receive 6 weeks of double-blind adjunctive treatment with lurasidone (N=183) or placebo (N=165), added to therapeutic levels of either lithium or valproate. Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP), respectively. RESULTS Lurasidone treatment significantly reduced mean MADRS total score at week 6 compared with the placebo group (-17.1 versus -13.5; effect size=0.34). Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in CGI-BP depression severity scores compared with placebo (-1.96 versus -1.51; effect size=0.36) as well as significantly greater improvement in anxiety symptoms and in patient-reported measures of quality of life and functional impairment. Discontinuation rates due to adverse events were 6.0% and 7.9% in the lurasidone and placebo groups, respectively. Adverse events most frequently reported for lurasidone were nausea, somnolence, tremor, akathisia, and insomnia. Minimal changes in weight, lipids, and measures of glycemic control were observed during treatment with lurasidone. CONCLUSIONS In patients with bipolar I depression, treatment with lurasidone adjunctive to lithium or valproate significantly improved depressive symptoms and was generally well tolerated.