Objectives: To evaluate the efficacy and safety of lurasidone adjunctive with lithium (Li) or valproate (VPA) in bipolar I depression.
Methods: Data were pooled from 2 studies in which patients with bipolar I depression received 6 weeks of double-blind treatment with lurasidone 20-120 mg/d (N=355) or placebo (N=327), adjunctive with Li or VPA. The primary and key secondary efficacy measure were, respectively, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression, Bipolar - Severity of Illness Scale (CGI-BP-S), analyzed by a mixed-effects model for repeated measures (MMRM). Results: At Week 6, treatment with lurasidone (vs placebo) was associated with improvement in the mean MADRS (-14.4 vs -11.9; P=0.003), CGI-BP-S (-1.7 vs -1.3; P=0.001), and most secondary efficacy measures. Responder rates (MADRS reduction ≥50%) were significantly higher with lurasidone vs placebo (48% vs 37%; P=0.002). Minimal changes were observed for lurasidone (vs placebo) in mean weight (+0.1 vs +0.2 kg), median total cholesterol (-4.0 vs -1.0 mg/dL), triglycerides (+4.0 vs -2.0 mg/dL), and glucose (0.0 vs 0.0 mg/dL). Discontinuation rates due to adverse events were similar for lurasidone vs placebo (5.8% vs 4.8%); adverse events (≥5% incidence) were nausea (13.9% vs 10.2%), Parkinsonism (12.8% vs 8.1%), somnolence (11.4% vs 5.1%), and akathisia (10.8% vs 4.8%).
Conclusions: Results of this pooled analysis demonstrated that lurasidone, adjunctive with and Li or VPA, was an effective treatment of bipolar depression, with a low rate of discontinuation due to adverse events, and minimal effect on weight or metabolic parameters.