Lurasidone adjunctive to lithium or valproate for prevention of recurrence in patients with bipolar I disorder

Introduction Information is not available on the maintenance efficacy of lurasidone in bipolar disorder. Objectives/aims To evaluate the recurrence prevention efficacy of lurasidone plus lithium (Li) or valproate (VPA) for the maintenance treatment of bipolar disorder. Methods Patients with bipolar I disorder received up to 20 weeks of open-label lurasidone (20–80 mg/d) plus Li or VPA. Patients who achieved consistent clinical stability were randomized to 28 weeks of double-blind treatment with lurasidone (20–80 mg/d) or placebo, plus Li or VPA. Results A total of 496 patients met stabilization criteria and were randomized to adjunctive lurasidone vs. placebo. Fewer patients in the lurasidone group had recurrence of any mood episode compared with the placebo group, with a hazard ratio of 0.71 ( P  = 0.078). In pre-planned secondary analyses, recurrence rates were significantly lower for the lurasidone group treated with a modal open-label dose of 80 mg/d (hazard ratio [HR], 0.35; P  = 0.020); when patients presented with an index episode of depression (HR = 0.57; P  = 0.039); and when outcome was time-to-all-cause discontinuation (HR = 0.72; P  = 0.034), or time-to-recurrence based on symptom severity criteria (HR = 0.53; P  = 0.025). Conclusions In patients stabilized on lurasidone plus Li or VPA, continued treatment was associated with non-significant reduction in risk of recurrence of any mood disorder (primary). Consistent with dose-response effects observed during acute treatment of bipolar depression, risk of recurrence on lurasidone was significantly reduced after open-label treatment with the 80 mg/d dose, and in the 20–80 mg/d dose in patients presenting with an index episode of depression. Clinicaltrials.gov: NCT01358357 . Sponsored by Sunovion Pharmaceuticals Inc.