Objective: To evaluate the longer-term safety and tolerability of lurasidone in bipolar I depression.
Methods: Patients completing 6 weeks of placebo-controlled treatment with either lurasidone monotherapy (1 study) or lurasidone adjunctive therapy with lithium or valproate (2 studies), were treated for 6 months with flexible doses of lurasidone, 20-120 mg/d in this open-label extension study (N=813). Safety endpoints were analyzed as change from double-blind baseline to month 6 (observed case analysis). Efficacy endpoints were secondary, and included the Montgomery-Asberg Depression Rating Scale (MADRS).
Results: 68% of patients completed the study. Adverse events (AE; incidence ≥5%) for the monotherapy and adjunctive therapy groups, respectively, were 6.0% and 9.5% for akathisia, 11.1% and 5.6% for headache, 7.3% and 7.8% for nausea, 6.3% and 6.4% for insomnia, and 4.4% and 6.6% for anxiety; 7.0% and 8.7% discontinued due to an AE. Mean change in weight at month 6, for the monotherapy and adjunctive therapy groups, respectively was +0.45 kg and +0.90 kg; and median change was 0.0 mg/dL and -1.5 mg/dL for total cholesterol, +6.0 mg/dL and +8.0 mg/dL for triglycerides, and 0.0 mg/dL and +1.0 mg/dL for glucose. The incidence of treatment-emergent mania was 1.3% in the monotherapy treatment subgroup and 3.8% in the adjunctive subgroup. Mean change on the MADRS was -6.9 in the monotherapy group and -6.5 in the adjunctive therapy group.
Conclusion: Six months of treatment with lurasidone was safe and well-tolerated, with minimal effect on weight and metabolic parameters, and with sustained improvement in MADRS.