Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies

Abstract Introduction Early onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old). Methods Data from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1 st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2 nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm. Results The safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P<0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P<0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin. Conclusions In this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin. Funding Servier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.