To evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.

Patients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.

At baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).

In this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.

Sunovion Pharmaceuticals Inc.