Efficacy and Safety of Lurasidone in Children and Adolescents With Bipolar I Depression: A Double-Blind, Placebo-Controlled Study

ObjectiveTo evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression.MethodPatients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change from baseline to week 6 in the Children’s Depression Rating Scale–Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures analysis.ResultsA total of 347 patients were randomized and received at least 1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (−21.0 versus −15.3; p < .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters.ConclusionIn this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters.Clinical trial registration information—Lurasidone Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369. To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression. Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change from baseline to week 6 in the Children’s Depression Rating Scale–Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures analysis. A total of 347 patients were randomized and received at least 1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (−21.0 versus −15.3; p < .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters. In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters.