Effect of Lurasidone on Manic Symptoms and Treatment-Emergent Mania in Children and Adolescents with Bipolar Depression

Background: The aim of these analyses was to assess the effect of lurasidone on manic symptoms and treatment-emergent (TE) mania in pediatric patients with bipolar depression.

Methods: Patients (ages 10-17) were randomized, double-blind (DB) to 6-weeks of lurasidone 20-80 mg/d (n=173) or placebo (n=170). Study completers were eligible to enter a 24-month open-label (OL) extension study of lurasidone (20-80 mg/day). Manic symptoms were measured using the Young Mania Rating Scale (YMRS). TE-mania was defined as an adverse event of mania/hypomania or having a YMRS score ≥16 at 2 consecutive post-baseline weekly visits in short-term studies, or 1 post-baseline monthly visit in the OL extension.

Results: 305 patients entered the extension study; 195 and 93 completed 52 and 104 weeks of treatment, respectively. TE-mania rates were comparable in pediatric patients treated with lurasidone vs. placebo (1.7% vs. 2.3%). LS mean reduction in symptoms of mania from baseline to week 6 was significantly greater for lurasidone vs. placebo on YMRS score (-2.0 vs. -1.1; p < 0.05). After two years of open-label treatment with lurasidone, 5.2% of patients met TE-mania criteria. Mean change in YMRS total score from double-blind baseline to Month 24 continued to improve (-2.0).

Conclusion: During 6 weeks of treatment, TE-mania rates were comparable for both lurasidone and placebo groups. Over 2 years of lurasidone therapy, TE-mania was only observed in a small proportion of patients. Both short- and long-term treatment with lurasidone demonstrated improvement in manic symptoms in this patient population.