Lurasidone is approved for the treatment of bipolar depression both as monotherapy and adjunctive therapy with lithium or valproate (Li/VPA). The aim of these analyses was to evaluate the prevalence of treatment-emergent mania (TEM) and worsening of mania symptom severity in clinical trials of both adult and pediatric patients with bipolar depression treated with lurasidone.

In these post-hoc analyses, TEM and change in manic symptom severity as measured by the Young Mania Rating Scale (YMRS) were evaluated in two double-blind (DB), 6-week studies in adults of lurasidone monotherapy, 20–60 mg/d (n=161) and 80–120 mg/d (n=162) vs. placebo (n=162), and adjunctive therapy of lurasidone 20–120 mg/d + Li/VPA (n=179) vs. placebo + Li/VPA (n=161). Prevalence of TEM was also evaluated in a 6-month, open-label (OL) extension study of adults treated with lurasidone monotherapy (n=316) or adjunctive therapy (n=497). In pediatric patients (ages 10–17) TEM and change in manic symptoms was evaluated in a DB 6-week study of lurasidone monotherapy (n=173) vs. placebo (n=170) and in a 24-month OL extension study. TEM was defined as an adverse event of mania or hypomania and/or having a YMRS score =16 at 2 consecutive post-baseline weekly visits (or the final assessment) in short-term studies or 1 post-baseline monthly visit in long-term studies.

Adult studies: In short-term studies, TEM rates were comparable in patients treated with lurasidone monotherapy 20–60 mg/d (3.7%) and 80–120 mg/d (1.9%) vs. placebo (1.9%). TEM rates were also comparable in patients treated with lurasidone 20–120 mg/d (1.1%) adjunctive to Li/VPA vs. placebo + Li/VPA (1.2%). In the monotherapy study, significant reduction in YMRS score was observed at study endpoint for the 20–60 mg/d group compared to placebo (−1.9 vs. −1.3; p<0.05) with similar improvement relative to placebo in the 80–120 mg/d group. Change for YMRS score was comparable for lurasidone and placebo in the adjunctive study. In long-term studies, 1.3% of adult patients treated with lurasidone monotherapy (n=316) met criteria for mania, and 3.8% of patients on adjunctive lurasidone therapy (n=497) met TEM criteria. Pediatric studies: TEM rates were comparable in 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). Pediatric long-term studies: After two years of OL treatment with lurasidone, 5.2% of patients met TEM criteria. Mean change in YMRS total score from DB baseline to Month 24 continued to improve (−2.0).

Short-term and long-term treatment with lurasidone demonstrated significant improvement in manic symptoms and was not associated with an increased risk of TEM in either adult or pediatric patient populations compared to rates reported in clinical populations of patients.

Sunovion Pharmaceuticals Inc.