Lurasidone for bipolar I depression with comorbid anxiety symptoms: Post-hoc-analysis of randomized, placebo-controlled studies

BACKGROUND: Anxiety comorbidity is common in patients with bipolar disorder and is associated with higher severity and reduced treatment response. The aim of this study was to assess the efficacy and safety of lurasidone in patients with bipolar depression who present with or without severe anxiety symptoms. METHODS: Data were pooled from 2 bipolar I depression studies of very similar design that randomized patients, double-blind, to 6 weeks of treatment with lurasidone (20-60 mg/day or 80-120 mg/day) versus placebo. Patients were categorized into 2 groups based on their Hamilton Anxiety Rating Scale (HAM-A) score at baseline: a "severe" anxiety group (HAM-A ≥ 18) and a "non-severe" anxiety group (HAM-A < 18). The primary efficacy measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: In the severe anxiety group, significant improvement in the MADRS total score was observed with a moderate effect size (0.40) on lurasidone 20-60 mg, but lurasidone 80-120 mg was not significant (effect size, 0.21); however, in the non-severe anxiety group significant improvement was observed in both lurasidone treatment groups (effect size, 0.51 and 0.54, respectively). Common adverse events were akathisia and nausea, and the change in laboratory parameters and body weight were small and not clinically meaningful. LIMITATIONS: This was a post-hoc analysis of a short-term study. CONCLUSIONS: This analysis suggests that lurasidone 20-60 mg is effective in patients with bipolar I depression regardless of their anxiety severity, with a generally good safety profile.