Double‐blind, placebo‐controlled study of lurasidone monotherapy for the treatment of bipolar I depression

Abstract

Aim: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan. Methods: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Results: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (−13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (−12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (−10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control. Conclusion: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

Lurasidone in the long-term treatment of Japanese patients with bipolar I disorder: a 52 week open label study

“…Overall, the results of the current study suggest that 52 weeks of treatment with lurasidone, in doses up to 120 mg/day, has a relatively low potential for causing adverse weight and metabolic effects. As such, the current study extends the safety findings of previous studies of lurasidone (Loebel et al 2014a;Kato et al 2020;Ketter et al 2016) for bipolar depression to a Japanese population and to bipolar patients with a most recent manic, hypomanic, or mixed episode. Importantly, the current safety findings also extend the shorter-term findings of previous studies of lurasidone for bipolar disorder to a full year of safety monitoring.…”

“…The higher rate of akathisia observed in the current study appears to be attributable to the fact that the placebo-treated subgroup of depressed patients, that entered the current study after completing the Kato et al study (2020) was switched to an initial dose of 60 mg of lurasidone with no titration. In contrast, patients in the previous short-term studies (Loebel et al 2014a;Kato et al 2020) were treated initially with a 20 mg dose for 7 days prior to gradual titration up to their assigned fixed dosage group. Over the course of 52 weeks of lurasidone treatment, there were no meaningful mean changes (largely decreases) in total cholesterol, LDL cholesterol, blood glucose, haemoglobin A1C, or prolactin.…”

“…The study population consisted of two groups of Japanese patients. In the first group were Japanese patients who had completed an initial 6 week, double-blind, placebocontrolled, evaluation (Kato et al 2020) of lurasidone in the treatment of bipolar depression and enrolled in a subsequent 52 week open-label extension phase. This group is labeled the "depressed episode" sample here.…”

“…The atypical antipsychotic drug lurasidone has high affinity for D2, 5-HT7 and 5-HT2A receptors (antagonist), moderate affinity for 5-HT1A receptor (partial agonist), and no appreciable affinity for H1 and M1 receptors (Ishibashi et al 2010). The efficacy of lurasidone as a monotherapy and as an adjunctive therapy with lithium or VPA has been established for the acute treatment of bipolar depression (Loebel et al 2014a, b;Kato et al 2020). Two longer terms studies of lurasidone for bipolar depression have been conducted.…”

“…Despite the three short-term positive trials of lurasidone as a monotherapy or adjunctive therapy for bipolar depression (Loebel et al 2014a, b;Kato et al 2020), and the two extension trials of 24 and 28 weeks (Ketter et al 2016;Ishigooka et al 2021), the generalizability of the results to a Japanese population and to bipolar patients with a most recent manic, hypomanic, or mixed episode is uncertain. In addition, safety and symptom changes over the course of longer term (beyond 28 weeks) lurasidone treatment for bipolar disorder has not been reported.…”