Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan

Neuropsychopharmacol Rep. 2020 Sep;40(3):314-322. doi: 10.1002/npr2.12131. Epub 2020 Aug 7.

Abstract

Introduction: Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random-effect model network meta-analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.

Methods: The study included the double-blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS-T, primary), positive (PANSS-P), negative (PANSS-N), and general (PANSS-G) subscale scores; and Clinical Global Impression-Severity Scale (CGI-S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.

Results: We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS-T [standardized mean difference (95% credible interval): LUR40 = -0.298 (-0.420, -0.176), LUR80 = -0.170 (-0.320, -0.019)], PANSS-P, and CGI-S scores, LUR40 but not LUR80 outperformed placebo in PANSS-N and PANSS-G scores and response rate. LUR40 outperformed LUR80 regarding PANSS-G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug-Induced Extrapyramidal Symptoms Scale score.

Conclusions: Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.

Keywords: Japan clinical trial; acute schizophrenia; efficacy/safety/tolerability; systematic review and network meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Clinical Trials, Phase III as Topic / methods*
  • Double-Blind Method
  • Humans
  • Japan / epidemiology
  • Lurasidone Hydrochloride / therapeutic use*
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic / methods*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Lurasidone Hydrochloride