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

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.