Background:Lurasidone, an azapirone derivative, is a novel second generation antipsychotic with potent bindingaffinity for dopamine D2, serotonin 5-HT2A, 5-HT7,5-HT1A,and noradrenaline alpha2Creceptors. This updatedmeta-analysis of randomized controlled trials (RCTs) examined the short-term efficacy and tolerability of lur-asidone in the treatment of acute schizophrenia.Methods:Double-blinded RCTs reporting on the short-term effects of lurasidone were included. Standardizedmean difference (SMD) with their 95% confidence interval (CI), and number needed to harm (NNH) werecomputed.Results:The meta-analysis had 8 RCTs with 16 active arms that included 2373 patients with acute schizophreniawho were randomized to either lurasidone (20–160 mg/day; n = 1570) or placebo (n = 803) groups. Lurasidonewas superior to placebo with regard to change in total psychopathology [SMD: -0.34, (95%CI: -0.48, -0.20),P < 0.00001], positive symptoms [SMD: -0.47, (95%CI: -0.57, -0.36), P < 0.00001], negative symptoms [SMD:-0.34, (95%CI: -0.45, -0.22), P < 0.00001], and general psychopathology [SMD: -0.36, (95%CI: -0.48, -0.24),P < 0.00001]. Results were consistent for total psychopathology in 11 out of the 13 subgroups. Lurasidoneresulted in higher weight gain [SMD: 0.15, (95% CI: 0.06, 0.24), P = 0.001] and BMI [SMD: 0.17, (95%CI: 0.07,0.28), P = 0.002] than placebo, but the differences were not clinically significant. Lurasidone group had lessfrequent inefficacy (NNH = 14) and discontinuation due to any reason (NNH = 17), but was associated withmore frequent vomiting, akathisia, dystonia, parkinsonism, somnolence, dizziness, sedation, nausea, and weightgain of≥7% of the initial weight (NNH = 11–50).Conclusion:This meta-analysis of 8 short-term studies supported the efficacy and safety of lurasidone in theacute phase of schizophrenia, particularly at the higher dose range of 80 mg/day.