Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Objective: The efficacy, safety, and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia.

Method: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with schizophrenia experiencing an acute exacerbation were randomly assigned to daily brexpiprazole at a dosage of 0.25, 2, or 4 mg or placebo (1:2:2:2) for 6 weeks. Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score (primary endpoint measure), Clinical Global Impressions Scale (CGI) severity score (key secondary endpoint measure), and other efficacy and tolerability measures.

Results: The baseline overall mean PANSS total score was 95.2, and the CGI severity score was 4.9. Study completion rates were 62.2%, 68.1%, and 67.2% for patients in the 0.25-, 2-, and 4-mg brexpiprazole groups, respectively, versus 59.2% in the placebo group. At week 6, compared with placebo, brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score (treatment differences: -8.72 and -7.64, respectively) and CGI severity score (treatment differences: -0.33 and -0.38). The most common treatment-emergent adverse event for brexpiprazole was akathisia (2 mg: 4.4%; 4 mg: 7.2%; placebo: 2.2%). Weight gain with brexpiprazole was moderate (1.45 and 1.28 kg for 2 and 4 mg, respectively, versus 0.42 kg for placebo at week 6). There were no clinically or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings.

Conclusions: Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation.

Trial registration: ClinicalTrials.gov NCT01396421.