Efficacy and Safety of Low-Dose Brexpiprazole for Acute Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials

Abstract

Purpose: The purpose of this meta-analysis was to compare the efficacy and safety profile of low-dose brexpiprazole (<2 mg/d) compared to placebo and standard-dose brexpiprazole (2-4 mg/d).

Patients and methods: We identified relevant studies pertaining to the specific purpose of our meta-analysis by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO using the search terms "schizophrenia" or "schizophrenic" AND "brexpiprazole" or "REXULTI". We systematically reviewed all randomized controlled trials (RCTs) comparing low-dose brexpiprazole with placebo. Primary efficacy outcomes were the PANSS total score change and response rate. Primary safety outcomes were total treatment discontinuation rate, and total serious adverse events (SAEs). Risk ratios (RR) and standardized mean differences (SMDs) were pooled implementing a random effect model.

Results: Four RCTs (2178 patients) were included for effect assessment of low-dose brexpiprazole treatment on the patients with acute schizophrenia. Low-dose brexpiprazole was not superior to placebo (SMD = -0.11, 95% CI = -0.23, 0.02, P = 0.10, I² = 0%), and significantly inferior to standard-dose brexpiprazole (SMD = 0.15, 95% CI = 0.03, 0.26, P = 0.01, I² = 0%) for PANSS total score change. Low-dose brexpiprazole did not result in significant difference for response rate when compared to placebo and standard-dose brexpiprazole (RR = 1.16, 95% CI = 0.95, 1.41, P = 0.14, I² = 25%; RR = 0.92, 95% CI = 0.76, 1.12, P = 0.40, I² = 38%, respectively). For ratio of total discontinuation, low-dose brexpiprazole did not exhibit significant difference when compared to placebo (RR = 0.95, 95% CI = 0.81, 1.11, P = 0.53, I² = 0%) and standard-dose brexpiprazole group (RR = 1.11, 95% CI = 0.95, 1.29, P = 0.19, I² = 0%). Total SAEs in low-dose brexpiprazole group did not differ significantly from placebo and standard-dose brexpiprazole group (RR = 0.96, 95% CI = 0.52, 1.80, P = 0.90, I² = 0%; RR = 1.29, 95% CI = 0.65, 2.57, P = 0.47, I² = 26%, respectively).

Conclusion: The results indicated that low-dose brexpiprazole may be not superior for improving the efficacy and safety for acute schizophrenia compared to placebo and standard-dose brexpiprazole, and may cause additional risk of increasing body weight. Therefore, using low-dose brexpiprazole in acute schizophrenia patients may be not recommended.

Keywords: RCTs; acute schizophrenia; brexpiprazole; meta-analysis; placebo.