Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

Taro Kishi; Kazuto Oya; Yuki Matsui; Ikuo Nomura; Kenji Sakuma; Makoto Okuya; Yuki Matsuda; Kiyoshi Fujita; Toshihiko Funahashi; Reiji Yoshimura; Nakao Iwata

doi:10.2147/NDT.S176676

Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

Neuropsychiatr Dis Treat. 2018 Oct 1:14:2519-2530. doi: 10.2147/NDT.S176676. eCollection 2018.

Authors

Affiliations

¹ Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan, tarok@fujita-hu.ac.jp.
² Department of Psychiatry, Jindai Hospital, Toyota, Aichi 470-0361, Japan.
³ Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo105-8461, Japan.
⁴ Department of Psychiatry, Okehazama hospital, Toyoake, Aichi 470-1168, Japan.
⁵ Department of Psychiatry, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

Abstract

Purpose: The purpose of this study was to compare the efficacy and safety of brexpiprazole 4 mg/day (B4) and 2 mg/day (B2) for treating acute schizophrenia.

Patients and methods: We performed three categorical meta-analyses (B4 vs placebo, B2 vs placebo, and B4 vs B2) of double-blind, randomized placebo-controlled trials (DBRCTs) that reported improvements in the Positive and Negative Syndrome Scale (PANSS) scores, response rate, Clinical Global Impression-Improvement and Severity (CGI-I and CGI-S) scores, discontinuation rate, and incidence of individual adverse events.

Results: We identified three DBRCTs with 1,444 patients. Both B4 and B2 were superior to placebo for PANSS total score (B4: standardized mean difference [SMD] =-0.30, 95% CI =-0.43, -0.17; B2: SMD =-0.30, 95% CI =-0.46, -0.13), PANSS negative score, response rate, CGI-S score, and CGI-I score. B2, but not B4, was superior to placebo for the PANSS positive score. However, there was considerable heterogeneity in the meta-analysis for B4's PANSS positive score, which disappeared after excluding a 2018 Japanese study from the meta-analysis that included more patients on a high-dose antipsychotic prior to their participation. A meta-analysis that excluded the data from the abovementioned patients showed B4 to be superior to the placebo in terms of the PANSS positive score (SMD =-0.22, 95% CI =-0.40, -0.03). B2, but not B4, was associated with a lower incidence of all-cause discontinuation compared with placebo. Both B4 and B2 were superior to placebo for discontinuation due to adverse events and schizophrenia, but both were associated with a higher incidence of weight gain compared with placebo. B4 was also associated with a higher risk of extrapyramidal symptoms than B2.

Conclusion: Both B4 and B2 benefitted patients with schizophrenia, particularly those who were not previously on high-dose antipsychotics. Both the regimens were well-tolerated, but carried a risk of weight gain and extrapyramidal symptoms, although the latter risk was higher for B4 than B2.

Keywords: Positive and Negative Syndrome Scale score; brexpiprazole 2 mg/day; brexpiprazole 4 mg/day; meta-analysis; response rate; safety outcomes; schizophrenia; systematic review.