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Adjunctive Brexpiprazole as a Novel Effective Strategy for Treating Major Depressive Disorder: A Systematic Review and Meta-Analysis

Yoon, Seoyoung MD; Jeon, Sang Won MD; Ko, Young-Hoon MD, PhD; Patkar, Ashwin A. MD; Masand, Prakash S. MD; Pae, Chi-Un MD, PhD; Han, Changsu MD, PhD

Journal of Clinical Psychopharmacology: February 2017 - Volume 37 - Issue 1 - p 46–53
doi: 10.1097/JCP.0000000000000622
Original Contributions

Purpose/Background Brexpiprazole was approved for adjunctive treatment of major depressive disorder (MDD) in 2015. Because only a small number of randomized controlled trials have investigated the use of brexpiprazole in MDD, we performed a meta-analysis.

Methods/Procedures We systematically searched literatures in PubMed, Cochrane Library database, EMBASE, Google Scholar, and up to January 2016. The primary efficacy measure was the mean change in total Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline. Secondary efficacy measures were the mean change in total Hamilton Rating Scale for Depression (17 items) score from baseline and the response (≥50% reduction in MADRS total score) and remission (MADRS total score ≤ 10 with ≥50% reduction) rates.

Findings/Results Four studies fulfilled the inclusion criteria and were included in the analysis. Brexpiprazole showed superior efficacy over placebo with effect sizes (mean differences) of −1.76 (95% confidence interval [CI], −2.45 to −1.07) for MADRS and −1.21 (95% CI, −1.71 to −0.72) for the 17-item Hamilton Rating Scale for Depression. The risk ratios for response and remission were 1.57 (95% CI, 1.29–1.91) and 1.55 (95% CI, 1.22–1.96), respectively. The incidences of discontinuation due to adverse events, akathisia, and weight increase were higher in the brexpiprazole group than in the placebo group, with risk ratios of 3.44 (95% CI, 1.52–7.80), 3.39 (95% CI, 2.08–5.51), and 4.36 (95% CI, 2.45–7.77), respectively, and the incidence of akathisia was related to the brexpiprazole dose.

Implications/Conclusions Although our results suggest that brexpiprazole could be an effective adjunctive agent for MDD, they should be cautiously translated into clinical practice because the meta-analysis was based on only a handful of randomized controlled trials.

From the *Department of Psychiatry, Korea University College of Medicine, Seoul, Korea; †Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC; ‡Academic Medicine Education Institute, Duke-NUS Medical School, Singapore; and §Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Korea.

Received March 2, 2016; accepted after revision October 17, 2016.

Reprints: Changsu Han, MD, PhD, Department of Psychiatry, Korea University College of Medicine, Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Ansan 425-707, Korea (e-mail:

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C003).

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