Efficacy and safety of zuranolone in major depressive disorder: a meta-analysis of factor effect and dose-response analyses

Yu-Wei Lin; Yu-Kang Tu; Kuo-Chuan Hung; Chih-Sung Liang; Ping-Tao Tseng; Pao-Yen Lin; Edward Chia-Cheng Lai; Chih-Wei Hsu

doi:10.1016/j.eclinm.2023.102308

Efficacy and safety of zuranolone in major depressive disorder: a meta-analysis of factor effect and dose-response analyses

EClinicalMedicine. 2023 Nov 16:66:102308. doi: 10.1016/j.eclinm.2023.102308. eCollection 2023 Dec.

Authors

Yu-Wei Lin¹, Yu-Kang Tu^{2

3}, Kuo-Chuan Hung⁴, Chih-Sung Liang^{5

6}, Ping-Tao Tseng^{7

8

9

10}, Pao-Yen Lin¹, Edward Chia-Cheng Lai¹¹, Chih-Wei Hsu¹

Affiliations

¹ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
² Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
³ Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.
⁵ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan.
⁷ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan.
⁸ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
¹⁰ Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
¹¹ School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Abstract

Background: Zuranolone is recognised as a promising antidepressant agent. Our study aimed to investigate the efficacy and safety of zuranolone in treating major depressive disorder (MDD).

Methods: A systematic review was conducted by searching major databases from inception to August 20, 2023 (INPLASY: 202360087). A meta-analysis was performed by using a random-effects model to calculate effect sizes, expressed as standardised mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was improvement in depressive symptoms, while secondary outcomes included response and remission rates of depression, improvement in anxiety symptoms, incidence of dropouts, and any side effects. We conducted subgroup analyses for general MDD and postpartum-onset MDD and a dose-response meta-analysis to estimate the relationship between zuranolone dose and outcomes.

Findings: The study included seven randomised control trials involving 1789 patients. Zuranolone reduced depressive symptoms (SMD = -0.37, 95% CIs = -0.51 to -0.23), increased response rate (OR = 2.06, 95% CIs = 1.48-2.85) and remission rate (OR = 2.04, 95% CIs = 1.38-3.02), and reduced anxiety symptoms (SMD = -0.26, 95% CIs = -0.39 to -0.14). Furthermore, zuranolone-treated patients experienced more side effects than those in the control group (OR = 1.40, 95% CIs = 1.10-1.78), although dropout rate did not significantly differ between the two groups (OR = 1.13, 95% CIs = 0.85-1.49). According to the dose-response meta-analysis, zuranolone could effectively improve depression and anxiety at increasing doses up to a maximum daily dose of 30 mg; however, side effects increased with doses exceeding 30 mg. Based on subgroup analyses, zuranolone showed greater efficacy in treatment of postpartum-onset MDD than general MDD, but the difference did not reach statistical significance.

Interpretation: Our findings suggested that zuranolone is effective in alleviating depression and anxiety. Nevertheless, there is a potential risk of adverse effects. Given its therapeutic efficacy and risk of side effects, a daily dose of 30 mg appears to be the optimal choice.

Funding: Chang Gung Medical Foundation.

Keywords: DRMA; Depression; MDD; Postpartum; SAGE-217; Zuranolone.