Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

Kuo-Chuan Hung; Chia-Li Kao; Yi-Chen Lai; Jen-Yin Chen; Chien-Hung Lin; Ching-Chung Ko; Chien-Ming Lin; I-Wen Chen

doi:10.1371/journal.pone.0310751

Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

PLoS One. 2024 Nov 18;19(11):e0310751. doi: 10.1371/journal.pone.0310751. eCollection 2024.

Authors

Kuo-Chuan Hung¹, Chia-Li Kao², Yi-Chen Lai¹, Jen-Yin Chen^{1

3}, Chien-Hung Lin¹, Ching-Chung Ko^{4

5}, Chien-Ming Lin¹, I-Wen Chen¹

Affiliations

¹ Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.
² Department of Anesthesiology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
³ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁴ Department of Medical Imaging, Chi Mei Medical Center, Tainan City, Taiwan.
⁵ Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan City, Taiwan.

Abstract

Objective: Postpartum depression (PPD) is a major mental health issue affecting 10%-15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine's efficacy in preventing PPD.

Methods: Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4-6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability.

Results: A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3-0.57) and 4-6-week (RR, 0.47; 95%CI, 0.35-0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], -0.94; 95%CI, -1.26 to -0.62) and 4-6-week (SMD, -0.89; 95%CI, -1.25 to -0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence's reliability. Subgroup analysis showed that ketamine/esketamine's preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4-6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39-16.44) and dizziness (RR, 1.36; 95%CI, 1.02-1.81).

Conclusion: Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation.

Copyright: © 2024 Hung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Meta-Analysis

MeSH terms

Depression, Postpartum* / prevention & control
Female
Humans
Ketamine* / administration & dosage
Ketamine* / therapeutic use
Perioperative Care / methods
Randomized Controlled Trials as Topic

Substances

Ketamine
Esketamine

Grants and funding

This research was funded by Chi Mei Medical Center, Tainan, Taiwan, grant number CMOR11102. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.