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

• Published in: PloS one Vol. 19; no. 11; p. e0310751
• Main Authors: Hung, Kuo-Chuan, Kao, Chia-Li, Lai, Yi-Chen, Chen, Jen-Yin, Lin, Chien-Hung, Ko, Ching-Chung, Lin, Chien-Ming, Chen, I-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.11.2024; Public Library of Science (PLoS)
• Subjects: Anesthesia; Antidepressants; Bias; Biology and Life Sciences; Depression, Postpartum - prevention & control; Dosage; Dosage and administration; Drug dosages; Female; Humans; Intervention; Ketamine; Ketamine - administration & dosage; Ketamine - therapeutic use; Medicine and Health Sciences; Mental depression; Meta-analysis; People and Places; Perioperative care; Perioperative Care - methods; Pharmacology, Experimental; Physical Sciences; Physiological aspects; Postpartum; Postpartum depression; Prevention; Randomized Controlled Trials as Topic; Reliability; Research and Analysis Methods; Science Policy; Sequential analysis; Social Sciences; Subgroups; Testing; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0310751

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