Perioperative esketamine administration for prevention of postpartum depression after the cesarean section: A systematic review and meta-analysis

Background: Postpartum Depression (PPD) exerts a substantial negative effect on maternal well-being post-delivery, particularly among Cesarean Section (C/S) recipients. In this study, we aimed to review the efficacy of perioperative esketamine, the S-enantiomer of ketamine, in preventing PPD incidence and depressive symptoms as measured with the Edinburgh Postnatal Depression Scale (EPDS) after C/S. Methods: A systematic search for relevant articles was conducted in Scopus, PubMed, Web of Sciences, and PsycINFO until April 6, 2024. Meta-analyses were conducted using random-effect models to compare the PPD incidence and EPDS scores via log odds ratio and Hedge's g, respectively, during the first week post-C/S and at 42 days post-C/S in the esketamine and control group. Results: Fourteen studies, including 12 randomized controlled trials and 2 retrospective cohorts, were reviewed. Our meta-analyses found lower PPD incidence during the first week (log odds ratio: −0.956 [95 % confidence interval: −1.420, −0.491]) and at day 42 post-C/S (log odds ratio: −0.989 [95 % confidence interval: −1.707, −0.272]) among patients administered esketamine compared to controls. Additionally, EPDS scores for the esketamine group were significantly lower than controls during the first week (Hedge's g: −0.682 [95 % confidence interval: −1.088, −0.276]) and at day 42 post-C/S (Hedge's g: −0.614 [95 % confidence interval: −1.098, −0.129]). Limitations: Presence of various concomitant medications and heterogeneous study designs. Conclusion: Our review highlights the potential impact of esketamine in PPD prevention, as well as in alleviating depressive symptoms post-C/S, regardless of PPD occurrence, therefore suggesting the benefits of adding esketamine to peri-C/S analgesic regimen.