Objective  To systematically evaluate the efficacy and safety of Esketamine on postpartum depression (PPD) in cesarean section women.

Methods  Databases including PubMed, Embase, Web of Science, The Cochrane Library, CBM, CNKI, WanFang and VIP were searched from inception to March 2025 for RCTs investigating the impact of Esketamine on PPD in cesarean section parturients. RevMan 5.4 and Stata 18.0 software was used for Meta-analysis.

Results  A total of 15 RCTs involving 2,801 patients were included, with 1,516 in the Esketamine group and 1,285 in the control group. The Meta analysis showed that the incidence of PPD in the Esketamine group at 1 week postoperatively [RR=0.46, 95%CI (0.37, 0.57)] and at 6 weeks postoperatively [RR=0.63, 95%CI (0.51, 0.78)] was significantly lower than that in the control group. Futhermore, the EPDS scores were also significantly lower in the Esketamine group within 1 week postoperatively [MD=−2.52, 95%CI (−3.53, −1.50)] and at 6 weeks post-operatively [MD=−2.60, 95%CI (−4.09, −1.10)] was significantly lower than those in the control group. However, the incidence of intraoperative dizziness [RR=10.10, 95%CI (5.42, 18.84)] and hallucinations  [RR=8.70, 95%CI (3.11, 24.34)] was significantly higher in the Esketamine group. There was no statistically significant difference in the incidence of postoperative nausea and vomiting [RR=0.87, 95%CI (0.62, 1.24)] and dizziness [RR=1.48, 95%CI (0.93, 2.34)] between the two groups.

Conclusion  Perioperative use of Esketamine reduces the incidence of PPD after cesarean section but is associated with transient neuropsychiatric symptoms during surgery, without increasing postoperative adverse reactions.

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