Prophylactic esketamine for postpartum depression after cesarean section: a systematic review and meta-analysis

Purpose: According to recent research, esketamine may reduce the incidence of postpartum depression (PPD) risk following cesarean delivery. To further assess this potential benefit, a meta-analysis was conducted. Methods: Embase, Web of Science, the Cochrane Library, and PubMed were searched from inception through March 2025. Meta-analysis was performed using random-effects models to calculate risk ratios (RRs) and mean differences along with their corresponding 95 % confidence intervals (CIs). The primary outcome was the incidence of PPD risk as measured by the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes were EPDS score, Numeric Rating Scale (NRS) postoperative pain score, and the incidence of adverse events. Results: Thirteen studies with 2716 patients were analyzed. Esketamine used perioperatively lowers the risk of PPD and EPDS scores at 1 and 6 weeks after cesarean section and reduces NRS pain scores within 48 h during movement and 24 h at rest. However, it also increases adverse effects like hallucinations, dizziness, blurred vision, and diplopia. Additionally, prenatal body mass index (BMI) is inversely correlated with mood response to esketamine one week after surgery. Limitations: There was clinical heterogeneity, diagnostic interview for PPD with different EPDS score, and sample was not racially diverse among studies. Conclusion: Current research suggests that esketamine may reduce the incidence of PPD risk, EPDS score, and NRS pain score after cesarean section with short-term complications. Prenatal BMI was a negative predictor of the antidepressant efficacy of esketamine.