Intraoperative Esketamine and Postpartum Depression Among Women With Cesarean Delivery: A Randomized Clinical Trial.

Summary

In a single-center RCT of 308 cesarean deliveries, a single 0.25 mg/kg intraoperative esketamine infusion halved the 6-week postpartum depression incidence versus saline. The effect was assessed by the Edinburgh Postnatal Depression Scale using an intention-to-treat analysis.

Key Findings

• Esketamine reduced 6-week postpartum depression incidence: 10.4% vs 19.5% (RR 0.53; 95% CI 0.30–0.93; P=.02).
• Intervention: single intraoperative infusion 0.25 mg/kg over 20 minutes versus saline control.
• Randomization 1:1, cesarean population, intention-to-treat analysis at a tertiary center.

Clinical Implications

Intraoperative esketamine may be considered for PPD prevention in cesarean deliveries, with attention to safety, dosing, and patient selection. Larger, multicenter trials should confirm efficacy and assess neonatal and breastfeeding outcomes.

Limitations

• Single-center study in China may limit generalizability across diverse health systems.
• Short follow-up (6 weeks) and limited safety/neonatal outcomes reporting.

Future Directions

Multicenter, pragmatic RCTs comparing dosing strategies and timing; evaluation of maternal-infant bonding, breastfeeding, neonatal neurobehavior, and cost-effectiveness.