Effect of Perioperative Ketamine on Early Postpartum Depressive Symptoms Following Cesarean Section: A Meta-Analysis.

A systematic review and meta-analysis of six randomized controlled trials found that perioperative ketamine or esketamine, given during elective cesarean section, significantly reduced early postpartum depressive symptoms measured by the Edinburgh Postnatal Depression Scale between postoperative days 3 and 14. The pooled effect showed a standardized mean difference of -0.36, with moderate heterogeneity. The direction of effect consistently favored ketamine over control. The findings suggest a potential benefit for reducing early postpartum depressive symptom burden, but further research is needed to determine optimal dosing, timing, and long-term clinical impact.

Study at a glance

Abstract

Postpartum depression (PPD) is a common condition associated with adverse maternal and infant outcomes. Higher rates have been observed following cesarean delivery, prompting interest in perioperative preventive strategies. Ketamine has demonstrated rapid antidepressant effects and may provide psychiatric benefits beyond analgesia. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating perioperative ketamine or esketamine for early postpartum depressive symptom reduction in adults undergoing elective cesarean section. PubMed, ScienceDirect, and PsycINFO were searched for studies published between January 2015 and September 2025. Eligible studies reported Edinburgh Postnatal Depression Scale (EPDS) scores between postoperative days 3 and 14. A random-effects model was used to pool standardized mean differences (SMDs), with heterogeneity assessed using the I² statistic. Six randomized controlled trials met the inclusion criteria. Perioperative ketamine or esketamine was associated with a significant reduction in early postpartum depressive symptoms compared with control (SMD = -0.36; 95% CI -0.49 to -0.22). Moderate heterogeneity was observed (I² = 47.5%), with a consistent direction of effect favoring ketamine. These findings suggest that perioperative ketamine may reduce early postpartum depressive symptom burden, though further studies are needed to clarify optimal dosing, timing, and long-term clinical impact.