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.
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