Meta-analysis of Six RCTs Shows Modest Reduction in Early Postpartum Depressive Symptoms With Perioperative Ketamine After Cesarean

The meta-analysis pooled data from RCTs published 2015-2025 that tested ketamine or esketamine given during or immediately after elective C-section versus placebo or standard care. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale on postoperative days 3-14. The pooled effect was statistically significant yet small-to-moderate in magnitude, consistent with ketamine's known rapid antidepressant properties in other settings but applied here to a surgical obstetric population already at elevated risk for mood disturbance.

C-sections are linked to higher postpartum depression rates than vaginal births, possibly through inflammatory, pain-related, and recovery stressors. The observed benefit aligns with emerging data on sub-anesthetic ketamine for treatment-resistant depression, yet the analysis captured only early symptom scores rather than clinician-diagnosed major depression or functional outcomes. Funding sources for included trials were not detailed in the meeting presentation, leaving potential industry influence unexamined.

Larger prospective trials with longer follow-up are required to test whether symptom reduction translates into lower incidence of postpartum depression at six to twelve weeks and to define optimal dosing. The planned University at Buffalo RCT will address incidence and severity endpoints directly.

Evidence quality remains moderate: six RCTs provide randomization but the analysis is preliminary, conference-reported, and limited to short-term surrogate screening scores without clinical diagnosis or maternal-infant outcome data.