Prophylactic esketamine to reduce postpartum depression in primiparae: A multicentre, double-blind, randomised clinical trial.
European journal of anaesthesiology – January 29, 2026
Source: PubMed
Summary
Prophylactic esketamine significantly reduced postpartum depression (PPD) in new mothers undergoing elective C-sections. Among 322 primiparae, PPD incidence within three months was 11.59% with esketamine versus 20.89% without. Notably, by 7 days, only 4.89% of treated mothers developed PPD, compared to 15.19% in the control group—a 68% reduction. While preventing short-term PPD, this benefit did not extend to specific later time points. Mild side effects like dizziness (10.98%) occurred.
Abstract
Postpartum depression (PPD) is a common complication after childbirth, especially in primiparae. This trial sought to evaluate whether prophylactic administration of esketamine during the perinatal period could prevent PPD in primiparae without predisposition to prenatal depression. A prospective, double-blind, multicentre, randomised controlled trial. Three academic hospitals. Primiparae scheduled for elective caesarean section with an Edinburgh Postnatal Depression Scale (EPDS) score less than 10. Postnatal women were randomly assigned to receive either i.v. esketamine in a single dose of 0.25 mg kg-1 followed by 80 mg of esketamine as an adjunct to 24-h patient-controlled intravenous analgesia (PCIA). Women in the control group received an equal volume of saline. The primary outcome was the total incidence of PPD within 3 months postpartum. Secondary outcomes included postoperative EPDS scores, numeric rating scale scores, sufentanil consumption, the number of effective presses for postoperative intravenous analgesia and adverse events. A total of 322 patients were included in the modified intention-to-treat analysis. The total incidence of PPD in the esketamine group (11.59%) was significantly less than the control group (20.89%) [adjusted relative ratio (RR), 0.57; 95% CI, 0.35 to 0.94; P = 0.028] as was the incidence at 7 days postpartum (4.89 vs. 15.19%; adjusted RR, 0.32; 95% CI, 0.15 to 0.72; P = 0.005). However, there were no significant differences in PPD incidence and EPDS scores at 1, 2 and 3 months postpartum, respectively. Several mild central nervous events, such as dizziness (10.98%), hallucination (10.37%) and dissociation (5.49%), were observed during esketamine treatment. Peri-operative adjunctive administration of esketamine is relatively safe and can prevent PPD in primi-parae without predisposition to prenatal depression in the short term. Trial registration: Clinicaltrials.gov. Identifier: NCT04860661.