Prophylactic esketamine to reduce postpartum depression in primiparae: A multicentre, double-blind, randomised clinical trial.

A single dose of esketamine given intravenously around the time of cesarean section, followed by 24 hours of low-dose esketamine in patient-controlled pain relief, reduced the overall incidence of postpartum depression within three months after childbirth in first-time mothers who were not already depressed. The total rate of postpartum depression was 11.59% in the esketamine group versus 20.89% in the saline control group. The benefit was most evident at 7 days postpartum, with no significant differences at 1, 2, or 3 months individually. Mild side effects like dizziness, hallucination, and dissociation occurred in some women. The treatment appears relatively safe and prevents postpartum depression in the short term.

Study at a glance

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.