Esketamine reduces 3-month postpartum depression incidence from 20.89% to 11.59% in primiparaeTrial shows esketamine reduces postpartum depression risk in new mothers

BACKGROUND: Postpartum depression (PPD) is a common complication after childbirth, especially in primiparae. OBJECTIVES: This trial sought to evaluate whether prophylactic administration of esketamine during the perinatal period could prevent PPD in primiparae without predisposition to prenatal depression. DESIGN: A prospective, double-blind, multicentre, randomised controlled trial. SETTING: Three academic hospitals. PATIENTS: Primiparae scheduled for elective caesarean section with an Edinburgh Postnatal Depression Scale (EPDS) score less than 10. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.