Bolus versus Continuous Infusion of Esketamine for Prevention of Postpartum Depression After Caesarean Delivery: A Randomized, Double-Blind, Controlled Trial.

Summary

Among women without prenatal depression who delivered by caesarean section, a single bolus injection of 0.25 mg/kg esketamine reduced the rate of postpartum depression (PPD) at six weeks to 9.15%, compared with 19.33% in the saline placebo group. Continuous infusion of the same dose produced a PPD rate of 11.54%, which did not differ statistically from the bolus group. Pain scores were similar across all three groups. The bolus route caused fewer intraoperative adverse events—45.75% versus 65.38% with infusion—especially less dizziness and nausea or vomiting. For preventing PPD, bolus and continuous infusion appear equally effective, but bolus administration may be preferable because it is better tolerated.

Study at a glance

Abstract

Esketamine is increasingly being applied for preventing postpartum depression (PPD). However, clinical protocols for this application are inconsistent, particularly concerning the route of administration. The aim was to determine whether esketamine bolus administration differed from continuous infusion in terms of preventing PPD. A total of 503 subjects without prenatal depression undergoing caesarean delivery were included in this superiority trial and randomly allocated to three groups: the esketamine bolus group received a bolus injection of 0.25 mg/kg esketamine, the esketamine infusion group was administered a continuous infusion of 0.25 mg/kg esketamine, while the control group was given an equivalent volume of normal saline. Primary outcome was set as the incidence of PPD at 6 weeks postpartum. The positive screening of PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) with scores of more than 10. Incidence of PPD at 1 and 4 weeks postpartum, pain scores and all adverse events were also assessed. Esketamine bolus administration significantly reduced the incidence of PPD compared with control group (9.15% vs 19.33%; RR 0.47, 95% CI 0.25-0.91). However, no statistically significant difference was observed between the bolus group and the infusion group (9.15% vs 11.54%; RR 0.79, 95% CI 0.40-1.57). There were no significant differences in PPD incidence at 1 and 4 weeks postpartum among the three groups. Similarly, the analgesic effects were comparable across the three groups. Regarding adverse events, less dizziness and nausea/vomiting during surgery was revealed with esketamine bolus administration. Overall, subjects receiving esketamine bolus administration also experienced fewer intraoperative adverse events than those in the infusion group (45.75% vs 65.38%, RR 0.73, 95% CI 0.56-0.95). For patients without prenatal depression undergoing caesarean delivery, esketamine bolus administration or continuous infusion demonstrated comparable efficacy for preventing PPD, bolus administration may be the preferred route due to a lower incidence of adverse events.