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

Jie Yang, Qiqi Yan, Ting Zhang, Yaoyue Hu, Fangliang Peng, Ruihan Zhao, Meiling Deng, Li Ren

Drug Design, Development and Therapy 2026 DOI: 10.2147/dddt.s601347 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 503
Population Women without prenatal depression undergoing caesarean delivery
Interventions Esketamine Bolus injection Continuous infusion Normal saline
Dose 0.25 mg/kg
Duration 6-week follow-up
Measures Edinburgh Postnatal Depression Scale (EPDS)
Topics Esketamine Depression
Keywords Administration route Caesarean section Postpartum depression
Key findings Esketamine bolus administration and continuous infusion showed comparable efficacy for preventing postpartum depression at six weeks, but bolus administration caused fewer adverse events.

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.

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