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Efficacy of esketamine after cesarean section for women with symptoms of prenatal depression: A randomized controlled trial.

Xue-Song, Ying-Yan Xu, Hua-Ping Xiong, Li-Tang, Qing-Ren Liu, Deng-Xin Zhang

Psychiatry Research November 16, 2025 DOI: 10.1016/j.psychres.2025.116849 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 174
Population Pregnant women with Edinburgh Postnatal Depression Scale scores ≥ 10 undergoing cesarean section
Intervention Esketamine
Dose 0.25 mg/kg after umbilical cord clamping plus 1.25 mg/kg in postoperative patient-controlled intravenous analgesia
Duration 6 weeks postpartum follow-up
Topics Esketamine Depression
Keywords Cesarean section High-risk population Postpartum depression prevention
Citations 2
Key findings Perioperative esketamine reduced postpartum depression incidence at 6 weeks postpartum from 39.3% to 18.8% (odds ratio 0.36).

Abstract

Postpartum depression (PPD) is a major global health issue. Although esketamine shows promise for PPD, its preventive effect in cesarean patients with prenatal depression remains unclear. The aim of this trial was to evaluate the effect of perioperative esketamine treatment on PPD incidence in this high-risk population. This dual-center, double-blind, randomized, placebo-controlled trial enrolled 174 pregnant women with Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 10 undergoing cesarean section. Participants were randomized 1:1 to esketamine or control groups. After umbilical cord clamping, the esketamine group received 0.25 mg/kg esketamine, the control group normal saline placebo. Postoperative patient-controlled intravenous analgesia (PCIA) included 100 μg sufentanil in both groups, with 1.25 mg/kg esketamine added in the esketamine group. The primary outcome was PPD incidence (EPDS≥10) at 6 weeks postpartum. Secondary outcomes included the prevalence of postpartum anxiety (PPA) risk, postoperative pain, opioid consumption, postoperative sleep duration and adverse events. PPD occurred in 18.8 % of participants (n = 85) in the esketamine group and 39.3 % (n = 84) in the control group (odds ratio, 0.36 [95 % CI, 0.18-0.72]; P = 0.004). Early benefits were observed at 3 days postoperatively, with reduced PPD and PPA risks. Esketamine provided better early analgesia, with lower pain scores and reduced sufentanil use within 48 h postoperatively. Longer sleep duration was reported in the esketamine group. Dizziness incidence was higher with esketamine both intraoperatively and postoperatively. Perioperative esketamine reduces PPD incidence in women with prenatal depression, with added benefits on early anxiety, pain, opioid use, and sleep. Dizziness was the only notable side effect.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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