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Effects of esketamine on postoperative pain, anxiety, depression, sleep, and inflammation in pregnancies undergoing cesarean section: A randomized controlled trial.

Yijun Wang, Xiaolu Lin, Xiang Zou, Renqin Zhang, Juanxia Xing, Li Zhang, Jie Shen, Xiaoliang Zhang, Daju Zhou, Junhua Zhang

PLoS One 2026 DOI: 10.1371/journal.pone.0328585 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 98
Population Single-term pregnant women scheduled for elective cesarean section at Chongqing University Fuling Hospital
Interventions Esketamine Sufentanil
Dose 0.5 mg/kg esketamine intravenous bolus + 0.5 mg/kg in patient-controlled intravenous analgesia; control received normal saline + 4 μg/kg sufentanil PCIA
Duration 24 hours postoperative for primary outcome; follow-up through postoperative day 2
Topics Anxiety Depression Esketamine
Key findings Intravenous esketamine significantly reduced postoperative pain, psychological disorders, and inflammation after cesarean section compared to standard sufentanil alone.

Abstract

Postoperative pain is the most notable issue after cesarean section (CS). The contributing factors include hyperalgesia, anxiety, depression, sleep disorders, and inflammation. In this study, we explored the effects of esketamine on pain, hyperalgesia, depression, anxiety, sleep disorders, and inflammation after CS. This randomized, blinded, controlled trial enrolled single-term pregnant women scheduled for elective CS. This trial was a single-center study conducted at Chongqing University Fuling Hospital. A simple randomization method was used. SPSS version 26.0 generated random numbers. The participants were randomly included in the esketamine group (group E: intravenous esketamine 0.5 mg/kg + sufentanil 4 μg/kg followed by patient-controlled intravenous analgesia with esketamine 0.5 mg/kg) or the control group (C: normal saline + sufentanil 4 μg/kg PCIA). The primary outcome was the maximum pain numerical rating scale (NRS) score within 24 h postoperatively. The secondary outcomes included pain NRS scores for moving incision, visceral, and rest incision pain at 0-6 h, 6-12 h and 12-24 h; pressure pain threshold and tolerance at 30 min and 24 h postoperatively; PCIA drug consumption, number of compressions, and dosage of rescue analgesics; time to first PCIA compression; serum C-reactive protein (CRP) at 24 h; incidence of drug-related side effects; and rates of anxiety, depression, and sleep disorders on postoperative day 2. Ninety-eight women were randomly included in group E (n = 50) or C (n = 48). Group E showed significantly lower maximum NRS pain scores within 24 h (5 [4-5] vs. 6 [5-6], P < 0.0001) and relieved rest incision, visceral, and moving incision pain at all time points. The PCIA compression was significantly delayed and CRP levels, as well as the incidence of postoperative depression, anxiety, and sleep disorders, were lower in group E. There were no statistically significant differences in hyperalgesia or side effects between the groups. Intravenous esketamine could effectively reduce postoperative pain, psychological disorders, and inflammation after CS. This study was registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300078310.

Comparable studies

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

Study Year Design Participants
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Patients with treatment resistant depression 2020 Randomized controlled trial
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response Patients with treatment-resistant depression 2021 Pooled post hoc analysis of two phase 3, double-blind, active-controlled studies
Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray Patients with treatment-resistant depression 2023 Post hoc analysis of two pooled phase 3 double-blind placebo- and active-controlled trials n = 518
Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant Patients aged 18-64 years with treatment-resistant depression 2023 Phase 3, randomized, double-blind, short-term flexibly dosed study n = 223
The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial. Female patients with thyroid cancer scheduled for surgery under general anesthesia 2025 Randomized controlled trial n = 80

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