ORIGINAL RESEARCH article
Front. Med.
Sec. Obstetrics and Gynecology
Effect of low-dose esketamine combined with labor analgesia on postpartum depressive symptoms following spontaneous labor: A randomized controlled trial
Dai Zhou 1
Jianxin Gao 1
Lan Dai 1
Lulu Qin 2
Baiqing Duan 1
Dan Peng 1
Xi Huang 1
Liyunjian He 1
Jingni Zou 1
Qin Zhou 1
1. Changsha Hospital for Maternal and Child Health Care, Changsha, China
2. Hunan Normal University, Changsha, China
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Abstract
Background: Postpartum depression (PPD) poses significant risks to maternal and infant well-being. This study aimed to assess the effect of low-dose epidural esketamine combined with labor analgesia on postpartum depressive symptoms and pain scores in women undergoing spontaneous labor. Methods: A randomized controlled trial was conducted with 299 participants assigned to three groups: Group A (esketamine 0.5 mg/kg + labor analgesia), Group B (labor analgesia alone), and Group C (no analgesia). The primary outcome was the Edinburgh Postnatal Depression Scale (EPDS) score at 42 days postpartum. Secondary outcomes included Visual Analogue Scale (VAS) pain scores and serum hormone levels. Results: Overall, EPDS scores were low across the cohort. At 42 days postpartum, no statistically significant difference in EPDS scores was observed between the esketamine group and the analgesia-only group (Group A: 1.97 ± 1.74 vs. Group B: 2.01 ± 1.68). The mean difference was -0.03 (95% CI: -0.46 to 0.39, P = 0.88). The incidence of screen-positive depression (EPDS ≥ 10) was also comparable among groups (4% vs. 2% vs. 6%). Longitudinally, all groups showed temporal improvements in depressive symptoms and pain scores, which coincided with the physiological decline in estrogen and rise in cortisol levels post-delivery. Conclusions: In this low-risk cohort with low baseline depressive symptoms, the addition of low-dose esketamine to labor analgesia did not result in a significant reduction in EPDS scores at 42 days compared to labor analgesia alone. These findings suggest that the potential benefits of esketamine might be limited in populations with a low risk of PPD, and future studies focusing on high-risk groups are warranted. Trial registration: ChiCTR, ChiCTR2500104037. Registered 10 June 2025 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=247161
Summary
Keywords
Epidural analgesia, Esketamine, Labor analgesia, postpartum depression, Spontaneous labor
Received
10 October 2025
Accepted
10 February 2026
Copyright
© 2026 Zhou, Gao, Dai, Qin, Duan, Peng, Huang, He, Zou and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Dai Zhou; Qin Zhou
Disclaimer
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