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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=247161, identifier ChiCTR2500104037.