Association of multimodal analgesic protocol with postpartum depression incidence and sleep quality in high-risk parturients

Background Postpartum depression (PPD) affects 10–20% of women after childbirth, with incidence reaching 30–50% in high-risk populations. Acute postoperative pain and sleep disturbance represent modifiable risk factors. This study evaluated whether a multimodal analgesic protocol combining dexmedetomidine and esketamine is associated with reduced PPD incidence in high-risk parturients undergoing cesarean delivery. Methods This single-center, retrospective cohort study included 82 high-risk parturients who received intraoperative esketamine (0.25 mg/kg) followed by postoperative dexmedetomidine-esketamine patient-controlled analgesia for 48 h between January 2023 and December 2024. Historical controls ( n = 79) from 2022 received standard sufentanil-based analgesia. The primary outcome was PPD incidence at 6 weeks (Edinburgh Postnatal Depression Scale >10). Results PPD incidence was significantly lower in the intervention group versus controls (14.6% vs. 29.1%; relative risk 0.50, 95% confidence interval 0.27–0.93; p = 0.028; number needed to treat 6.9). Edinburgh Postnatal Depression Scale (EPDS) score decreased more in the intervention group (−2.8 ± 3.4 vs. +0.6 ± 4.1; p < 0.001). Sleep quality at postoperative day 7 was better (Pittsburgh Sleep Quality Index 6.2 ± 2.8 vs. 8.9 ± 3.1; p < 0.001). Opioid consumption decreased by 21.2% ( p < 0.001). Exploratory biomarker assessment in a subset suggested lower interleukin-6 and higher brain-derived neurotrophic factor (both p < 0.001), though these data were non-systematic. Psychotomimetic effects occurred in 8.5%, all transient. No significant differences in cardiovascular or respiratory adverse events were observed. Conclusion A multimodal analgesic protocol incorporating dexmedetomidine-esketamine multimodal analgesic protocol was associated with lower postpartum depression incidence, better sleep quality, and acceptable safety in high-risk parturients. Randomized trials are needed to establish causality.