Background Postpartum depression (PPD) is a significant concern in obstetrics. This study aimed to investigate the effects of hydromorphone in patient-controlled intravenous analgesia (PCIA) on PPD and sleep disorders following cesarean section. Methods A total of 140 parturients undergoing elective cesarean section under combined spinal-epidural anesthesia, with singleton full-term pregnancy and aged 22–35 years, were enrolled from July to December 2025 at Jiangning Hospital Affiliated to Nanjing Medical University. Using a random number table, participants were allocated to two groups based on PCIA formulation: the sufentanil group (Group S) received sufentanil (3 μg/kg) + tropisetron (0.1 mg/kg) diluted to 150 mL with normal saline; the hydromorphone group (Group H) received hydromorphone (0.15 mg/kg) + tropisetron (0.1 mg/kg) diluted to 150 mL with normal saline. The primary outcome was the incidence of PPD at 6 weeks postoperatively. Secondary outcomes included PPD incidence at 1 week, Ramsay sedation scores at 24 and 48 h, Pittsburgh Sleep Quality Index (PSQI) scores preoperatively and at 24/48 h, resting Visual Analog Scale (VAS) pain scores at 6, 12, 24, and 48 h, PCIA button presses and rescue analgesia within 48 h, cumulative 48-hour opioid consumption, bowel function recovery time, first lactation time, neonatal behavioral neurological assessment (NBNA) scores at 48 h postoperatively and adverse reactions. Results The incidence of PPD at 6 weeks was significantly lower in Group H compared to Group S 5.8% vs. 20.6%, relative risk (RR) = 0.28, 95% confidence interval (CI) 0.10 to 0.78, P = 0.004. The absolute risk reduction was 14.8% (95% CI 4.2%–25.4%), corresponding to a number needed to treat (NNT) of 7 (95% CI 4–24). Ramsay and PSQI scores at 24 and 48 h were also significantly lower in Group H ( P 0.01 for all), as was the incidence of dizziness and drowsiness within 48 h ( P 0.01). No significant intergroup differences were found in analgesia-related outcomes or other adverse reactions. Conclusion Hydromorphone for PCIA after cesarean section can reduce the incidence of PPD at 6 weeks, improve early postoperative sleep quality, and decrease dizziness and drowsiness. Clinical Trial Registration https://www.chictr.org.cn/bin/home , identifier ChiCTR2500105264.
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