Effect of esketamine on postpartum depression and pain control after caesarean section: A randomized, double-blind, controlled clinical trial

Abstract Background Postpartum depression (PPD) after cesarean delivery is a common complication. Esketamine's effects on PPD in women undergoing cesarean section remain contradictory, despite ketamine's prophylactic effects. This study evaluated the effect of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) to prevent PPD in women undergoing caesarean section. Methods A total of 275 parturients scheduled for caesarean section and subsequent PCIA were recruited from a single centre and randomised to control (sufentanil 2 µg/kg + tropisetron 10 mg) or esketamine (additional esketamine 1.5 mg/kg). The primary outcome was the incidence of PPD, as measured by the Edinburgh postnatal depression scale (EPDS), following surgery. Secondary outcomes were cumulative sufentanil consumption, numerical rating scale (NRS) scores, stress hormone levels and biomarkers of PPD. Results A total of 246 postpartum women with caesarean delivery were included in the final analysis. The incidence of depression among parturients on postoperative day 42 was higher in the control group compared to the esketamine group, with rates of 17.6% and 8.2% respectively (P = 0.02). The EPDS scores were significantly higher in the control group, with a mean score of 9.02 ± 2.21 vs. 6.87 ± 2.14 in the esketamine group (p < 0.0001). Sufentanil consumption was significantly lower in the esketamine group in the 0–24 h (42.5 ± 4.58 µg vs 50.15 ± 5.47 µg, P = 0.04) and 0–48 h (87.40 ± 9.51 µg vs 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Significant differences in movement were observed between the two groups at 24 and 48 hours after cesarean section (3.39 ± 1.57 vs 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs 3.56 ± 0.76, P = 0.02). Furthermore, the plasma level of stress hormone was significantly lower on postoperative day 3 in the esketamine group compared to the control group. The frequency of side effects observed in both groups was comparable. Conclusions Esketamine (1.5 mg/kg) used as a supplement in PCIA significantly decreases the occurrence of PPD in 42 days and reduced cumulative sufentanil consumption in a span of 48 hours post-cesarean operation, without raising the rate of adverse effects. Trial registration: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.