Esketamine promising in Reducing Postpartum Depression after Cesarean Deliveries, suggests study

Recent randomized clinical trial was conducted to evaluate the efficacy of intraoperative esketamine in reducing postpartum depression (PPD) among women undergoing cesarean delivery. The trial was carried out at The First Affiliated Hospital of Chongqing Medical University in China, from March 2023 to February 2024. The participants included pregnant patients admitted for cesarean delivery, with exclusions for those having intellectual dysfunction or contraindications to esketamine. A total of 308 women were enrolled and randomly assigned to either the esketamine group (154 participants) or the control group receiving saline (154 participants) in a 1:1 ratio, following the intention-to-treat principle.

Intervention Details

The intervention for the esketamine group involved a 20-minute infusion of 0.25 mg/kg esketamine in saline, whereas the control group received saline only. The primary outcome of interest was the incidence of PPD at 6 weeks postpartum, which was measured using the Edinburgh Postnatal Depression Scale (EPDS). A secondary outcome included the incidence of PPD at 1 week postpartum and assessment of pain levels using a numerical rating scale (NRS) postoperatively.

Results Summary

Results indicated a significantly lower incidence of PPD at 6 weeks postpartum in the esketamine group (10.4%) compared to the control group (19.5%), yielding a relative risk (RR) of 0.53 with a 95% confidence interval of 0.30 to 0.93 (P = .02). Conversely, no significant difference was observed at 1 week postpartum, where incidences were 15.6% for the esketamine group and 24.0% for the control group (RR=0.64; P = .06). At 6 weeks postpartum, EPDS scores also reflected this trend, with lower median scores in the esketamine group (5 vs 6; P = .02), indicating less depressive symptom severity. The findings suggested that esketamine may effectively reduce the incidence of PPD among women undergoing cesarean delivery when assessed at a 6-week follow-up, but not at 1 week postpartum. Stratified analyses did not reveal significant advantages of esketamine in reducing PPD across various subgroups, nor did it impact pain scores after surgery. However, there was a noted reduction in the frequency of patient-controlled intravenous analgesia (PCIA) bolus administration among the esketamine group, which may indicate potential benefits for managing postoperative pain.

Adverse Events and Monitoring

Despite the promising results, the trial noted some adverse events associated with esketamine use, including dizziness, trance-like states, and dream-like sensations. While these effects were transient, they highlighted the need for careful monitoring of patients receiving esketamine. The trial also pointed out that a better understanding of the optimal dosing and administration routes for esketamine could help mitigate adverse reactions and enhance its effectiveness.

Conclusion and Future Research

In conclusion, this trial provided evidence for the potential use of esketamine as a preventive measure against PPD in women who have undergone cesarean delivery, though further research is warranted to confirm these findings and explore the broader clinical implications. Large-scale, multicenter studies are necessary to validate these results and enhance understanding of esketamine's role in postpartum mental health care.

Key Points

- A randomized clinical trial involving 308 women undergoing cesarean delivery was conducted to assess the efficacy of intraoperative esketamine on postpartum depression (PPD), with participants divided equally into esketamine and control groups.

- The intervention for the esketamine group included a 20-minute infusion of 0.25 mg/kg esketamine in saline, while the control group received only saline. The primary outcome measured was the incidence of PPD at 6 weeks postpartum, using the Edinburgh Postnatal Depression Scale (EPDS).

- At 6 weeks postpartum, the esketamine group showed a significantly lower incidence of PPD (10.4%) compared to the control group (19.5%), with a relative risk of 0.53 (95% CI: 0.30 to 0.93, P = .02). No significant difference was recorded at 1 week postpartum, with incidences of 15.6% for esketamine and 24.0% for control (RR=0.64; P = .06).

- EPDS scores reflected improved outcomes at 6 weeks, with the esketamine group reporting lower median scores (5 vs 6, P = .02), indicating reduced depressive symptom severity. Stratified analyses showed no significant differences in PPD reduction across demographic subgroups. - Participants in the esketamine group experienced fewer demands for patient-controlled intravenous analgesia (PCIA) boluses post-surgery, suggesting potential benefits in postoperative pain management, although pain scores did not significantly differ between groups.

- Adverse effects such as dizziness and dream-like sensations were recorded with esketamine use, emphasizing the importance of monitoring. The need for further research, including large-scale multicenter studies, was identified to validate the findings and explore optimal dosing and administration for improved safety and efficacy in managing postpartum mental health.

Reference –

Li Ren et al. (2025). Intraoperative Esketamine And Postpartum Depression Among Women With Cesarean Delivery. *JAMA Network Open*, 8. https://doi.org/10.1001/jamanetworkopen.2024.59331.