Effects of different doses of esketamine intervention on postpartum depressive symptoms in cesarean section women: A randomized, double-blind, controlled clinical study

Abstract

Background: The optimal dosage and method of esketamine for postpartum depressive symptoms (PDS) are unclear. We conducted a randomized controlled trial (RCT) to investigate the effect of different doses of esketamine on PDS in women undergoing cesarean section, with evidence of prenatal depression.

Methods: The three groups were high- (2 mg kg^-1) and low-dose (1 mg kg^-1) esketamine via patient controlled intravenous analgesia (PCIA), following an initial intravenous infusion of 0.25 mg kg^-1 esketamine, compared to placebo (0.9 % saline infusion). All groups also received the sufentanil (2.2 μg kg^-1). The primary outcome was the incidence of PDS at 7 and 42 days postpartum. The secondary outcomes were: the remission from depression and total EPDS scores at 7 days and 42 days postpartum; mean change from baseline in the EPDS score; postoperative analgesia.

Results: i). 0.25 mg kg^-1 of esketamine intravenous infusion combined with 1 mg kg^-1 (n = 99) or 2 mg kg^-1 (n = 99) esketamine PCIA reduces PDS incidence at 7 days postpartum (p < 0.05), with high-dose esketamine PCIA also reduces PDS incidence 42 days postpartum (p < 0.05), compared to placebo (n = 97). ii). Low- and high-dose esketamine PCIA lowers NRS scores at rest within 48 h postoperatively (p < 0.01), with high-dose esketamine also reducing the NRS score during movement at 48 h postoperatively (p = 0.018). iii). Neither high- nor low-dose esketamine PCIA increased postoperative adverse reactions (p > 0.05).

Conclusions: Esketamine (0.25 mg kg^-1) intravenous infusion combined with 1 mg kg^-1 or 2 mg kg^-1 esketamine PCIA seems safe and with few adverse effects in the management of PDS and pain in women undergoing cesarean section.

Limitations: The tolerability and safety of esketamine requires further investigation based on more specific scales; the transient side effects of esketamine could have biased the staff and patients.

Trial registration: ChiCTR-ROC-2000039069.

Keywords: Esketamine; Postpartum depression; Postpartum depressive symptoms; Prenatal depression; Prophylactic interventions.