Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: A double‐blind, randomized clinical trial

BACKGROUND: Postpartum depression (PPD) is a common mental disease happens in perinatal period. Ketamine as an anesthesia and analgesia drug has been used for a long time. In recent years, ketamine is proved to have an antidepression effect with a single administration. We hypothesized that intraoperative ketamine can reduce postpartum depressive symptoms after cesarean delivery. METHODS: In a randomized, double‐blind, placebo‐controlled study trail, healthy women scheduled for cesarean delivery were randomly assigned to receive intravenous ketamine (0.25 mg/kg diluted to 5 ml with 0.9% saline) or placebo (5 ml of 0.9% saline) within 5 min following clamping of the neonatal umbilical cord. The primary outcome was the degree of postpartum depressive symptoms, which was evaluated by Edinburgh Postnatal Depression Scale (EPDS, a threshold of 9/10 was used) at 1 week, 2 weeks, and 1 month after delivery. The secondary outcome was the numerical rating scale (NRS) score of pain at 2 days postpartum. This trail is registered in the Chinese Clinical Trial Registry, number ChiCTR1900022464. RESULTS: Between 26 January 2019 and 15 July 2019, 502 subjects were screened and 330 were randomly allocated: 165 (50%) to the ketamine group and 165 (50%) to the placebo group. There were significant differences in the degree of postpartum depressive symptoms between subjects in the ketamine group and the placebo group at 1 week postpartum (13.1% vs. 22.6%, respectively; p = .029). However, no difference was found between subjects in the two groups at 2 weeks (11.8% vs. 16.8%, respectively; p = .209) and 1 month postpartum (10.5% vs. 14.2%, respectively; p = .319). The NRS score of wound pain (3.0 ± 0.9 vs. 4.0 ± 1.0, respectively; p < .001) and uterine contraction pain (3.0 ± 0.9 vs. 4.1 ± 0.9, respectively; p < .001) was lower in the ketamine group at 2 days postpartum compared with placebo group. The prevalence of headache, hallucination, and dizziness was higher in the ketamine group than the placebo group during the operation. CONCLUSIONS: Operative intravenous ketamine (0.25 mg/kg) can reduce the postpartum depressive symptoms for 1 week. The long‐time effect is remained to be seen.