The effect of ketamine on preventing postpartum depression

Postpartum depression is described as a common and disabling condition with reported prevalence estimates of 10% to 15% globally and higher reported rates in Iran (25% to 42.1%). The paper emphasises the broad negative consequences of postpartum depression for mothers, infants and families, including impairments in mother–infant interaction, reduced neonatal care, and economic costs, and notes that many affected women do not seek or continue standard pharmacological treatment during breastfeeding. Alipoor and colleagues set out to evaluate whether administering a single low dose of intravenous ketamine during induction of general anaesthesia for elective caesarean section could prevent postpartum depression. The study addresses a gap in the literature: while ketamine’s rapid antidepressant effects are well described in treatment-resistant major depression, its prophylactic potential for postpartum depression during caesarean section has been little studied.

This was a double-blind, randomised clinical trial conducted at teaching centres affiliated with Rafsanjan University of Medical Sciences. Eligible participants were pregnant women aged 18–35 years scheduled for elective caesarean section, ASA class 1 or 2, with low-risk pregnancies and no history of relevant underlying disease or drug abuse; post-delivery haemorrhage requiring transfusion and withdrawal of consent were exclusion criteria. The extracted text reports a sample size calculation that originally envisaged about 35 participants per group, but the final analysed sample comprised 67 participants in each arm; the extract does not clearly explain this discrepancy. After providing written informed consent, participants completed a demographic questionnaire and the Edinburgh Postnatal Depression Scale (EPDS) at baseline (pre‑caesarean). Simple randomisation allocated women to one of two groups. In the intervention arm, induction comprised Nesdonal (reported 1–2 mg/kg) plus ketamine 0.5 mg/kg intravenously; the control arm received Nesdonal only (reported 3–5 mg/kg). Follow-up EPDS assessments were conducted at two and four weeks postoperatively by telephone. Outcome measurement focused on depressive symptoms as measured by the 10‑item EPDS (score range 0–30; scores ≥13 indicate possible depression warranting further assessment). Data were analysed using repeated‑measures analysis of variance and Chi‑square tests in SPSS v18. The study received ethical approval from the university ethics committee and was registered in the Iran Clinical Trial Registration Center; the extract indicates the investigators obtained ethics approval and trial registration numbers.

A total of 134 participants were analysed, with 67 in the ketamine–Nesdonal group and 67 in the Nesdonal alone group. Mean maternal age did not differ significantly between groups (ketamine 28.24±4.81 years; control 27.4±4.09 years). The groups were reported as similar at baseline for parity, pregnancy intention, education, prior depression history and life satisfaction. Baseline EPDS scores were virtually identical between groups (intervention 13.78±3.87, control 13.79±4.78; reported p = 0.98). At two weeks post‑caesarean the mean EPDS was 11.82±3.41 in the ketamine group versus 14.34±4.29 in the control group (reported p < 0.001). At four weeks the means were 10.84±3.48 and 13.09±3.79, respectively (reported p = 0.001). The authors therefore report that EPDS scores declined over time in the ketamine group and were significantly lower than in controls at both follow‑ups; the ketamine group’s scores fell below the EPDS threshold of 13 at two and four weeks. Apgar scores were also reported: the first‑minute Apgar was 7.82±0.68 in the ketamine group and 7.30±0.63 in the control group; the extracted text describes this difference as statistically significant but reports the p‑value inconsistently (p reported as > 0.001, which is unclear). All neonates had a fifth‑minute Apgar of 10. The investigators treated the first‑minute Apgar as a potential confounder; the interaction between time and Apgar score was non‑significant (P = 0.71, F = 0.35), while the interaction between time and treatment group was significant (P < 0.001, F = 14.17). Within‑group analyses reported by the paper indicate a significant decrease in EPDS over time in the ketamine arm; in the control arm EPDS increased at two weeks (not statistically significant) and fell by four weeks (statistically significant compared with two weeks) but remained above the EPDS cut‑off of 13.

Alipoor and colleagues interpret their findings as evidence that a single intravenous dose of ketamine given during induction of anaesthesia for elective caesarean section reduced depressive symptom scores at two and four weeks postpartum compared with control anaesthesia. They note that the ketamine group’s EPDS scores fell below the threshold indicating possible depression, whereas the control group’s scores remained at or above that threshold at follow‑up. The discussion situates these results within prior literature: some clinical studies (cited by the authors) found a preventative or therapeutic effect of perioperative ketamine on postpartum depression, while others did not. The investigators suggest that differences in ketamine dose may explain discrepant findings across studies, and they reference animal work in which ketamine produced more rapid and stable improvements than fluoxetine. The authors also highlight ketamine’s established roles in obstetric analgesia and labour analgesia, noting prior studies that reported favourable analgesic effects and no adverse impact on neonatal Apgar scores. The paper acknowledges uncertainty and the need for further research: despite reporting a significant group-by-time interaction, the authors call for larger clinical trials to confirm ketamine’s prophylactic effect on postpartum depression and to establish safety and appropriate dosing. They state that the minor difference in first‑minute Apgar scores was not clinically important and, after adjustment, did not account for the observed effect on depressive symptoms. The authors propose that, if confirmed, ketamine could become a multipurpose and affordable option in obstetric care for women at higher risk of postpartum depression.

The authors conclude that a single intravenous dose of ketamine administered during induction of anaesthesia for caesarean section may be effective in preventing postpartum depression. They highlight ketamine’s affordability and availability and suggest it could be considered for women at higher risk of postpartum depression, but they emphasise that extensive clinical trials are required to confirm these findings and to establish safety and optimal use.