Efficacy and safety of ketamine and esketamine in reducing the incidence of postpartum depression: an updated systematic review and meta-analysis.

Background: Postpartum depression (PPD) is categorized by the Disorders-Fifth Edition as depression that begins during pregnancy or within the first month after giving birth. Ketamine and esketamine have shown promising results in the treatment of several depressive disorders, which suggests that they may have a role in the prevention of PPD. This systematic review and meta-analysis aim to update evidence about the efficacy and safety of using ketamine and esketamine to reduce PPD incidence.
Methods: We searched four databases, PubMed, Scopus, Web of Science, and Cochrane, to collect relevant studies. We included studies which investigated the preventive effect of ketamine or esketamine on PPD among women after giving birth through caesarean or vaginal delivery. We extracted PPD occurrence rate, PPD score, pain score and side effects. Finally, a meta-analysis was conducted using RevMan software.
Results: Twenty-one eligible studies were incorporated in the current systematic review and meta-analysis involving 4,389 pregnant women. Esketamine was the intervention in 14 studies, and ketamine was used in 7 studies. In subgroup analysis, both ketamine and esketamine were significantly effective in reducing the incidence of short-term PPD (ketamine: RR = 0.72, 95% CI [0.56, 0.93], P = 0.01; esketamine: RR = 0.43, P < 0.0001). Esketamine only significantly reduced the incidence of long-term PPD (RR = 0.44, P < 0.00001). Low doses and high doses were effective in reducing the incidence of both short-term (high dose: RR = 0.48, P = 0.0005; low dose: RR = 0.46, P = 0.002) and long-term PPD (high dose: RR = 0.54, P < 0.0001; low dose: RR = 0.61, P = 0.009). Regarding the risk of side effects, patients in the Ketamine/esketamine group showed statistically significant higher rates of developing dizziness (P = 0.0007), blurred vision (P = 0.02), vomiting (P = 0.004) and hallucinations (P = 0,002) than women in the control group.
Conclusion: Both ketamine and esketamine are effective in lowering the incidence of short-term PPD. On the other hand, only esketamine is effective in reducing the incidence of long-term PPD. It is recommended to use smaller doses for a more tolerable treatment period since doses less than 0.5 mg are significantly effective. Temporary side effects such as dizziness, blurred vision, vomiting and hallucinations were reported.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)