RESIDENT: Ketamine and Esketamine for Post-partum Depression: A Systematic Review and Network Meta-analysis

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Presenting Author(s): Gilmar Gutierrez

Co-Author(s): Isis Lunsky, Xena Wang, Andrea Zhuang, Jennifer Swainson

Date and time: 21 Mar 2026 from 15:35 to 15:50

Location: Saddleback & Glacier  

Learning Objectives

1. Explore the ketamine and esketamine interventions available in the literature for the management of PPD;
2. Consider the benefits of ketamine and esketamine in the prevention of PPD; and
3. Consider the benefits and potential drawbacks of ketamine and esketamine compared to other available interventions. 

Abstract

Introduction: Post-partum Depression (PPD) is a common condition with potentially serious consequences for both mother and baby if left untreated. Ketamine and Esketamine are rapid acting antidepressants shown effective for the treatment of depression, and have been suggested as potential novel agents that could reduce the risk of PPD. 

Methods: This was a systematic review and network meta-analysis. The systematic search was conducted considering studies on the use of ketamine or esketamine, delivered via any modality, to pregnant or postpartum individuals who underwent either c-section or vaginal deliveries, for prevention or treatment of PPD. The extracted data was analyzed using a network meta-analysis approach to develop a comprehensive understanding of the available interventions in the literature. 

Results: 29 studies were identified, including 28 for prevention of PPD. One study reported promising results using IV esketamine in the treatment of PPD. Four studies included individuals who underwent vaginal delivery, 24 studies included individuals who underwent c-section, and one included both individuals who delivered by c-section or vaginally. Patients receiving ketamine or esketamine during or after delivery had a lower risk of developing PPD and lower postpartum pain with a moderate effect size. 

Conclusions: This review showed that there is a scarcity of evidence for the management of PPD, including studies on the use of ketamine or esketamine interventions. Preliminary evidence suggests promise in the use of these agents for prevention of PPD, however guidelines have argued against these treatments for this patient population. As such, more research is needed. 

Literature References

1. Kaufman Y, Carlini S, Deligiannidis K. Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants. Ther Adv Psychopharmacol [Internet]. 2022 [cited 2025 Jan 14];12. Available from: https://journals.sagepub.com/doi/epub/10.1177/20451253211065859 
2. Hung KC, Kao CL, Lai YC, Chen JY, Lin CH, Ko CC, et al. Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis. PLOS ONE. 2024 Nov 18;19(11):e0310751. 
3.  Gilder ME, Tun NW, Carter A, Tan FFSL, Min AM, Eh H, et al. Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting. BMC Pregnancy Childbirth. 2021 Feb 9;21(1):121. 
4. Leung F, Miljanic S, Fernandes V, Tabbara N, De Castro C, Burry L, et al. Eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials. Arch Womens Ment Health. 2023 Jun 1;26(3):353-9. 
5. Vigod SN, Frey BN, Clark CT, Grigoriadis S, Barker LC, Brown HK, et al. Canadian Network for Mood and Anxiety Treatments 2024 Clinical Practice Guideline for the Management of Perinatal Mood, Anxiety, and Related Disorders: Guide de pratique 2024 du Canadian Network for Mood and Anxiety Treatments pour le traitement des troubles de l'humeur, des troubles anxieux et des troubles connexes périnatals. Can J Psychiatry Rev Can Psychiatr. 2025 Feb 12;7067437241303031.