Ketamine in Prevention and Treatment of Postpartum Depression - Literature Review
DOI:
https://doi.org/10.12775/QS.2025.39.59100Keywords
postpartum depression, ketamine, esketamine, side effects, cesarean section, preventionAbstract
Introduction and purpose: Ketamine, used as an anesthetic and analgesic, has gained considerable attention in recent years in the context of treating various psychiatric disorders, particularly the treatment of drug-resistant depression. A promising application of ketamine appears to be the treatment of postpartum depression. According to the ICD-11 classification, postpartum depression is part of the disorder defined as major depressive disorder and is characterized by the onset of symptoms in the postpartum period, or 12 months after delivery. Conventional treatments for PPD involving both psychotherapy and pharmacotherapy, including non-selective serotonin reuptake inhibitors, may prove inadequate among some patients. ketamine acts on the NMDA receptor and affects the glutamatergic system, showing a significantly rapid antidepressant effect, compared to traditional antidepressants, which may prove crucial in the pharmacotherapy of patients whose response to conventional treatment has proved unsatisfactory. The purpose of this review paper is to present current research on the use of ketamine in the prevention of postpartum depression, including its mechanisms of action, the results of clinical trials to date, and the potential benefits and risks of its use in this specific group of patients.
Brief description of the state of knowledge: Both ketamine and esketamine are used in Poland in the pharmacotherapy of drug-resistant depression. In specialized psychiatric centers it is possible to use the drug off-label (ketamine) in the form of intravenous infusion. A therapeutic option approved by the EMA and the Polish Office for Registration of Medicinal Products is esketamine in intranasal form. Currently, there are no clear recommendations in the context of the use of either substance in postpartum depression.
Summary: The number of new-onset depressive episodes, including postpartum depression, is growing in the world. The clinical condition of the patient affects many aspects of her life, especially the care of the newborn in the first weeks of the child's life. New therapeutic options are key to preventing PPD as well as achieving remission.
Material and methods: A comprehensive literature review was conducted using PubMed, focusing on articles and research papers published between 2020 and 2025
References
[1] Emily B. Kroska Postpartum Depression: Identification and Treatment in the Clinic Setting https://doi.org/10.1016/j.ogc.2020.05.001
[2] Dan Stein Mental(2020), behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies. https://doi.org/10.1186/s12916-020-1495-2
[3] Cafiero PJ, Justich Zabala P. Postpartum depression: Impact on pregnant women and the postnatal physical, emotional, and cognitive development of their children. An ecological perspective. Arch Argent Pediatr 2024;122(3):e202310217. https://doi.org/10.5546/aap.2023-10217.eng
[4] Dominiak, Monika, Anna Z. Antosik-Wójcińska, Marta Baron, Paweł Mierzejewski, and Łukasz Święcicki. 2021. “Recommendations for the Prevention and Treatment of Postpartum Depression.” Ginekologia Polska 92 (2): 153–64. https://doi.org/10.5603/gp.a2020.0141
[5] Ceriani Cernadas JM. Postpartum depression: Risks and early detection. Arch Argent Pediatr 2020;118(3):154-155. http://dx.doi.org/10.5546/aap.2020.eng.154
[6] Dadi, A.F., Miller, E.R. & Mwanri, L. Postnatal depression and its association with adverse infant health outcomes in low- and middle-income countries: a systematic review and meta-analysis. BMC Pregnancy Childbirth 20, 416 (2020). https://doi.org/10.1186/s12884-020-03092-7
[7] Agrawal I, Mehendale A M, Malhotra R (October 31, 2022) Risk Factors of Postpartum Depression. Cureus 14(10): e30898. https://doi.org/10.7759/cureus.30898
[8] Xiao-hu Zhao, Zhi-hua Zhang,Risk factors for postpartum depression: An evidence-based systematic review of systematic reviews and meta-analyses,Asian Journal of Psychiatry,Volume 53,2020,102353,ISSN 1876-2018, https://doi.org/10.1016/j.ajp.2020.102353.
[9] Angarath I. van der Zee-van den Berg, Magda M. Boere-Boonekamp, Catharina G.M. Groothuis-Oudshoorn, Sijmen A. Reijneveld, Postpartum depression and anxiety: a community-based study on risk factors before, during and after pregnancy, Journal of Affective Disorders, Volume 286, 2021, Pages 158-165, ISSN 0165-0327, https://doi.org/10.1016/j.jad.2021.02.062.
[10] Jeleniewska A, Tomaszewska A, Kalicka J, Rustecka A, Kalicki B: The impact of perinatal maternal mental health disorders on the child’s health. Pediatr Med Rodz 2024; 20 (1): 37–43. https://doi.org/10.15557/pimr.2024.0005
[11] Dimcea, D.A.-M.; Petca, R.-C.; Dumitrașcu, M.C.; Șandru, F.; Mehedințu, C.; Petca, A. Postpartum Depression: Etiology, Treatment, and Consequences for Maternal Care. Diagnostics 2024, 14, 865. https://doi.org/10.3390/diagnostics14090865
[12] Kim, Ji-Woon, Kanzo Suzuki, Ege T. Kavalali, and Lisa M. Monteggia. 2024. “Ketamine: Mechanisms and Relevance to Treatment of Depression.” Journal Article. Annual Review of Medicine 75 (Volume 75, 2024): 129–43 https://doi.org/10.1146/annurev-med-051322-120608
[13] Berman, Robert M et al. Antidepressant effects of ketamine in depressed patients
Biological Psychiatry, Volume 47, Issue 4, 351 - 354. https://doi.org/10.1016/s0006-3223(99)00230-9
[14] J.H. Krystal, A.P. Kaye, S. Jefferson, M.J. Girgenti, S.T. Wilkinson, G. Sanacora, & I. Esterlis, Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments, Proc. Natl. Acad. Sci. U.S.A. 120 (49) e2305772120, https://doi.org/10.1073/pnas.2305772120 (2023).
[15] Salahudeen MS, Wright CM, Peterson GM. Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review. Therapeutic Advances in Drug Safety. 2020;11. https://doi.org/10.1177/2042098620937899
[16] Krystal JH, Charney DS, Duman RS. A New Rapid-Acting Antidepressant. Cell. 2020 Apr 2;181(1):7. https://doi.org/10.1016/j.cell.2020.02.033
[17] Hashimoto K. Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochem Pharmacol. 2020 Jul;177:113935. https://doi.org/10.1016/j.bcp.2020.113935
[18] Vasiliu Octavian, Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents, Frontiers in Pharmacology vol. 13 https://doi.org/10.3389/fphar.2022.884155
[19] Fu DJ, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, Hough D, Manji H, Drevets WC, Canuso CM. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). J Clin Psychiatry. 2020 May 12;81(3):19m13191. https://doi.org/10.4088/jcp.19m13191
[20] Ionescu DF, Fu DJ, Qiu X, Lane R, Lim P, Kasper S, Hough D, Drevets WC, Manji H, Canuso CM. Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II). Int J Neuropsychopharmacol. 2021 Jan 20;24(1):22-31. https://doi.org/10.1093/ijnp/pyaa068
[21] Canuso, Carla M. MD∗; Ionescu, Dawn F. MD†; Li, Xiang PhD‡; Qiu, Xin PhD‡; Lane, Rosanne MAS‡; Turkoz, Ibrahim PhD‡; Nash, Abigail I. MD, PhD§; Lopena, Tricia J. PharmD∥; Fu, Dong-Jing MD, PhD∗. Esketamine Nasal Spray for the Rapid Reduction of Depressive Symptoms in Major Depressive Disorder With Acute Suicidal Ideation or Behavior. Journal of Clinical Psychopharmacology 41(5):p 516-524, 9/10 2021. https://doi.org/10.1097/jcp.0000000000001465
[22] Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, George JE, Morrison RL, Sanacora G, Young AH, Kasper S, Sulaiman AH, Li CT, Paik JW, Manji H, Hough D, Grunfeld J, Jeon HJ, Wilkinson ST, Drevets WC, Singh JB. Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). J Clin Psychiatry. 2020 Apr 28;81(3):19m12891. https://doi.org/10.4088/jcp.19m12891
[23] Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A. The effect of ketamine on preventing postpartum depression. J Med Life. 2021 Jan-Mar;14(1):87-92. https://doi.org/10.25122/jml-2020-0116
[24] Han, Y., Li, P., Miao, M. et al. S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: a randomized controlled trial. BMC Anesthesiol 22, 49 (2022). https://doi.org/10.1186/s12871-022-01588-7
[25] Yao J, Song T, Zhang Y, Guo N, Zhao P. Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: A double-blind, randomized clinical trial. Brain Behav. 2020 Sep;10(9):e01715. https://doi.org/10.1002/brb3.1715
[26] Wang, Y., Zhang, Q., Dai, X., Xiao, G., & Luo, H. (2021). Effect of low-dose esketamine on pain control and postpartum depression after cesarean section: a retrospective cohort study. Annals Of Palliative Medicine, 11(1), 45-57. https://dx.doi.org/10.21037/apm-21-3343
[27] Jia-Hui Ma, Sai-Ying Wang, He-Ya Yu, Dan-Yang Li, Shi-Chao Luo, Shan-Shan Zheng, Li-Fei Wan, Kai-Ming Duan, Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section, Psychiatry Research, Volume 279, 2019. https://doi.org/10.1016/j.psychres.2019.03.026
[28] Wang W, Xu H, Ling B, Chen Q, Lv J, Yu W. Effects of esketamine on analgesia and postpartum depression after cesarean section: A randomized, double-blinded controlled trial. Medicine (Baltimore). 2022 Nov 25;101(47):e32010. https://doi.org/10.1097/md.0000000000032010
[29] Kim J, Farchione T, Potter A, Chen Q, Temple R. Esketamine for Treatment-Resistant Depression - First FDA-Approved Antidepressant in a New Class. N Engl J Med. 2019 Jul 4;381(1):1-4. https://doi.org/10.1056/nejmp1903305
[30] Xu, S., Yang, J., Li, J. et al. Esketamine pretreatment during cesarean section reduced the incidence of postpartum depression: a randomized controlled trail. BMC Anesthesiol 24, 20 (2024). https://doi.org/10.1186/s12871-023-02398-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Daria Stefaniak, Michał Chról, Weronika Zielińska, Aleksandra Warunek, Gabriela Gronowicz, Joanna Wanat, Izabela Dzikowska, Wojciech Homa, Agata Siejka

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 151
Number of citations: 0