SAFETY AND EFFECTIVENESS OF SSRIS AND SNRIS TREATMENT FOR PERINATAL DEPRESSION: A SYSTEMATIC REVIEW
Abstract
Introduction and Purpose: Perinatal depression is a common and serious condition affecting maternal and child health. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are widely used despite ongoing safety concerns. This review aims to evaluate current evidence on the safety and effectiveness of antidepressant treatment during pregnancy and the postpartum period to support individualized clinical decision-making in the management of perinatal depression.
Methods: A narrative systematic review of population-based cohort studies, systematic reviews, and meta-analyses published between 2014 and 2025 was conducted using PubMed. Results: The evidence indicates that SSRIs and SNRIs exposure during pregnancy is associated with small increases in the risk of preterm birth, neonatal adaptation syndrome, postpartum hemorrhage, and rare outcomes such as persistent pulmonary hypertension of the newborn, particularly with late-pregnancy exposure. Absolute risks remain low, and associations with neurodevelopmental disorders largely attenuate after adjustment for familial and maternal psychiatric factors. Postpartum antidepressant treatment is consistently associated with sustained improvements in maternal mental health and functional outcomes.
Conclusions: Current evidence supports individualized risk–benefit assessment when considering antidepressant use during the perinatal period. Maintaining maternal mental health is essential, and treatment decisions should consider illness severity, timing of exposure, and patient preferences.
References
Al-Abri K, Edge D, Armitage CJ. Prevalence and correlates of perinatal depression. Soc Psychiatry Psychiatr Epidemiol. Nov 2023;58(11):1581–1590. doi:10.1007/s00127-022-02386-9 https://pmc.ncbi.nlm.nih.gov/articles/PMC9842219/
Ettman CK, Badillo-Goicoechea E, Stuart EA. Evolution of Depression and Anxiety During the COVID-19 Pandemic and Across Demographic Groups in a Large Sample of U.S. Adults. AJPM Focus. 2023 Aug 12;2(4):100140. doi:10.1016/j.focus.2023.100140. PMID: 37920404; PMCID: PMC10618701. https://pmc.ncbi.nlm.nih.gov/articles/PMC10618701/
Sarkar D, Mandal S, Bandyopadhyay S, Bose S, Parkash J, Singh SK. Use of serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy: Effect on fetal growth and long-term reproductive outcomes. Reprod Toxicol. 2025 Sep;136:108960. doi: 10.1016/j.reprotox.2025.108960. Epub 2025 May 30. PMID: 40451515. https://www.sciencedirect.com/science/article/abs/pii/S0890623825001315?via%3Dihub
McDonagh M, Matthews A, Phillipi C, Romm J, Peterson K, Thakurta S, Guise JM. Antidepressant Treatment of Depression During Pregnancy and the Postpartum Period. Evid Rep Technol Assess (Full Rep). 2014 Jul;(216):1-308. doi: 10.23970/AHRQEPCERTA216. PMID: 30313002. https://journals.lww.com/greenjournal/fulltext/2014/09000/depression_drug_treatment_outcomes_in_pregnancy.8.aspx
Cesta CE, Reutfors J, Cohen JM, Eriksson J, Furu K, Zoega H, Pazzagli L. Postpartum Psychiatric Outcomes and Sick Leave After Discontinuing SSRI or SNRI in Pregnancy. JAMA Netw Open. 2024 Oct 1;7(10):e2438269. doi: 10.1001/jamanetworkopen.2024.38269. PMID: 39378031; PMCID: PMC11581648. https://pmc.ncbi.nlm.nih.gov/articles/PMC11581648/
Sujan AC, Rickert ME, Öberg AS, Quinn PD, Hernández-Díaz S, Almqvist C, Lichtenstein P, Larsson H, D'Onofrio BM. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA. 2017 Apr 18;317(15):1553-1562. doi: 10.1001/jama.2017.3413. PMID: 28418479; PMCID: PMC5875187. https://pmc.ncbi.nlm.nih.gov/articles/PMC5875187/
Bałkowiec-Iskra E, Mirowska-Guzel DM, Wielgoś M. Effect of antidepressants use in pregnancy on foetus development and adverse effects in newborns. Ginekol Pol. 2017;88(1):36-42. doi: 10.5603/GP.a2017.0007. PMID: 28157249.
8.Liu C, Ystrom E, McAdams TA. Long-Term Maternal and Child Outcomes Following Postnatal SSRI Treatment. JAMA Netw Open. 2023 Aug 1;6(8):e2331270. doi: 10.1001/jamanetworkopen.2023.31270. PMID: 37642961; PMCID: PMC10466165. https://journals.viamedica.pl/ginekologia_polska/article/view/48275
Lebin LG, Novick AM. Selective Serotonin Reuptake Inhibitors (SSRIs) in Pregnancy: An Updated Review on Risks to Mother, Fetus, and Child. Curr Psychiatry Rep. 2022 Nov;24(11):687-695. doi: 10.1007/s11920-022-01372-x. Epub 2022 Oct 1. PMID: 36181572; PMCID: PMC10590209. https://pmc.ncbi.nlm.nih.gov/articles/PMC10590209/
Masarwa R, Bar-Oz B, Gorelik E, Reif S, Perlman A, Matok I. Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis. Am J Obstet Gynecol. 2019 Jan;220(1):57.e1-57.e13. doi: 10.1016/j.ajog.2018.08.030. Epub 2018 Aug 28. PMID: 30170040. https://www.ajog.org/article/S0002-9378(18)30709-9/fulltext
Bérard A, Zhao JP, Sheehy O. Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort. BMJ Open. 2017 Jan 12;7(1):e013372. doi: 10.1136/bmjopen-2016-013372. PMID: 28082367; PMCID: PMC5278249. https://pmc.ncbi.nlm.nih.gov/articles/PMC5278249/
Bérard A, Sheehy O, Zhao JP, Vinet É, Bernatsky S, Abrahamowicz M. SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin Pharmacol. 2017 May;83(5):1126-1133. doi: 10.1111/bcp.13194. Epub 2017 Jan 18. PMID: 27874994; PMCID: PMC5401975. https://pmc.ncbi.nlm.nih.gov/articles/PMC5401975/
Dubovicky M, Belovicova K, Csatlosova K, Bogi E. Risks of using SSRI / SNRI antidepressants during pregnancy and lactation. Interdiscip Toxicol. 2017 Sep;10(1):30-34. doi: 10.1515/intox-2017-0004. PMID: 30123033; PMCID: PMC6096863. https://pmc.ncbi.nlm.nih.gov/articles/PMC6096863/
Robiyanto R, Roos M, Bos JHJ, Hak E, van Puijenbroek EP, Schuiling-Veninga CCM. Switching pattern and dose adjustment of antidepressants before and during pregnancy. Arch Womens Ment Health. 2023 Oct;26(5):685-696. doi: 10.1007/s00737-023-01355-8. Epub 2023 Aug 5. PMID: 37542677; PMCID: PMC10491541. https://pmc.ncbi.nlm.nih.gov/articles/PMC10491541/
Copyright (c) 2026 Andrzej Józef Horabik, Paweł Jan Babiński, Magdalena Wiśniewska, Zuzanna Karolina Jędrzejczak, Małgorzata Dmochowska, Julia Hertmanowska, Marta Piotrowska, Krzysztof Chmura, Adrianna Alicja Piekarska, Gabriela Kryger

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

