Selective serotonin reuptake inhibitors during pregnancy: Navigating the complex safety landscape

Abstract

The safety of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has become a contentious issue in clinical practice, particularly following a controversial Food and Drug Administration panel in July 2025 that questioned established safety data. This debate occurs against the backdrop of a mental health crisis affecting up to 20% of pregnant women, where mental health conditions, including suicides and drug overdoses, are now the leading cause of pregnancy-related deaths, according to a 2024 Centers for Disease Control and Prevention report. The challenge lies in balancing the well-documented risks of untreated maternal depression against potential, although small, medication-related risks to the developing fetus.

The current scientific consensus, supported by extensive research spanning decades, demonstrates that SSRIs are generally safe during pregnancy. Robust evidence has shown that SSRIs are safe in pregnancy and that most do not increase the risk of birth defects, according to the American College of Obstetricians and Gynecologists. Recent systematic reviews indicate that perinatal SSRI exposure does not increase the risk of major malformations or gestational diabetes after accounting for underlying maternal illness. While some studies suggest small increased risks of specific complications, including pre-eclampsia, postpartum hemorrhage, preterm delivery, persistent pulmonary hypertension of the newborn, and neonatal intensive care unit admissions – the absolute risk of these outcomes remains low. The most common concern is neonatal adaptation syndrome, affecting approximately 30% of babies whose mothers take SSRIs, causing increased jitteriness, irritability, and respiratory distress, though symptoms typically resolve on their own.

Critically, the risks of untreated maternal depression often outweigh medication risks. Untreated depression in pregnancy can put patients at risk for substance use, preterm birth, pre-eclampsia, limited engagement in medical care and self-care, low birth weight, impaired attachment with their infant, and even suicide. Large-scale studies provide reassurance: A study from Suarez et al., analyzed data from nearly 150,000 children with prenatal antidepressant exposure and found no association between prenatal exposure to antidepressants and risk for neurodevelopmental disorders. Multiple medical organizations have criticized the recent FDA panel for presenting a biased view that focused mainly on the dangers of SSRIs during pregnancy but ignored or diminished the risks associated with untreated depression in the mother. The clinical decision to use SSRIs during pregnancy should involve individualized risk-benefit analysis, considering maternal mental health history, severity of symptoms, and patient values. Women, together with their healthcare providers, weigh the potential benefits of treatment against possible risks associated with a particular medication, informed by the best available scientific evidence, illness and treatment history, and the values and preferences of each woman. Rather than avoiding treatment due to exaggerated fears, healthcare providers should engage in evidence-based counseling that acknowledges both the substantial risks of untreated maternal depression and the generally favorable safety profile of SSRIs, ensuring that women receive appropriate mental health care during this vulnerable period.