DOI: 10.1001/jamapsychiatry.2026.2405 ISSN: 2168-622X

Depression and SSRI Treatment During Pregnancy—Prioritizing Maternal Mental Health

Katherine L. Wisner, Tim F. Oberlander, Lauren M. Osborne, Krista F. Huybrechts

Importance

In the US, 5% to 6% of pregnant patients are treated with selective serotonin reuptake inhibitors (SSRI), primarily for major depressive disorder (MDD), which has a prevalence of about 12%. Psychiatric conditions are a leading cause of maternal morbidity and mortality. MDD is a common disorder that must be treated during pregnancy to improve outcomes for the mother, infant, family, and community.

Observations

MDD is a complex, multifactorial brain disease arising from genetic, environmental, and epigenetic factors. Factors unique to the perinatal period are associated with additional pathophysiologic changes specific to MDD. Maternal stress and psychiatric illnesses adversely affect fetal and infant outcomes. SSRI are an essential component of perinatal mental health care. Studies that define the benefits of SSRI treatment in pregnancy are fewer than those defining risks; however, several describe adverse effects with drug discontinuation in women with moderate to severe MDD. Evaluating the safety of SSRI treatment during pregnancy has been challenging due to the potential for confounding in observational studies by the underlying indication and associated factors. Once the impact of the drug is disentangled from that of MDD and its sequelae, accumulated evidence suggests that SSRI carry little or no risk for serious adverse outcomes. The thrust of the field has shifted to prioritize treatment of MDD to optimize maternal health.

Conclusions and Relevance

Meaningful advances in the treatment of perinatal MDD require coordinated attention to multiple aspects of clinical care delivery and research, informed by a perspective accounting for the health needs of 2 generations. Expanding access to care—particularly in maternity, child health, and psychiatric care deserts—is a public health imperative. A structured decision-making process facilitates the provision of balanced information on the potential maternal and fetal risks of untreated or undertreated illness, the benefits of treatment, and the risks associated with SSRI exposure.

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