Untreated Maternal MDD May Outweigh SSRI Risks in Pregnancy
Key Takeaways for Clinical Practice
- A JAMA Psychiatry Special Communication concludes that selective serotonin reuptake inhibitors (SSRIs) carry little or no risk for the most serious adverse outcomes after accounting for major depressive disorder (MDD) and related confounding.
- Untreated maternal depression is independently associated with adverse pregnancy, neonatal, and child outcomes.
- Clinicians should use structured, individualized decision-making that weighs treatment benefits, illness-related risks, medication exposure, and patient preferences.
Treating MDD during pregnancy should be prioritized as part of maternal and fetal health care, argued the authors of a Special Communication published in JAMA Psychiatry.
In the United States, approximately 5% to 6% of pregnant patients receive SSRIs, most commonly for MDD, which affects about 12% of pregnant patients.
Study Findings
The authors reviewed evidence on maternal MDD, SSRI treatment, and pregnancy and offspring outcomes. They concluded that many associations previously attributed to antidepressant exposure are substantially explained by the underlying depressive disorder and associated clinical and social factors.
MDD itself is associated with increased pregnancy risks. Compared to women without depression, women with MDD had higher odds of preterm birth, with an odds ratio of 1.46, and low birth weight, with an odds ratio of 1.90. Cesarean delivery was 3.5 percentage points more common, and hyperemesis gravidarum was associated with an odds ratio of 5.2.
Evidence on antidepressant discontinuation also suggests clinically relevant relapse risk. In one perinatal psychiatry program cited in the article, patients who discontinued medication relapsed significantly more often than those who maintained treatment, with a hazard ratio of 5.0. A meta-analysis found relapse risk was especially elevated among women with severe or recurrent depression.
The review nevertheless identifies potential treatment-associated effects. Poor neonatal adaptation signs occur in up to 30% of newborns exposed prenatally to SSRIs, although the condition is generally self-limited and typically resolves within 2 weeks with supportive care.
Clinical Implications
The authors emphasize that pregnancy does not present a zero-risk treatment choice. Instead, clinicians must compare potential medication risks with the risks of untreated or undertreated depression, while recognizing that observational research cannot completely exclude small or moderate medication-related effects.
SSRIs remain first-line medications and an essential component of perinatal depression care, particularly where psychotherapy or specialty services may be difficult to access. The authors recommend structured counseling that presents absolute risks when possible, acknowledges uncertainty, and incorporates patient values and preferences.
Expert Commentary
“The separation of MDD from other medical disorders represents stigma rather than science,” wrote Katherine L. Wisner, MD, MS, Children’s National Hospital and George Washington University School of Medicine, Washington, DC, and coauthors. The authors call for expanded access to perinatal mental health care and further research to improve individualized treatment across pregnancy and the postpartum period.
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