Evidence challenges long-standing concerns about SSRIs in pregnancy

Clinical takeaway: Do not discontinue an effective SSRI solely because of pregnancy without considering depression severity and relapse risk. Counseling should weigh potential medication risks against the established risks of untreated or undertreated depression.

Concerns about fetal exposure can complicate antidepressant treatment decisions during pregnancy. But focusing on medication risk alone misses an important part of the equation: major depressive disorder (MDD) itself can adversely affect maternal, pregnancy, and child outcomes.

In a Special Communication in JAMA Psychiatry, experts reviewing the accumulated evidence argue that selective serotonin reuptake inhibitors (SSRIs) remain an essential component of perinatal mental health care. Once researchers better account for underlying depression and related factors, SSRIs appear to carry little or no additional risk for the most serious maternal and offspring outcomes.

Earlier studies raised concerns about congenital cardiac defects and autism spectrum disorder after prenatal SSRI exposure. Larger and more rigorous studies have substantially weakened or eliminated many of these associations after accounting for maternal MDD, genetic and familial factors, and other confounders. The authors conclude that the overall evidence does not support SSRIs as a cause of congenital malformations or autism, although small risks cannot be completely excluded.

SSRI exposure is not risk-free. Poor neonatal adaptation signs, including jitteriness, respiratory distress, irritability, and feeding problems, occur in up to 30% of exposed newborns, but are generally self-limited and resolve within two weeks with supportive care. Some evidence also suggests small increases in persistent pulmonary hypertension of the newborn or preterm birth.

Those potential risks must be weighed against undertreatment. Maternal depression is independently associated with pregnancy complications and adverse child outcomes, and stopping antidepressants can increase relapse risk, particularly in patients with severe or recurrent depression.

The authors recommend individualized, structured decision-making that considers illness severity, previous treatment response, relapse risk, patient preferences, and both maternal and fetal outcomes rather than treating medication avoidance as the default.

“No zero-risk option exists,” the authors wrote, emphasizing that treatment decisions should compare the best available estimates of SSRI risk with those of the underlying illness and its consequences.

Source: Wisner KL, et al. (2026 Aug 12) JAMA Psychiatry. Depression and SSRI treatment during pregnancy—prioritizing maternal mental health