SSRIs in pregnancy not linked to cardiac defects in babies

In pregnancy, first trimester use of antidepressants does not substantively increase the risk of specific cardiac defects in babies, and should not be an important consideration in the treatment decision, according to a study published in the June 19 issue of the New England Journal of Medicine.

In a cohort study (nested in the nationwide Medicaid Analytic eXtract [MAX]) including 949,504 pregnant women enrolled in Medicaid, Krista F. Huybrechts, MS, PhD, and colleagues examined whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants during the first trimester of pregnancy is associated with increased risks for congenital cardiac defects.

“We compared the risk of major cardiac defects in women with antidepressant medication use during the first trimester versus no use,” said Huybrechts, assistant professor of medicine, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston.

“In order to control for potential confounding by depression and associated factors, we restricted the cohort to women with a depression diagnosis and used propensity score adjustment to control for depression severity and other potential confounders,” she said. 

The researchers found no substantial increased risk of cardiac malformations attributable to SSRIs: the relative risk for any cardiac defect was 1.06 (95% CI, 0.93-1.22). In addition, they found no significant associations between the use of paroxetine and right ventricular outflow tract obstruction (1.07, 0.59-1.93), or the use of sertraline and ventricular septal defects (1.04, 0.76-1.41); 2 potential associations that had been of particular concern based on previous research findings.

“We conducted the study to shed light on one of the potential adverse effects associated with first trimester antidepressant medication use,” said Huybrechts.

“Decisions by clinicians and women about whether to continue or discontinue treatment with antidepressants during pregnancy must balance potential risks of treatment with the risks of not treating women with severe depression,” she said.  “Our results suggest that first trimester use of antidepressants does not substantively increase the risk of specific cardiac defects, and should not be an important consideration in the treatment decision.

"The accumulated evidence implies low absolute risks and argue against the existence of important cardiac teratogenic effects for the most commonly used antidepressant medications," she continued. "However, it should be emphasized that this study addresses only one piece of the complex puzzle about the safety of antidepressants during pregnancy.”

In 2005, based on early results of 2 epidemiologic studies, FDA warned healthcare professionals that early prenatal exposure to paroxetine may increase the risk of congenital cardiac malformations.  Since then, several studies have evaluated the teratogenicity of SSRIs and other antidepressants.  Existing studies have reported different associations, often in the context of multiple comparisons.

“It has remained unclear, however, whether these associations are causal, or due to systematic error or chance,” Huybrechts said.  “We designed the study to test one specific hypothesis with enough statistical power, while minimizing biases.”