MedicalResearch: What are the main findings of the study?
Dr. Huybrechts: In this cohort study including 949,504 pregnant women enrolled in Medicaid, we 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. 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. We found no substantial increased risk of cardiac malformations attributable to SSRIs. Relative risks for any cardiac defect were 1.25 (95%CI, 1.13-1.38) unadjusted, 1.12 (1.00-1.26) depression-restricted, and 1.06 (0.93-1.22) depression-restricted and fully-adjusted. We 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); two potential associations that had been of particular concern based on previous research findings.
MedicalResearch: Were any of the findings unexpected?
Dr. Huybrechts: In 2005, based on early results of two epidemiologic studies, the 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. We designed the study to test one specific hypothesis with enough statistical power, while minimizing biases. We did not know a priori whether we were going to confirm or refute the hypothesis. Our results do not support earlier findings of an association between antidepressants and cardiac anomalies, in particular for paroxetine and sertraline.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. 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. Our results suggest that first trimester use of antidepressants does not substantively increase the risk of specific cardiac defects. The accumulated evidence implies low absolute risks and argue against the existence of important cardiac teratogenic effects for the most commonly used antidepressant medications.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Huybrechts: This study addresses only one piece of the complex puzzle about the safety of antidepressants during pregnancy. More research is necessary to evaluate the risks and benefits of using these medications during pregnancy for both women and their newborns, including outcomes such as pre-term birth and neonatal withdrawal, and the safety issues that can result from withholding a needed treatment in pregnant women with severe depression that requires medication.