SSRI and Other Antidepressants and Pregnancy – 2020

Peter ForsterMajor Depression, Physical Conditions and Health, Treatments of Depression Leave a Comment

We have several other posts on this topic which trace the evolution of our thinking about the risks of using antidepressants during pregnancy.

Generally, the data continues to support our view that the risks of depression during pregnancy, both in terms of effects on the mother and effects on the child, usually outweigh the risks of antidepressant use.

Another large study, this time looking at data from more than 30,000 pregnancies, supports this assessment, and adds to data about specific antidepressants that may have an increased risk of adverse effects on the child.

The study is a case control study, which has some limitations but allows us to examine large numbers of patient outcomes. It compared mothers of infants with birth defects to mothers of infants without birth defects. The main challenge in these studies is controlling for factors other than antidepressant exposure that may be linked to birth defects. As an example, women who have been treated with antidepressants usually have a history of depression, and a history of depression is associated with an increased risk of obesity, alcohol use, smoking, and a host of secondary factors (called confounding variables) that may, in turn, lead to more birth defects.

Overall, the results were reassuring. When controlling for known confounding variables there were few statistically significant associations and those that did exist were not clinically significant (a small increased risk would be outweighed by the known adverse effects of depression). The authors also noted that the data did not allow them to control for many potential confounding variables, for example they could not control for symptom severity, which would be expected to guide selection of an antidepressant.

“Case” means a woman with a child with a birth defect. Compare the percentages (in parentheses) of women with and without a birth defect for each medication. A difference of 0.1 % was not likely to be clinically significant. For many medications the numbers were too small to assess (duloxetine, desvenlafaxine, TCA’s).

The authors did note that there was some preliminary evidence that women treated with venlafaxine had a higher risk of birth defects. The reason I am skeptical about this is that venlafaxine is usually prescribed for women with more severe and/or more chronic depression, and the authors could not assess for this potential confounding factor.

In an accompanying editorial, Katherine Wisner, et al, summarize the state of our knowledge…

A growing awareness of the fetal and early life origins of mental health highlights the importance of prevention and early intervention to mitigate the consequences of maternal psychiatric illness during childbearing. Avoidance of medication is not an option for some women. Conceptualizing the literature on the effect of both depression and antidepressant exposure during pregnancy requires an appreciation of their extraordinary and complex interrelated dimensions. In women treated with SSRI, depressive symptoms range from remission to full syndromal depression. Even women who have no current symptoms continue to be vulnerable, similar to a woman who has well-controlled diabetes who does not have the same overall health risk as a woman without diabetes. The evidence accumulated over the past 2 decades points to the risk (if any) for birth defects associated with antidepressants to be acceptable compared with the risks of untreated or undertreated maternal depression. Looking ahead, we must direct our research to advance the sophistication of treatment decision-making. 

Katherine L. Wisner, MD, MS; Tim F. Oberlander, MD, FRCPC; Krista F. Huybrechts, MS, PhD

For More Information

SSRI and Pregnancy 2016

Pregnancy and Mental Health


Anderson KN, Lind JN, Simeone RM, et al. Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects. JAMA Psychiatry. 2020;77(12):1246–1255. doi:10.1001/jamapsychiatry.2020.2453

Wisner KL, Oberlander TF, Huybrechts KF. The Association Between Antidepressant Exposure and Birth Defects—Are We There Yet? JAMA Psychiatry. 2020;77(12):1215–1216. doi:10.1001/jamapsychiatry.2020.1512