Antidepressants in pregnancy increase risk of miscarriage

A new study in CMAJ (Canadian Medical Association Journal) found a 68% increase in the overall risk of miscarriage in pregnant women using antidepressants.

Antidepressants are widely used in pregnancy and up to 3.7% of women will use them at some point during the first trimester. Discontinuing treatment can result in a depressive relapse which can put mother and baby at risk.

Most previous studies on the use of antidepressants in pregnancy did not look at miscarriages as a main outcome, had small samples and several showed contradictory results. This large study sought to determine the association between antidepressant use in pregnancy, including classes, types and doses, and the risk of miscarriage.

Researchers from the University of Montreal and the CHU Ste-Justine looked at data on 5124 women in Quebec from a large population-based cohort of pregnant women who had clinically verified miscarriages up to 20 weeks of gestation and a large sample of women from the same Registry who did not have a miscarriage. Of those who miscarried, 284 (5.5%) had taken antidepressants during pregnancy.

Selective serotonin reuptake inhibitors (SSRIs), especially paroxetine and also venlafaxine were associated with increased risk of miscarriage as were higher daily doses of either antidepressant. As well, a combination of different antidepressants doubled the risk of miscarriages.

"These results, which suggest an overall class effect of selective serotonin reuptake inhibitors, are highly robust given the large number of users studied," writes senior author Dr. Anick Bérard, from the University of Montreal and the Director of the Research Unit on Medications and Pregnancy at CHU Ste-Justine.

The researchers urge that physicians who have patients of child-bearing age taking antidepressants or have pregnant patients who require antidepressant therapy early in pregnancy discuss the risks and benefits with them.

In a related commentary (pre-embargo link only) http://www.cmaj.ca/embargo/cmaj100507.pdf, Ms. Adrienne Einarson, Assistant Director of the Motherisk Program at The Hospital for Sick Children (SickKids) writes that there is no "gold standard for studying the safety of drugs during pregnancy, because all methods have strengths and limitations," and results can vary from one study to the next. In this study, there were missing data on important potential confounding factors. However, the overall results on the use of antidepressants during pregnancy and the risk of miscarriage, despite the different methodology, were almost identical to a Motherisk study with 937 women published in 2009.

"Clearly, this study cannot make any definitive conclusions as to whether antidepressants increase the risk of spontaneous abortion," although the author points out it appears there is a small risk with less than double the number of miscarriages in the women exposed to antidepressants compared to those not exposed.