Antidepressants and Miscarriage Risk
Methods: Using a nested case–control study design, we obtained data from the Quebec Pregnancy Registry for 5124 women who had a clinically detected spontaneous abortion. For each case, we randomly selected 10 controls from the remaining women in the registry who were matched by the case's index date (date of spontaneous abortion) and gestational age at the time of spontaneous abortion. Use of antidepressants was defined by filled prescriptions and was compared with nonuse. We also studied the classes, types and doses of antidepressants.
Results: A total of 284 (5.5%) of the women who had a spontaneous abortion had at least one prescription for an antidepressant filled during the pregnancy, as compared with 1401 (2.7%) of the matched controls (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.83–2.38). After adjustment for potential confounders, we found that the use of antidepressants during pregnancy was associated with an increased risk of spontaneous abortion (OR 1.68, 95% CI 1.38–2.06). Stratified analyses showed that use of selective serotonin reuptake inhibitors alone (OR 1.61, 95% CI 1.28–2.04), serotonin–norepinephrine reuptake inhibitors alone (OR 2.11, 95% CI 1.34–3.30) and combined use of antidepressants from different classes (OR 3.51, 95% CI 2.20–5.61) were associated with an increased risk of spontaneous abortion. When we looked at antidepressant use by type versus no use, paroxetine use alone (OR 1.75, 95% CI 1.31–2.34) and venlafaxine use alone (OR 2.11, 95% CI 1.34–3.30) were associated with an increased risk of spontaneous abortion.
Interpretation: The use of antidepressants, especially paroxetine, venlafaxine or the combined use of different classes of antidepressants, during pregnancy was associated with an increased risk of spontaneous abortion.
From press release:
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 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.
Hamid Reza Nakhai-Pour, Perrine Broy, Anick Bérard.
Use of antidepressants during pregnancy and the risk of spontaneous abortion
Can. Med. Assoc. J.
Faculty of Pharmacy, University of Montreal, Montréal, Que.;