Yet Another Study: Antidepressants Do Not Increase Risk of Miscarriage

Many women ask whether taking antidepressants may increase the risk for miscarriage or spontaneous abortion.  Some earlier studies have demonstrated an increased risk of miscarriage among women who use antidepressants. However, it is difficult to determine whether this increased risk observed in the earliest studies is related to exposure to the medication itself, or whether increased risk of miscarriage may be attributable to exposure to other risk factors, including maternal depression.  Many of these early studies were unable to separate these two possibilities, as they compared rates of miscarriage in women taking antidepressants to rates of miscarriage in healthy women without a history of depression.  

Over the last decade we have seen several different systematic reviews and meta-analyses examining the risk of miscarriage in women using antidepressants.  The most recent meta-analysis from Smith and colleagues analyzed data from 29 studies including over 5 million individuals

In the unadjusted analysis of the data, it appeared that antidepressant users had a higher risk of miscarriage compared to unexposed individuals from the general population (summary effect estimate: 1.24, 95% CI 1.18 to 1.31).  However, the difference was diminished when they compared risk of miscarriage in antidepressant users to risk in unexposed individuals with maternal depression (1.16, 1.04 to 1.31).  This finding suggests that confounding by indication may be driving the association between antidepressant exposure and miscarriage seen in earlier studies.  

This finding is consistent with previous meta-analyses and other studies which were large enough to adjust for potential confounding factors.  In these studies, unadjusted analyses show an association between antidepressant use and risk of miscarriage.  This association decreases or disappears after accounting for potential confounding factors.  

Risk of Miscarriage in Women Who Maintain Versus Discontinue Antidepressants

Perhaps one of the most elegant and persuasive studies examining the risk of miscarriage in women using antidepressant is from Andersen and colleagues. Analyzing data from the Danish medical registers, they identified 22,884 women who used an SSRI antidepressant during the first 35 days of pregnancy.  Compared to unexposed women, those who had used an antidepressant early in pregnancy had a small increase in risk of miscarriage, with an adjusted odds ratio (OR) of 1.27 (95% confidence interval [CI] 1.22-1.33).

However, the researchers also found that women who discontinued SSRI treatment 3–12 months, 6–12 months, or 9–12 months before pregnancy had essentially the same risk of having a miscarriage as women using SSRI antidepressants during pregnancy.  This finding suggests that there is no causal relationship between use of SSRIs and miscarriage.  The researchers concluded that underlying psychiatric illness – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Given this large and growing body of research, we can reassure women and their providers that the use of antidepressants does not appear to increase risk for miscarriage.

Ruta Nonacs, MD PhD

References:

Andersen JT, Andersen NL, Horwitz H, Poulsen HE, Jimenez-Solem E. Exposure to Selective Serotonin Reuptake Inhibitors in Early Pregnancy and the Risk of Miscarriage.  Obstet Gynecol. 2014 Sep 5.

Smith S, Martin F, Rai D, Forbes H. Association between antidepressant use during pregnancy and miscarriage: a systematic review and meta-analysis. BMJ Open. 2024 Jan 25;14(1):e074600.