First-Trimester Antidepressants Show Least Miscarriage Risk

TOPLINE:

The use of antidepressants during the first trimester was associated with a small but clinically insignificant increase in the risk for miscarriage; however, no evidence existed to suggest that their use prior to pregnancy and into the first trimester was associated with an increased risk.

METHODOLOGY:

• Researchers conducted a population-based cohort study using the UK Clinical Practice Research Datalink GOLD database to evaluate the association between antidepressant use during the first trimester and the risk for miscarriage.
• They included 1,021,384 eligible singleton pregnancies with known outcomes between 1996 and 2018; participants were registered at up-to-standard practices and had at least 1 year of follow-up before and through the end of pregnancy.
• Researchers identified all antidepressants approved for treating depression in the UK and classified them on the basis of class.
• Pregnancies with an antidepressant prescription overlapping with the first trimester were defined as exposed (the exposed group) and compared with those without antidepressant exposure (the unexposed group).

TAKEAWAY:

• Of the 1,021,384 eligible pregnancies, 73,540 (7.2%) were prescribed antidepressants during the first trimester.
• Of 967,925 pregnancies with complete covariate data, 71,460 received antidepressants during the first trimester, with 14.6% of pregnancies vs 12.3% of 896,465 unexposed pregnancies being resulted in miscarriage (hazard ratio [HR], 1.21; 95% CI, 1.19-1.23).
• After adjusting for covariates, these effects attenuated (adjusted HR [aHR], 1.04; 95% CI, 1.02-1.06), with a standardised miscarriage risk of 13.6% (95% CI, 13.3%-13.8%) in the exposed group and 13.1% (95% CI, 13.0%-13.2%) in the unexposed group.
• Among women who were prescribed antidepressants at 3 months prior to pregnancy, the risk for miscarriage did not differ between those who continued antidepressants into the first trimester and those who discontinued before pregnancy (aHR, 1.00; 95% CI, 0.98-1.03).

IN PRACTICE:

“The findings are reassuring for prescribing clinicians and individuals concerned about antidepressant use during early pregnancy and miscarriage, providing both parties with robust supportive evidence for informed decision-making in clinic,” the authors wrote.

SOURCE:

This study was led by Florence Zoe Martin, MSc, PhD student, MRC Integrative Epidemiology Unit, University of Bristol Medical School, Bristol, England. It was published online on August 07, 2025, in the British Journal of General Practice.

LIMITATIONS:

Despite adjusting for depression and anxiety and restricting to those with recent or severe illness, residual confounding by the underlying severity of indication likely contributed to the results. Because the gestational length was imputed more often for losses than for deliveries, pregnancies ending in miscarriage may have been more frequently misclassified as exposed than those ending in delivery. Those seeking healthcare for depression, anxiety, or other conditions treated with antidepressants may have been more likely to report pregnancies and early losses than those not engaged with healthcare for other reasons.

DISCLOSURES:

Several authors reported receiving support from various institutions and organisations including the Wellcome Trust, National Institutes of Health, Medical Research Council, and others.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.