First trimester antidepressant use and miscarriage: a comprehensive analysis in the Clinical Practice Research Datalink GOLD

Br J Gen Pract. 2025 Aug 7:BJGP.2025.0092. doi: 10.3399/BJGP.2025.0092. Online ahead of print.

ABSTRACT

Background Antidepressant prescribing during pregnancy is rising but uncertainties remain surrounding safety. Evidence relating to antidepressant use during pregnancy and miscarriage ranges in quality. Aim To investigate the association between first trimester antidepressant use and miscarriage. Design and setting Population-based cohort study in the UK Clinical Practice Research Datalink (CPRD) GOLD. Methods We identified pregnancies in the CPRD GOLD Pregnancy Register between 1996-2018. Pregnancies with prescriptions of antidepressants overlapping with first trimester were defined as ‘exposed’ and were compared to unexposed using Cox models, calculating adjusted hazard ratios (aHR) and absolute risk of miscarriage adjusted for confounders including depression, anxiety, smoking, and other health, lifestyle, and obstetric factors. Results Among the 1,021,384 eligible pregnancies, 73,540 were prescribed antidepressants in trimester one (7.2%); 14.7% antidepressant prescribed pregnancies ended in miscarriage versus 12.4% of those not prescribed antidepressants. Antidepressant use during trimester one was associated with miscarriage in the unadjusted models (HR 1.21, 95% confidence interval (CI) 1.19-1.23), which attenuated following adjustment for covariates (aHR 1.04, 95%CI 1.02-1.06). These findings translated to an absolute risk adjusted for confounders of 13.1% (95%CI 13.0-13.2) among unexposed and 13.6% (95%CI 13.3-13.8) among exposed. Among those taking antidepressants in the three months prior to pregnancy and into trimester one, the risk of miscarriage was the same as among unexposed (aHR 1.00, 95%CI 0.98-1.03). Conclusion First trimester antidepressant use was associated with a small, clinically insignificant increased risk of miscarriage, with no evidence suggesting taking antidepressants before pregnancy and into first trimester increases the risk of miscarriage.

PMID:40774797 | DOI:10.3399/BJGP.2025.0092