Antidepressants in the first trimester – how risky are they?

Antidepressants have become a particular issue as their use has increased, and as awareness of perinatal mental health has improved. We now understand much more about the risks associated in either untreated PNMH condition, or in stopping existing treatment during pregnancy. Pregnancy and the first year afterwards are a risk period for exacerbation of some mental health problems, and the NICE guidelines advise individual conversations with patients. The UK Tetralogy Information Service specifically states the importance of ensuring maternal mental health conditions are treated appropriately, and the MBRRACE-UK reports demonstrate clearly the impact of mental health issues on both Mum, baby and wider family. 

This paper on first-trimester antidepressant use and miscarriage risk, published in the BJGP, adds further reassurance to taking a patient-first approach in this area, and helps bring clarity and context to decisions about continuing or starting antidepressants in early pregnancy.

The research looked at more than one million UK pregnancies via a population-based cohort study. The authors used multiple methods to adjust for the impact of confounding factors like underlying depression, anxiety, smoking, and other health factors. The overall risk of miscarriage occurring in those on anti-depressants was 13.6%, versus 13.1% in unexposed pregnancies. Perhaps most importantly, for those already on antidepressants before conception and continuing into the first trimester, no additional miscarriage risk was observed. 

The authors concluded that this represents a small, but clinically insignificant increased risk. The absolute risk difference is minimal, and particularly continuing existing treatment appears to confer no additional risk. Interestingly, the study looked at all types of antidepressants including SSRIs, TCA, SNRIs and “other”. For many of us working in general practice, we are unlikely to reach for a tricyclic antidepressant first line, especially in a woman who is trying to conceive or already pregnant. The absolute risk was marginally higher in those women taking TCAs or “other” medication (other included mirtazapine, trazodone, phenelzine and numerous other non-1^st line medications). 

Balancing Risks and Benefits

Evidence supports a very modest increase in miscarriage risk with first-trimester antidepressant use—but the absolute difference is tiny. Continuing established, pre-conception therapy appears particularly low risk so we should ensure women receive individual advice, and not a blanket “you must stop your anti-depressants if you become pregnant”. Equally if a woman presents having found out she is pregnant, and has stopped her medication herself, further discussion about the balance of risks is needed. 

NICE underlines the importance of managing maternal depression effectively, even during pregnancy. Untreated or poorly managed depression poses significant risks to both mother and child. Medication choices should be individualised. Sertraline is often recommended as first line for both before, during and after pregnancy, but continuing a previously effective and tolerated agent is valid—especially if that avoids destabilising mental health.

Shared decision-making and specialist involvement are crucial. Choices about continuation, tapering, switching, or suspending treatment should involve clear discussions, informed consent, and, if needed, support from your local perinatal mental health team.