Antidepressants in pregnancy: A closer look at miscarriage risk

Today, we’re speaking to Flo Martin, an honorary research associate at the University of Bristol.

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

Available at: https://doi.org/10.3399/BJGP.2025.0092

Antidepressant use during pregnancy is rising, with concerns from pregnant women that these medications may increase the risk of miscarriage if taken prenatally. Evidence is conflicting so we used the Clinical Practice Research Datalink, a large repository of UK-based primary care data, and a range of methods to investigate antidepressant use during trimester one and risk of miscarriage.

Transcript

This transcript was generated using AI and has not been reviewed for accuracy. Please be aware it may contain errors or omissions.

Speaker A

00:00:00.240 - 00:00:52.800

Hello and welcome to BJJP Interviews. I'm Nada Khan and I'm one of the associate editors at the bjgp. Thanks for taking the time today to listen to this podcast.

In today's episode, we're speaking to Dr. Flo Martin, an honorary research associate at the University of Bristol.

We're here to look at the paper she's recently published here in the BJGP titled First Trimester Antidepressant Use and Miscarriage A Comprehensive Analysis in the Clinical Practice Research Data Link. Gold. So, hi, Flo, it's great to meet you and talk about this research.

And I think this paper touches on an area that clinicians and women often approach with a bit of uncertainty, just in terms of prescribing safety, really, in pregnancy in general. But can you talk us through what we know already about prescribing for antidepressants and risk in pregnancy, just to frame what you've done here?

Speaker B

00:00:53.280 - 00:02:22.860

Yeah, absolutely.

So we actually did some work a couple of years ago doing a systematic review of the literature in this space, so looking at antidepressant use during pregnancy and the risk of miscarriage. And the work spanned the last kind of 30 years.

And what we found was a 30% increase in risk of miscarriage following antidepressant use during pregnancy. And this was obviously kind of alarming to see this increase in risk. But the kind of key takeaway from the paper was not actually this finding.

It was mostly the kind of variation in the literature that we observed when answering this question.

We kind of were very cautious about interpreting this 30% increase in risk as a kind of true causal effect because we had observed these other things that might be driving the estimate kind of upwards and might not necessarily show the true effect that was happening in this population. So that was kind of the environment that we were existing in before we started the study.

And it really informed the way that we wanted to do this study.

So we thought it was really important to try and understand that baseline risk in both unexposed and exposed pregnancies, so that whatever we observed was contextualized against what the underlying risk was among those who hadn't been prescribed antidepressants.

Speaker A

00:02:23.500 - 00:02:58.120

Yeah, fair enough.

So this is a large analysis of the clinical practice research data link, and you looked at pregnancies between 1996 and 2016 and then followed up women who had been prescribed or not antidepressants and risk of miscarriage.

And I think if people are specifically interested in how you did this, they can go back to the paper and look at some of the different methods you used. But I wanted to focus really on what you found here.

And I think the first thing to point out is that it wasn't uncommon for women to have a prescription for an antidepressant in that first trimester of pregnancy. So talk us through that.

Speaker B

00:02:58.440 - 00:03:43.270

Yeah, exactly. So I think we. We kind of report about 7% of the pregnancies in our study that had been prescribed antidepressants.

And I think, as you say, this is, you know, potentially higher than what you would expect. I think there are kind of multiple things driving this.

If we look outside of pregnancy and kind of zoom out and look at the prescribing rates of antidepressants in both men and women, we can see it's going up, you know, between the 1990s and the late sort of 20 teens. And.

And I think, yeah, people will be maybe surprised to see, but it's very, you know, on trend with what we're seeing outside of pregnancy and then looking.

Speaker A

00:03:43.270 - 00:03:45.950

Specifically at the risk of miscarriage here. What did you find?

Speaker B

00:03:47.150 - 00:04:59.060

Yeah, so when we applied our kind of primary analysis where we were looking at pregnancies who had been prescribed antidepressants in trimester one, and comparing them to pregnancies who were not prescribed antidepressants in trimester one, we found a very, very small increase in relative risk. So I think we found about 4% increase in risk of miscarriage among the prescribed group than. Than the non prescribed.

And what this translated to in terms of that baseline risk, we observed 13.1% of those not prescribed antidepressants, they experienced a miscarriage, and this increased to 13.6% among those who were prescribed. So I think that really puts into perspective when we talk about increases in risk, this is an incredibly modest one, an increase all the same.</p