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.

And it's important to not kind of trivialize that increase in risk.

But I think it's also incredibly reassuring that when we kind of really place it within what the underlying risk is had someone not taken antidepressants, it's very, very small.

Speaker A

00:04:59.620 - 00:05:00.100

Yeah.

Speaker B

00:05:00.180 - 00:06:32.630

Yeah. I think this is a really important piece of the puzzle for risk communication.

Being able to show relative increases in risk, which are incredibly useful alongside what that actually means in terms of the percentage, the proportion of people that experience an outcome, because it just reminds people that, you know, clinicians and patients alike, that this isn't something that you have complete control over. This isn't purely your behavior driven. It's not.

So I think that can be really kind of reassuring for Individuals who feel that kind of burden of risk mitigation.

We see it in Heather James's paper in BJDP last year, a beautiful qualitative study speaking to women who had experienced antidepressant use during pregnancy and talking through their decision making process and their fears and concerns.

And a couple of the participants who were involved in that study cited miscarriage as one of a specific, one of their specific concerns when taking antidepressants during pregnancy and actually discontinued their antidepressants because they were worried about miscarriage.

So these concerns are having direct impacts on individuals and their behaviour and, you know, their potential management of their depression and anxiety.

Speaker A

00:06:33.190 - 00:06:44.230

So, yeah, I think it's important to balance these risks against the mental health risks for the woman who's taking or needing antidepressants. And I think, as you point out, that was demonstrated beautifully in that qualitative research as well.

Speaker B

00:06:44.310 - 00:06:45.030

Definitely.

Speaker A

00:06:45.670 - 00:06:59.990

I wanted to sort of just draw back to how we can use these results in practice, really.

And I wonder what your thoughts are about how clinicians and women should use these findings to inform their decisions around using antidepressants in pregnancy.

Speaker B

00:07:00.950 - 00:08:34.090

Absolutely, yeah. So while I'm hoping that these results, as a non clinician myself, I'm hoping that these results can be informative for decision making.

This isn't the only piece of evidence out there and it shouldn't be considered as the kind of gold standard, because it isn't.

We utilize a lot of methods and comparators, we use large data, we've thought carefully about all of the things that might be driving these effects and discuss them at length. But it's not the only piece of the puzzle.

I'm hoping that these results can help to kind of illuminate what the truth might be and the factors that might be influencing our perception of the results.

So understanding data, understanding methods that will make us kind of rightly critical and cautious and understanding of what these types of studies in general mean, and also the fact that we've tried to kind of get at this baseline risk where we can report these proportions in both prescribed and non prescribed pregnancies should really allow for easy access to what these results mean. Rather than kind of speaking generally about relative increases, we can speak objectively about proportions in these data in these patients.

Speaker A

00:08:35.130 - 00:09:09.040

Yeah, and absolutely, as you mentioned, it's part of the picture in terms of the decision making process that doctors and women might want to take on in terms of information when informing their decisions. So I think this is really important work, as you say, looking at those absolute risks to help guide those conversations as well.

But I think that's probably a great place to wrap things up.

And I think it's been great to hear more about the research, and hopefully, as you mentioned, it's building up the evidence in this area and helping women and clinicians make those decisions together.

Speaker B

00:09:10.410 - 00:09:10.890

Thank you.

Speaker A

00:09:11.290 - 00:09:26.730

And thank you all very much for your time here and listening to this BJTP podcast.

Flo's original research article can be found on bjgp.org and the show notes and podcast audio can be found@bjgplife.com thanks again for listening and bye.

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?

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.

Yeah, fair enough.

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.

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.

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.

Specifically at the risk of miscarriage here.

What did you find?

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.

And it's important to not kind of trivialize that increase in risk.

But I think it's also incredibly reassuring that when we kind of really place it within what the underlying risk is had someone not taken antidepressants, it's very, very small.

Yeah.

Yeah.

I think this is a really important piece of the puzzle for risk communication.

Being able to show relative increases in risk, which are incredibly useful alongside what that actually means in terms of the percentage, the proportion of people that experience an outcome, because it just reminds people that, you know, clinicians and patients alike, that this isn't something that you have complete control over.

This isn't purely your behavior driven.

It's not.

So I think that can be really kind of reassuring for Individuals who feel that kind of burden of risk mitigation.

We see it in Heather James's paper in BJDP last year, a beautiful qualitative study speaking to women who had experienced antidepressant use during pregnancy and talking through their decision making process and their fears and concerns.

And a couple of the participants who were involved in that study cited miscarriage as one of a specific, one of their specific concerns when taking antidepressants during pregnancy and actually discontinued their antidepressants because they were worried about miscarriage.

So these concerns are having direct impacts on individuals and their behaviour and, you know, their potential management of their depression and anxiety.

So, yeah, I think it's important to balance these risks against the mental health risks for the woman who's taking or needing antidepressants.

And I think, as you point out, that was demonstrated beautifully in that qualitative research as well.

Definitely.

I wanted to sort of just draw back to how we can use these results in practice, really.

And I wonder what your thoughts are about how clinicians and women should use these findings to inform their decisions around using antidepressants in pregnancy.

Absolutely, yeah.

So while I'm hoping that these results, as a non clinician myself, I'm hoping that these results can be informative for decision making.

This isn't the only piece of evidence out there and it shouldn't be considered as the kind of gold standard, because it isn't.

We utilize a lot of methods and comparators, we use large data, we've thought carefully about all of the things that might be driving these effects and discuss them at length.

But it's not the only piece of the puzzle.

I'm hoping that these results can help to kind of illuminate what the truth might be and the factors that might be influencing our perception of the results.

So understanding data, understanding methods that will make us kind of rightly critical and cautious and understanding of what these types of studies in general mean, and also the fact that we've tried to kind of get at this baseline risk where we can report these proportions in both prescribed and non prescribed pregnancies should really allow for easy access to what these results mean.

Rather than kind of speaking generally about relative increases, we can speak objectively about proportions in these data in these patients.

Yeah, and absolutely, as you mentioned, it's part of the picture in terms of the decision making process that doctors and women might want to take on in terms of information when informing their decisions.

So I think this is really important work, as you say, looking at those absolute risks to help guide those conversations as well.

But I think that's probably a great place to wrap things up.

And I think it's been great to hear more about the research, and hopefully, as you mentioned, it's building up the evidence in this area and helping women and clinicians make those decisions together.

Thank you.

And thank you all very much for your time here and listening to this BJTP podcast.

Flo's original research article can be found on bjgp.org and the show notes and podcast audio can be found@bjgplife.com thanks again for listening and bye.