Chemicals Have Consequences—Antidepressants and Pregnancy: An Interview With Adam Urato, MD

On our podcast this week, we hear from Dr. Adam Urato.

Adam graduated from Harvard Medical School in 1997 and has been practicing medicine for over 25 years, specializing in obstetrics and gynecology. He cares for pregnant women on a daily basis as an attending maternal-fetal medicine physician at MetroWest Medical Center in Framingham, Massachusetts. He writes and lectures regularly on antidepressant use during pregnancy.

Adam has contributed to Mad in America’s continuing education efforts and his free course “Antidepressants and Pregnancy” can be found on Mad in America’s education section. It is an informative and comprehensive look into a little-discussed but very important area of women’s health.

For this interview, Adam joined me to discuss what we do and don’t know about the effects of antidepressants on babies and mothers and also the importance of counselling in order to aid families in making important decisions about pharmaceutical drug use.

The transcript below has been edited for length and clarity. Listen to the audio of the interview here.

James Moore: Adam, welcome. Thank you so much for joining me today for the Mad in America podcast. We’ve had a lot of interest in hearing from someone with your particular skills and abilities. So, thank you for joining us.

Adam Urato: It’s a real pleasure to be here, thanks for having me.

Moore: You are a specialist in obstetrics and gynecology and you’ve been practicing medicine for over 20 years now. But in addition, I think it’s fair to say that you have developed a critical view of the way that some prescription drugs are used for pregnant women.

So to get us underway, could tell us a little bit about you and what was it that led you to question some of the conventional wisdom in this area?

Urato: I went into obstetrics because when I came to medical school, it was a cool thing and I loved doing it. I am very grateful that I’m able to do this every day. It’s a very diverse field as far as what we’re doing on a day-to-day basis. We’re taking care of pregnancy and pregnant women, but we end up dealing with medical issues and surgical issues. I still deliver babies and do operations, C-sections, and vaginal deliveries.

I’m also a full-time clinician and I take care of patients all day. I take care of patients at the hospital where I was born, which is a real pleasure for me. It’s great to be active in my home community where I was born and raised. I think the other element to it honestly, is that it’s a miracle, the developing baby and life and I know that sounds a little bit corny, but it really is.

As far as my interest goes in medications, this is something that I began to get interested in medical school when I was seeing how many medications our patients were on. I remember when I did my internal medicine rotation, my chief resident told me when they come in to make a list of all their medications and it would typically be anywhere between 10 and 20 medications.

I remember thinking at the time, what are the interactions between all of these medications that we’re using? Then when I did my residency in obstetrics and gynecology, I remember hearing discussions about drug safety in pregnancy and it got me thinking.

One of the overarching approaches that I try to emphasize to people is that medications for the most part are synthetic chemical compounds. And I really try to get people to think about that and understand that because I think that the pharmaceutical industry has done a great job at portraying them in their commercials that we have over here as blue skies and trees and beaches and rainbows and all of these sorts of things that distract you and take your eye off the ball a little bit.

At the end of the day, medications are synthetic chemical compounds, they are coming out of a chemical factory and they have chemical effects, that’s what chemicals do. So even as a medical student I was looking at the lists of medications and thinking about the developing fetus and chemical exposure.

Moore: In the introduction to this interview I mentioned the MIA Continuing Education course you did and the phrase you used in that was “chemicals have consequences.” That really stuck with me. It’s such a useful phrase to have in mind when we’re sold some medications almost as if they are kind of a lifestyle accessory. But, as you say, they are chemical compounds that have many effects on the body.

Urato: You just made my day by using that phrase because it’s one that I use commonly and I think my sons would say, “Oh, my God, there’s Dad using that phrase again.” But that is something that I think is important to get across to people, chemicals have consequences. Chemical compounds have chemical effects on biologic systems, that’s what they do. And also for us to always keep that in mind that it doesn’t mean you can’t use a medication. But it means that whenever you are taking it, you need to keep in mind that it is a chemical and then consider is the benefit I’m going to get from this going to offset these chemical effects.

I encourage people to embrace this. If you’re going to take a medication or thinking about taking a medication, it’s worth looking up the chemical structure on Google, you’ll see the rings of the carbon atoms, the nitrogens or whatnot, and understand that this is a synthetic chemical compound that you are about to ingest. And that it’s going to go into not just the location of what you’re trying to address, like if you have a headache to your head, or if your knee hurts to your knee. It’s typically going all over your body throughout all of your cells and going to have a consequence. It is going to have a chemical impact.

Moore: Thank you. So perhaps we can discuss some of those effects a little bit. People listening will know that serotonin is often talked about as being important in the treatment of depression, which I think it’s fair to say in itself is questionable. But it turns out that serotonin is pretty crucial in fetal development. So, I wondered if you could share with us a little bit about this and then why we should be concerned about the effects of selective serotonin reuptake inhibitors (SSRIs) on the mother’s body as well.

Urato: Sure. Before I go on, I do just want to jump in and make one point clear. I think a lot of times people hear these questions and they hear the answers and what they are hearing is, “This means that a pregnant woman should not be maintained on the medication.” I just wanted to make clear that that’s a separate question and something that I hope we can get into later. Women who are suffering from depression during pregnancy or other mental health issues need compassion, they need good care, and they shouldn’t be ignored or left to suffer.

I do this every day in my office and I work in the community where I grew up, so these are my neighbors and I take really good care of them. If they come to me and they’ve got a mental health issue, if they’re on an antidepressant or another psychotropic medication, you don’t make them feel guilty. You don’t embarrass them, you treat them with kindness, sympathy, and with dignity. You work with them to come up with the best plan for how to manage their mental health during pregnancy. I always tell them that’s the goal, we don’t tell them, “Look, you are pregnant, so you just need to suffer and do poorly.” That’s not the way to treat a pregnant woman.

So I want to just put that out there and be clear because I think people sometimes mistake a discussion about the chemical effects of antidepressants on the developing fetus with a discussion about how pregnant women on medication should be managed. And I just want to be clear that those are two separate things.

With that being said, I think that your question is a good one about fetal effects. As you were saying, there’s been a lot of recent controversy about that whole model of there being a serotonin deficiency and Joanna Moncrieff’s paper that came out got a lot of attention this past few months ago.

Serotonin is a crucial cell signaling molecule. It’s a neurotransmitter and it modulates developmental processes like cell proliferation and cell migration. When it comes to the wiring of the brain, it acts as a chemical messenger. So the serotonin system is crucially important early in the development of the embryo and it goes on from there throughout development.

This then gets back to what we were just discussing, which is that if you take a chemical and you alter the normal function of that serotonin system, it will have consequences and you’d expect to have possible complications. And we do see that the studies on antidepressant use in pregnancy are numerous and challenging for a variety of reasons.

There is no randomized controlled trial for antidepressant use in pregnancy, it’s not considered to be ethical to take a group of women and randomize half of them to the drug and the other half to other treatments. But that being said, we still have a lot of accumulated data over the years to help us be able to look at these things.

Right now, my reading of the literature is that there are links to miscarriage, birth defects, preterm birth, and also a condition called preeclampsia, which is a well-known complication in pregnancy where the mom gets high blood pressure and typically shows protein in her urine at the end of pregnancy. Also, women who are on SSRI antidepressants are at higher risk of postpartum hemorrhage. In the UK there’s a warning that they put out recently about this.

Then from there, there are newborn behavioral issues or newborn behavioral syndrome, which is a constellation of problems or issues for the baby including agitation, restlessness, irritability, poor feeding, trouble sleeping, low blood sugar, hypoglycemia, trouble with warmth, regulation, hypothermia, respiratory distress, hyperreflexia, tremors, seizures. These things can go into this newborn behavioral syndrome, which is more common with antidepressant exposure in pregnancy.

This all kind of hangs together, I think with the chemical exposure to a developing fetus, and to the mom.

Moore: SSRIs are made such that they can cross the blood-brain barrier to get to the site of supposed activation, does that also mean that they can cross the placenta? Do we know that?

Urato: Absolutely. It’s a great question. I was discussing with that assumption but that’s an important point to make. They do cross the placenta. Studies have been done where we check the baby’s cord blood, we can sample and you can find levels of the antidepressant in the fetus. They are crossing over into the fetus during pregnancy and throughout development.

Moore: When you talk about the evidence supporting the risk of harm to the fetus from SSRIs, you are quoting papers in the big medical journals. So this isn’t fringe science, is it? This is well-established evidence that’s sitting in some of the biggest medical journals.

Urato: That’s exactly right. In fact, just recently, the CDC group on this put out data which showed a link to birth defects with the antidepressants, in particular venlafaxine, but also the SSRIs, as well. Venlafaxine (Effexor) is an SNRI. This is published in a big, mainstream journal and it is also on the CDC’s website for that matter. If you look up birth defects with the use of antidepressants, you will find that the CDC does highlight that study that did show the link.

Moore: You were talking about some of the behavioral issues that might affect babies that have been exposed before birth. I understand that the children born of mothers who were on antidepressants can experience neonatal withdrawal syndrome. I wondered if you had come across that, what might be the effects on the baby and how can it be managed?

Urato: If you think about these drugs, we know that they can affect serotonin signaling, they are “selective serotonin reuptake inhibitors.”

We can say scientifically that we know they affect the serotonin system and we know the serotonin system is crucial for the developing fetal brain. So if you put those two parts of the equation together, then you can conclude that there’s going to be an impact on the developing fetal brain from a fetus being exposed to an SSRI or other antidepressant throughout the development of the brain.

We see that right off the bat with the newborn behavioral syndrome. People also call it newborn withdrawal syndrome, but it’s believed to not be just withdrawal and the reason for that is we see some of these things right from the get-go. The other thing that points to that is that there’s a very interesting study that was done back in 2011. The lead author was Eduard Mulder, and he did a study where he looked at women who he knew were users of SSRIs and followed them using ultrasound of the fetuses. He compared them to depressed women not on medication and also to normal controls.

That group was able to demonstrate changes in ultrasound parameters, particularly with the behavior of the fetuses throughout pregnancy. For example, in the third trimester, the fetus exposed to the antidepressants was getting less non-REM sleep and they were more active.

So we can see some of these effects even in utero, which again, to me makes sense, you’re putting a chemical into the fetal brain that can affect the serotonin system. Serotonin plays a crucial role in the development of that brain and cell signaling. So if you’re doing that, you’d expect that you might see effects. We do see some of those effects in utero and then after birth, we see these effects.

Looking longer term, it gets harder to study and those studies are mixed, but there certainly is a signal for things like autism, ADHD, language processing, and motor function. Also, there’s been a recent paper, looking at gastrointestinal complaints, which, again, would make sense because of serotonin’s important role in the gastrointestinal system, both in the developing fetus as well as in adults.

I think that it hangs together scientifically that if you’re using this chemical that affects serotonin and if serotonin does play a critical role in fetal development, then there are likely to be complications and concerns with that.

Moore: Thank you, Adam, you make such an important point about the delicate balance needed to help people understand what the risks might be and to help them make the best choice for them and their child and family.

You’re a clinician, so when you are counseling a woman or a couple who might be thinking of having children, what do you tell them? How do you balance the need to give them informed consent, bearing in mind that they might not have had the information they needed when they first started on SSRIs?

Urato: So this is a really important point that I’d like to make. I think that this message and this counseling need to go out to women of childbearing age as opposed to trying to address it once the woman is pregnant. Maybe the major reason for that is that these drugs as we’re realizing more and more are very difficult to get off for many patients.

Typically, it’s hard to throw withdrawal into the mix with a patient who is newly pregnant and undergoing all of the challenges of the first trimester with things like nausea and vomiting, exhaustion, and the sort of changes in your life that occur when you get pregnant. So it becomes a very difficult conversation to try to sort through at the time of pregnancy at that first visit in that first trimester. This is a message that needs to go out to women of childbearing age and physicians who take care of women of childbearing age. I think you could argue it’s a message that should go out to everybody; what are the risks and potential benefits, what are the alternatives and so on.

I think that when they’re pregnant, I tell them that we don’t want them to suffer and I treat them with compassion, you don’t make them feel guilty for being on something and you try to individualize it. A lot of people look for the one size fits all answer, should women be on them or should women be off them? What’s the one size fits all answer? It doesn’t work that way.

If a woman is on a medication that she’s stable on, she’s doing well on it and she feels that if she comes off she’ll do poorly, she will be suffering, she won’t be functional, then that is something that has to be taken into consideration with the counseling as well as with her desire to stay on the medication. I have a lot of patients who do stay on the medication during their pregnancy and when they make that decision, I support them and I take good care of them.

The time that the drug is started, though, is where I think there needs to be this effort to let patients in general and in particular, women of childbearing age know the risks of the medication including the difficulty coming off of them. You may end up pregnant on this medication and with these issues of fetal exposure and potential pregnancy complications and fetal complications. I think that needs to be weighed more into the calculus than perhaps it is.

Moore: I read recently that antidepressant and antipsychotic use in pregnancy has doubled in the last decade. Should we be concerned about that? Should we be trying to ensure that informed consent for maternal-age women is somehow strengthened?

Urato: I look at this again through a lens of chemical exposure and just step back from it. If you’re asking the question that we’ve got a doubling of chemical exposure to pregnant moms and their developing babies, is that concerning? Absolutely. I think it’s important to take mental health seriously. I think it’s also important, as I was saying before to provide good care. But I think that, given the science, it looks like the longer-term outcomes are not the rosy picture that was originally painted of these medications when they came out.

Moore: We talked a little while ago about evidence of exposure harm being in the big, mainstream medical journals. So, with this knowledge within the medical community, I wondered what the response of the regulator, the U.S. Food and Drug Administration (FDA) has been to these issues.

Urato: It’s been woefully inadequate. I think that we are not doing a good job with drug regulation in our society and probably around the world. We’re dropping the ball on informing the public about medications and their effects.

We may get into talking about Makena. Makena is a drug that we have used in pregnancy for about the last 20 years in the United States. It’s a synthetic hormone that was being injected into women to prevent preterm birth. It was FDA approved in 2011. It was being used even before then, but subsequent evidence has shown that it doesn’t work, it doesn’t appear to actually stop preterm birth, and there are risks associated with it.

When you step back and you look at that, you say, “We’ve been injecting pregnant women with a synthetic hormone that doesn’t work for the last 20 years.” Something has failed there and I think it’s been a failure of drug regulation. I think we need better warnings for the public.

If you look, for example, at the labeling on the SSRIs or Prozac, there is a medication guide at the end of the label, but I think most patients and probably most providers aren’t looking at that and aren’t addressing all of those issues. I would recommend anybody listening to this podcast to read through that medication guide. The FDA is highlighting many of the problems with these medications but it doesn’t seem to be getting out to the public as well as it should so that people are more aware of these things.

Moore: I am one of those sad individuals that has read through the leaflet of the drugs that I had and there’s a section under the list of adverse events where it says “incidence unknown.” Of course, you could read that and think, “Oh, well, because it’s not known, it must be so rare that it is not worth capturing.” But actually, I believe that “incidence unknown” means it could be a major problem, but there’s just not enough research to prove an effect one way or the other.

Urato: I think that’s a great point. The “incidence unknown” shouldn’t be reassuring; it could be quite concerning that that’s there. I wanted to just highlight that in the medication guide, one of the things that they say before starting Prozac is, “Tell your healthcare provider if you are pregnant, or plan to become pregnant; it is not known if Prozac will harm your unborn baby.” That’s the unknown that you’re getting at there and that’s what patients always ask in the office. That’s what they want to know before they’re taking a drug or are exposed to anything.

Pregnant women will typically ask, “Can this hurt my baby? Can this affect my baby?” Pregnant women are smart about these things as far as trying to minimize exposure to things that could harm their baby. So I think that we need to do a better job at getting information out there that there is scientific evidence of harm and that needs to be put into the calculation for moms and families when deciding about these things.

Moore: You remind me, Adam, that here in the U.K. we did have a terrible experience in the late 1950s with the drug thalidomide. Interestingly, although our regulator (MHRA) didn’t block it, it was blocked by the FDA in the U.S. The fallout of that was just horrific and we must avoid any situation like that with a drug that causes such terrible problems for babies and mothers.

Urato: It’s very sad. As you said, the FDA was able to block that drug, but subsequently we’ve seen that they aren’t doing as good a job, and certainly not with Makena.

I talk about Makena a lot because it’s active right now but it was initially approved based on one very flawed trial from 2003. There were a lot of problems with that initial study but the drug was given accelerated approval in 2011. With accelerated approval, the idea is to get drugs onto the market that meet a significant need and preterm birth was a significant need. So they got it based on that one flawed study, but the idea was that the company would be required to do a confirmatory trial in short order to be able to demonstrate a benefit. But it didn’t happen quickly. This went on for years, where we kept giving pregnant women this drug until finally in 2019, eight years after the initial approval, finally, the second study results became available and showed that the drug didn’t work.

In the meantime, thousands and thousands of women had been exposed and the company had made billions of dollars off the drug, but what’s really disappointing is that even after 2019 the drug still hasn’t been pulled off the market. The FDA has called for it; there have been a few meetings. People think that it’s imminent that this is going to occur. But we’re almost four years after the drug was shown not to work and the confirmatory trials failed and it still hasn’t been pulled off the market. There are still women that can be injected with this ineffective synthetic hormone that carries risks.

Moore: I could be wrong about this but wasn’t there some issue about it being preferentially used for black women over white mothers, was that true?

Urato: I’d see that as just corporate or big pharma spin at its worst. The confirmatory trial failed, so they were trying to salvage it by saying that “Well, the first trial was done with a lot of black women in that trial and the second one was done with few black women. So we can look at this as a drug that helps black women and we shouldn’t take a drug off the market that helps black women.” They were basically using a racial equity argument, which I thought was misleading and unethical. The FDA had looked at both studies based on race and had not found that it made any difference.

In fact, the initial trial from 2003 did not show a selective benefit in black women. That was being done I think as a way of trying to salvage the drug or keep it on the market by using a misleading argument. Fortunately, it looks like the FDA didn’t buy it and we’re hoping that the withdrawal of the drug is going to be imminent. Although I’ve been feeling that way for the last four years. Hopefully, this is going to be coming in the pipeline soon.

I did just want to make a comment going back to something you had said in particular about pregnancy. Pregnancy is a time when there’s a lot of development and a lot of rapid change. So when you’ve got a rapidly changing or rapidly developing biologic system, it’s particularly sensitive to these chemical exposures that I’m talking about. So I think that’s why in particular, we’re so concerned with pregnancy for the developing baby, we can see harms because we’ve got a rapidly developing biological system that we’re then putting a chemical exposure into and I think that that leads to the possibility of more harm.

It’s interesting because another area where we see a rapidly developing biological system is sperm formation for males. When studies have been done looking at SSRI use in semen analysis, we see an effect. We see DNA fragmentation and we see lower concentrations and so that’s another example of a sort of rapidly developing process. Sperm are being subjected to chemical exposure and we’re seeing results from that.

Moore: It’s so important to have these discussions because if these papers are in medical journals that’s great, but for the average person in the street, they have little to no chance of actually getting the information they need to make some fundamentally important decisions for themselves and their families.

Urato: Trying to get the information for patients is a big problem and I think that part of that honestly speaks to the power of the pharmaceutical industry. Our system of regulation, as well as our system of informing the public has become rigged. And it’s being rigged by corporate and big pharma cash.

In an ideal world, you would have drug companies trying to come up with drugs and then you would have an aggressive academic community: universities, your experts, your specialists, who would really go over the data with a skeptical eye and would try to probe and ask: “Does this stuff work, is this going to be good for the public?”

So my vision of how this should be working would be your academic medical centers holding pharma’s feet to the fire. Looking carefully at these drugs, investigating and standing up for the public. And the FDA would function the same way. They would stand firm and strong for the public.

But what’s happened is that the FDA is funded by the pharmaceutical industry and many of the FDA folks leave the FDA to go work for pharma. It’s a revolving door and the same thing is true in academic medicine. Many of your leading universities are funded by pharma and the researchers are funded by pharma. So you end up with the pharmaceutical industry, basically creating what I would call a corporate conventional wisdom around drugs. Whether it’s Makena for preterm birth or antidepressants, the pharmaceutical industry creates that corporate conventional wisdom.

Typically, they roll it out with a story and with a spin. You’ve got a serotonin imbalance, we give you this drug and it corrects the imbalance and makes your life better and everyone’s life better. They roll that out and then they’re assisted in that rollout. Nobody would believe it if it were just the pharmaceutical company saying this. But when you’ve got your leading academic medical centers saying this, when you’ve got your experts saying this, and when you’ve got the FDA approving these things, it creates this conventional wisdom and this information for the public that’s going to lead to increased sales. And that’s the whole point of it.

The reason why the pharmaceutical industry is showering cash on academic medicine and showering cash on the FDA and the reason it works this way is that it ultimately leads to increased corporate profit through increased drug sales, which is what they’re aiming for.

That doesn’t work best for the public. So we need to get back to where the medical establishment, that would be the physicians, academic medical centers, the researchers, the FDA, the CDC, where these folks are all working on behalf of the public, rather than on behalf of big pharma and the device makers.

Moore: Do you think there’s a chance of that change happening? There’s so much money generated in sales that the pharmaceutical industry can buy power and influence. I think it’s one of the largest lobby groups in Washington.

Urato: I think that solving this is challenging. Getting independent voices out there like this is important. And I think having a wary, skeptical public does help with this. And at least from what I’m seeing, just in general and also in my office, I think the public has become informed and is skeptical and wary. I think that they feel like “Oh, all these people are being paid by the pharmaceutical industry” and it creates a lot of skepticism. I think you’re seeing that that’s becoming more prevalent in society where people just aren’t buying these recommendations.

You can have a recommendation from the FDA, the CDC, or the leading medical societies that you need to take drug X, Y, or Z or whatnot. The public will often say, “No, we’re not going to do that.” And I think we’re starting to see this disconnect between these official recommendations and what the public is thinking.

You can only play the game where you’re paying the regulators, you’re paying the researchers to get the result you want, for so long before people realize it’s a rigged system. I think that there are a lot of people that are becoming more and more aware of that, and are looking for unbiased voices in this and trying to drill down and figure out what the actual accurate information is.

Moore: Is there anything else that we hadn’t touched on that you thought it important to share?

Urato: I think probably the biggest thing is this issue of separate questions. The discussion of what an antidepressant is doing to a developing fetus is an important one. And it’s a scientific one and it has to do with chemical exposures and embryonic and fetal development. But that is a different question than whether a given individual mom in my office or any office should or should not stay on her medication during pregnancy.

Pregnant women with mental health issues deserve compassionate treatment and good care and shouldn’t be made to feel guilty or ignored. And the counseling needs to be thorough and comprehensive and supportive. So my concerns about fetal exposure are not meant to, in any way, disregard the importance of mental health or ignore a pregnant woman with mental health issues or not be sympathetic or compassionate to them. That being said, I do think it’s very important for accurate counseling for women to be able to get information about the effects of these drugs on developing babies.

The second thing I would say is important is the point that we’ve made several times, which is that chemicals have consequences. Don’t forget when you’re taking medication as a patient, when you think about medications, the drugs are synthetic chemical compounds, they are made in chemical manufacturing facilities and they’re going into your body, and they’re typically going to have widespread effects. So it’s important to keep that in mind.

I like to joke when I give lectures on this that in the food industry the orange juice makers, want to show in their ads the orange trees and it comes right off the tree, right? You don’t see that in the drug commercials. You get the people in the bathtub and the ocean and whatnot, but you’re not seeing the chemical manufacturing facility where everybody’s dressed in the white chemical suits and the goggles and shields making the chemicals that are ultimately going into your body into your brain and other organs. So it’s very important to keep that in mind as a patient as a citizen as a consumer these are chemical compounds and they have chemical effects.

Then I guess the last thing I’d want to emphasize is that this important talk needs to happen with women of childbearing age before pregnancy. We want to address these things not when they come in at 8 weeks or 12 weeks pregnant. You want to be addressing these things earlier and addressing it in general trying to inform the public about the risks, benefits and alternatives to antidepressants specifically, but also medications in general.

Moore: You’ve done a beautiful job of explaining the science for us and telling us how important it is to have a human approach to these issues when you’ve got someone in front of you who needs advice and who might have to take some difficult decisions. And I also can’t imagine it’s very easy to be a critical voice and to speak out on these issues given the resistance encountered, so thank you for all you do.

Urato: I appreciate the opportunity and being able to get the word out on it; thanks for giving me the opportunity.

 

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MIA Reports are supported, in part, by a grant from The Thomas Jobe Fund.