Antidepressants, Pregnancy, and Autism: Really Time to Worry

Adam Urato, MD
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The full article “Antidepressants, Pregnancy, and Autism: Time to Worry?”  was originally run on Mad In America on January 16, 2014.  This Update has been added given the recent new research on antidepressants, pregnancy, and autism.

On Monday April 14th, an important new study from Harrington et al was published in the journal Pediatrics (the official journal of the American Academy of Pediatrics.)  The study was designed to examine prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the risk of autism spectrum disorders (ASDs) and other developmental delays (DDs).  Nine hundred sixty-six mother child pairs were studied and the researchers found that in boys, the association between maternal SSRI use in the first trimester and autism was very strong (OR 3.22).  The association between third-trimester maternal SSRI use and developmental delay was even stronger, with an odds ratio of 4.98.

A few very important points stand out about this study.  We know from animal studies that SSRI exposure during development appears to affect males more than females.  This was elegantly demonstrated by Darling in 2011, Zhang in 2013, and others.  So it would make sense in human studies to analyze the effects on boys and girls separately.  Unfortunately, none of the human studies has done this—until now.  Rebecca Harrington, Li-Ching Lee, Irva Hertz-Picciotto, and their research group should be applauded for realizing the importance of studying the effects of SSRI exposure in boys and girls separately.  And what they found was deeply concerning.  Just as the animal studies have suggested, the effect of exposure on the boys was dramatic.  It was the boys who had the significantly elevated rates of autism spectrum disorders and developmental delay.

The second point that must be made about this study is that the magnitude of the effect is very high.  In scientific research we are used to seeing odds ratios like 1.5.  An odds ratio of 1.5 would represent a 50% increase in risk.  An odds ratio of 2 represents a doubling of risk.  But what this current study from Harrington is showing us are odds ratios of 3.22 for autism and 4.98 for developmental delay.  This represents more than a tripling and almost a quintupling of risk for these problems with SSRI exposure in pregnancy.

The third point about this study and the other studies showing a link between antidepressant use in pregnancy and autism is that this appears to be an effect from the antidepressants themselves and not the underlying depression.  Many readers are confused by the fact that the authors of these studies often state that “association does not prove causation,” that they haven’t proven that the antidepressants caused the autism, and that they cannot entirely rule out other factors.  This is correct.  These studies are not randomized controlled trials but rather observational studies, so the authors will always point out these limitations until a randomized controlled trial is done (which is likely not going to happen anytime soon.)  But this study, and many of these studies, have made every effort to account for underlying depression and they show that it is the antidepressants and not the depression that is associated with the complications.  Most importantly, these studies are showing similar effects to what we see in the animal studies.  The pregnant animals being exposed experimentally to SSRIs are not depressed, but their offspring are showing neurobehavioral changes (that resemble autism) and evidence of brain injury.  We now are seeing similar findings in the human studies.  So to blame these findings on the underlying depression just doesn’t make sense.  From the basic science data, to the animal and human studies, this appears to be a basic example of a chemical injury to the developing brain.

The fourth point that should be made is that we now have more than enough information to warn the public on this topic.  Exposure to SSRI antidepressants during pregnancy can negatively affect the developing brain and cause dysfunction.  This is clear from the animal data and is also seen in the human studies.  Women of childbearing age, healthcare providers, and the public need to have this information.  The FDA needs to update its labeling on these medications and issue a warning.  The CDC needs to also alert the public to this data.  We have been down this road before with drugs in pregnancy.  Diethylstilbestrol (DES) was used in pregnancy for 33 years (1938-1971) before the FDA issued a warning.  We have now been using SSRIs in pregnancy for 27 years and the scientific data has now progressed to the point where there is clear evidence of harm and the public should be warned.

The final point is that none of the above discussion means that we should ignore depressed pregnant women.  Depressed pregnant women need good treatment and care.  But the key issue is how to treat them.  The evidence is increasing that non-drug approaches to depression, such as psychotherapy and exercise provide results that are as good, or better, than drugs for many patients with depression.  At the same time, the evidence is increasing that these drugs lead to pregnancy complications like miscarriage, birth defects, preterm birth, newborn complications, and long-term developmental problems like autism and lower language ability .  Given this scientific evidence, the common sense approach to depression in pregnancy (and for women of childbearing age) is to emphasize and prioritize non-drug approaches.  These non-drug approaches have been shown to work for many patients and they are not associated with complications such as autism spectrum disorder and developmental delay.

Please go to the original post from January 16, 2014, “Antidepressants, Pregnancy, and Autism: Time to Worry?” for more details.

15 COMMENTS

  1. Seriously , anti depressants for pregnant women ?

    Real FN smart people , lets expose the unborn to serotonin re uptake inhibitors , ya that makes sense. Alot of FN sense

    Let me guess , the mothers are “at risk” for suicide or some crap like that, that got to be it right. To bad there is no evidence there pills ever prevent suicide. Only cause it.

    I can only Imagine pharmas internal memos on SSRIs and pregnant women, “torture” the data , our profits , our profits !!!

    ” I appreciate your help with this and second your suggestion that any additional resources will be a small price to pay for the molecule.”

    http://web.archive.org/web/20120122013020/http://www.furiousseasons.com/zyprexa%20documents/ZY100378062.pdf

  2. Thank you for updating your article. My adult child has both learning disabilities and was diagnosed with autism at a young age. I took another type of medication, but now believe that not only SSRIs, but also many other drugs routinely given to pregnant women probably also cause autism and learning disabilities. As many other readers have commented on this site, where is the FDA and science and medicine on this huge concern? The silence is very telling. There is frankly a lot of money at stake for pharmaceutical companies. Profit comes before people in our current economy and government.

    • Thank you michellerudy for your interest in my post. I addressed the concerns about case-control studies in the fourth paragraph of this post (my third point on this study.) You are correct that case-control studies have limitations and the website you link to makes some relevant points. The Harrington study (http://pediatrics.aappublications.org/content/early/2014/04/09/peds.2013-3406) is not a randomized-controlled trial, so the authors are clear to point out that it does not prove causation. But it does show a clear association between SSRI use in pregnancy and autism (and developmental delay) in the boys. Could this possibly be due to some other factor in the SSRI-using mothers? Yes, that’s possible. But I don’t think it’s probable because what is deeply concerning is that the animal studies (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215047/) show that when small mammals (e.g. rats and mice) are exposed to SSRIs during development, these animals develop neurobehavioral changes that resemble autism. Then when we study this question in human populations we are also finding that the children exposed to SSRIs during development have increased rates of autism (even after controlling for underlying depression and other possible confounding factors.) So to blame this effect on the underlying depression strikes me as somewhat farfetched—the results in the human studies echo what we are seeing in the animal studies of SSRI exposure.

      To use another example, in animal studies, pregnancies exposed to SSRIs have increased rates of premature birth (http://www.ncbi.nlm.nih.gov/pubmed/17652957). When we study this association (i.e. between SSRIs and premature birth) in humans we also find increased rates of preterm birth in the SSRI-exposed pregnancies. (Numerous studies have shown this, most recently Huybrechts, et al 2014 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966829/). This association persists even after accounting for underlying depression and other possible confounding factors. So it just doesn’t seem to make sense to blame the preterm birth (or the autism) on other factors in the human studies when we see the same complications in the animal studies with SSRI exposure.

  3. Psychiatry is a profession without a field in which to operate. It is a phantom profession. It is based on the assumption that if I have a condition which someone decides at some point in history is schizophrenia, then the obvious treatment will be gotten from a doctor, an MD, who has specialized in a fantastic area called psychiatry. With a nice glossary of technical and atrocious sounding terms some of which will be applied to me plus a certain studious, professional, scrutinizing look this man or woman will make certain unintelligible pronouncements which are really gibberish; and I might recover after some time or not. The addition of concoctions less likely to help than to harm will be administered and perhaps my blood will be examined at a later date to see if the dose is toxic. All this is expensive as well. The end product for the psychiatrist for this imaginary activity is a nice house, perhaps an expensive European car, and a fairly high status among the ignorant who are legion.

    Whether he succeeds in driving out my devils will not matter as the way this racket is arranged he has succeeded even if he fails. And he fails and fails and fails. In a sense we should pity this man who does so much harm with his strange profession. He is really a failed wizard. He never attended wizard school. Poor deluded man or woman.

  4. In a society that has debated whether women who use cocaine during pregnancy should be incarcerated, I think it is absolutely ludicrous that we don’t question bathing a fetus in drugs that alter brain chemistry in direct and extremely powerful ways–ways that the mammalian nervous system has never been exposed to before in evolution and has no way to adapt to–during the months that its brain is most vulnerable to injury. Altering the chemistry in the synapses in a brain that is actually just forming, growing, from nothing–how does that make sense?

    I cannot understand how anyone who managed to graduate from medical school could possibly think this makes sense or is okay. I know the pharmaceutical companies are sociopathically greedy and without conscience, I don’t expect logic or restraint or ethical behavior from them any more, but these prescriptions are written by actual physicians. What is the disconnect in logic here? How can they possibly think that this level of risk to a fetus makes any sense at all?

  5. In scientific research we are used to seeing odds ratios like 1.5. An odds ratio of 1.5 would represent a 50% increase in risk. An odds ratio of 2 represents a doubling of risk

    Don’t think so. Actually an OR of 2 would be the 50% increase, not a doubling.

    Let’s say the probability of A is 50% and the probability of B 33%. Then the odds ratio of A to B is 2 ([1:1] / [1:2]).

    But A is twice as likely. A is only 1.5 times more likely than B (33% * 1.5 = 50%).

    • Well, I was also wrong to imply OR=2 always equates to “1.5 times more likely”. In fact, it depends on the absolute probabilities. Only if A and B both have very small probability is OR=2 is (approximately) a doubling of risk.

      E.g. if A occurs at a rate of 2%, and B at 1%, then the chance of of A occurring is exactly double that of B. The OR of A to B is (2:98)/(1:99)=2.02.

      This brings up a different point: Lay people like me, who want to make make informed choices, are probably more interested in the absolutely probabilities. I mean, I could buy 1 lottery ticket vs 100 lottery tickets–the OR would be a hair above 100, but am I going to win the lottery either way? Nope.

      When the chance of a birth defect goes from 5% to 10% thats a big deal, compared to say .1% to .2%, even though both cases are doubling.