Doctor: Possible Links Between Antidepressants, Pregnancy And Autism

By Dr. Adam Urato
Guest Contributor

On Friday, a new study was released in the British Medical Journal showing that antidepressant use during pregnancy is associated with autism in the exposed children. This is now the second study within the last two years showing this link and it adds to the accumulating evidence of potential harm associated with the use of antidepressants during pregnancy.

Adam Urato, M.D., a maternal-fetal medicine specialist says evidence is growing on the harms of taking antidepressants during pregnancy.

Adam Urato, M.D., a maternal-fetal medicine specialist says evidence is growing on the potential harms of taking antidepressants during pregnancy.

The study was a case-control study from Sweden, which was fairly large: it looked at 4,429 cases of autism spectrum disorder and compared these cases to 43,277 matched controls. The researchers found that antidepressant use during pregnancy, with either SSRIs or nonselective monoamine reuptake inhibitors (another type of antidepressant) was associated with an increased rate of autism spectrum disorders in the offspring. The odds ratio was high at 3.34, which roughly means that antidepressant use was associated with more than a tripling of risk of autism in the children.

The study concludes:

In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.

These results do not surprise those of us who have been following the scientific studies in this area over the past two decades.

Serotonin: a crucial neurotransmitter

Serotonin, the first neurotransmitter expressed in the developing embryo, plays a crucial role in brain formation. Serotonin is essential for the growth and development of certain areas of the brain. It is involved in such basic processes as cell division, differentiation, migration and synaptogenesis. In short, proper functioning of the serotonin system is essential for the brain to form and function normally. The SSRIs and other such antidepressants are believed to exert their effects by blocking the reuptake of serotonin into neurons—the basic cell of the brain. For a developing baby, such blockade is occurring throughout the body (including the brain) and throughout pregnancy development. It is now well-established scientifically that autism is characterized by changes in the serotonin system. Hyperserotonemia is the most consistent neurochemical change in autism.

Animal Studies

Most of the data we have on developmental effects of the SSRIs on the brain comes from animal studies on small mammals (mice and rats). The majority of these studies show significant changes in the brains and behavior of exposed animals and these results are very concerning. The two best-known studies were published in the world’s leading scientific journals, Science (2004) and in the Proceedings of the National Academy of Sciences (PNAS) (2011). But these are just two examples of the many animal studies that show changes in the brain and behavior that result when the serotonin system is altered during development by the use of the SSRI antidepressants. In the Discussion section of these manuscripts, again and again, the authors warn us that their findings of harmful effects should make us concerned with using them in humans.

Human Studies

Several human studies looking at the effects of SSRI exposure during pregnancy have shown brain and behavioral changes in exposed children. In 2009, Pawluski, et al published a landmark study showing decreased S100B protein levels in babies who were exposed to SSRIs in utero—similar to alcohol and cocaine-exposed pregnancies. In 2010, Pedersen, et al demonstrated that SSRI-exposed children sat up and walked later and that they had behavioral changes. In 2011, Bellisima, et al showed that babies exposed to SSRI antidepressants in utero have dramatically higher levels of the brain damage marker Activin A in their blood and amniotic fluid. In 2013 Hanley, et al showed that SSRI-exposed children scored lower on gross motor and social-emotional testing. And these are just four of many studies that show changes in exposed children.

As far as autism goes, the first study came out in 2011. Croen, et al showed that SSRI exposure during pregnancy was associated with a doubling of the risk of autism. For first trimester SSRI exposure, the risk was almost quadrupled. Importantly, her study looked at depressed women not on SSRIs, and in this group there was no increased risk of autism. It was the antidepressant use that was linked to the autism and not the depression.

The current study by Rai, just published April 19th , also shows an increased rate of autism in antidepressant-exposed children and this does not appear to be a result of depression, but rather of the medication. Thus, the only two studies in humans that have asked the question: “Is antidepressant use during pregnancy associated with autism?” have found the answer to be a clear “Yes.”

Public Confusion

The authors of the recent study concluded that they cannot declare whether the problem is with the antidepressants or the depression. Many readers find this confusing. The reason the authors state this is that their study was not a randomized controlled trial (RCT). Only a randomized controlled trial (where half the depressed women are given an antidepressant and the other half a placebo) can most accurately assess causation. However, this type of trial has never been done with antidepressants during pregnancy and many people feel that such a trial would not be ethical.

However, an RCT is not always needed to presume that an agent is causing harm (for example, we have never had an RCT on cigarettes, but we have concluded that they cause harm) and an RCT is not needed to caution the public. In this case, we see clearly from the animal studies that exposure to SSRIs during development leads to changes in the brain and behavior –that often mimic the findings in autism. Then, in the only 2 human studies to look at this area, we see increased rates of autism in the antidepressant exposed groups (and not in the depressed/nonmedicated group.)

Balancing Risks and Benefits

SSRI antidepressant use during pregnancy is linked to pregnancy complications and risks for the baby, including what may be an increased risk of autism. These complications might be considered tolerable if there was solid evidence of benefit with the use of antidepressants by pregnant women. Sadly, in 25 years of study, not a single study has ever shown improvements in pregnancy outcomes in the antidepressant-treated group. In studies of nonpregnant populations, there is little evidence of clinically significant benefit with the use of antidepressants (when compared with placebo) by most patients with depression.

This second study showing an increased risk of autism in the children who were exposed to antidepressants during pregnancy is concerning. The current evidence that the SSRI antidepressants can injure the developing brain is clear and consistent. Pregnant women suffering from depression need treatment and care. But, with good evidence that non-drug therapies, such as psychotherapy and exercise, may provide at least as much benefit in the treatment of depression (if not more), it makes sense to first use these approaches in women of childbearing age—approaches that have not been linked to autism.

Adam C. Urato, MD is a maternal-fetal medicine physician at Tufts Medical Center, Assistant Professor of Obstetrics & Gynecology at Tufts University School of Medicine and Chairman, Department of Obstetrics & Gynecology, MetroWest Medical Center in Framingham. He has written previously on this topic here.

For another perspective, see this piece by a psychiatrist specializing in women’s mental health issues.

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  • Greg

    Vaccine Proponents Playbook, Argument Six: Everything
    Causes Autism Except Vaccines

    The anti-vaxers are so frustrating. They just don’t believe us when we tell them
    what really causes autism. Autism is caused by abused mothers, old mothers, fat mothers, stressed mothers, old fathers, old grandfathers, fathers in their 40s marry women in their 20s, engineer and tech parents, having siblings too close together, women not taking folic acid during pregnancy or having a fever or flu during pregnancy, or taking epilepsy drugs and anti-depressants during pregnancy (both new), lack of vitamin D, c-section deliveries, low birth weight, living too close to a highway, lots of
    rainfall, air pollution. Everything causes autism except vaccines!

  • Researcher

    Thank you Dr. Oz for sounding the alarm on antidepressants. There is a lot of research that most people don’t know about:
    1 in 6 become manic (bipolar) by taking antidepressants and will be wrongly diagnosed as suffering from bipolar disorder. They will then be told they need medication for life and given antipsychotics, lithium and antiepileptics (mood stabilizers) in cocktails that have never been researched.
    In the longest and largest antidepressant study conducted (STAR-D) only 3 percent had effect after one year of treatment with several antidepressants.
    7 out of 10 get their sex lives destroyed by these pills
    Suicide risk may increase with up to 600%, especially in young people.
    Once you have started on antidepressants you have an 85% risk of becoming chronically depressed. Without antidepressants, your risk for chronic depression is only 15%
    Antidepressants can both stimulate and numb feelings and thoughts so as to make people do strange and often violent things. Very honest and good people may suddenly steal, embezzle money and even commit murder.
    Many people have extreme side effects when they try to stop. They usually think it is depression and anxiety coming back, and don’t dare to try stopping again.
    Most doctors reduce medication too quickly when patients want to stop. You should never try to reduce more than 10% of the medication every 2 weeks. That means a minimum tapering period of 20 weeks. Rule of thumb: use one month to withdraw for every year you have been on the medication. 10 years of use=10 months tapering.
    In research, antidepressants don’t work better than sugar pills, even in the short run. So they are medications with extreme risks and no benefit.
    There are many treatments that work against depression. Simply taking a quick walk for 20 minutes 3 times a week has better effect in research than an antidepressant. Cognitive therapy works better than antidepressants, and have lasting effects.
    Google on Breggin and Whitaker to find more info and references to all of this research.
    Ex- National Institute of Mental Health researcher

  • http://www.facebook.com/vitopavlovivit Vito Alexander Pavlovic

    Every drug has an adverse effect of course, and I am sure that every drug given to pregnant woman during fetal development can have the same effect as antidepressants, so then why exclude a cumulative effect of vaccines on the Autism subject, you know its causing the most damage, come clean with this matter, the situation is only going to get worse, much worse!

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    To understand how autism is affecting children and families, look at the new book, The Thinking Moms’ Revolution.
    http://www.amazon.com/The-Thinking-Moms-Revolution-Inspiring/dp/B00BYB0KE0
    “The Thinking Moms’ Revolution (TMR) is a group of 23 moms (and one awesome dad) from Montana to Malaysia who all have children with developmental disabilities. Initially collaborating online about therapies, biomedical intervention, alternative medicine, special diets, and doctors on the cutting edge of treatment approaches to an array of chronic and developmental disabilities, such as autism, sensory processing disorders, food allergies, ADHD, asthma, and seizures, they’ve come together into something far more substantial.
    “Suspecting that some of the main causes may be overused medicines, vaccinations, environmental toxins, and processed foods, they began a mission to help reverse the effects. In the process, they became a tight-knit family dedicated to helping their kids shed their diagnoses.”
    Anne Dachel, Media editor: Age of Autism

    • lilady R.N.

      Could you possibly stay on topic (for a change), Ms. Dachel.

      Now you are Spamming the comments section and touting the new book from your affiliated TMR. You state that group first formed to discuss *certain therapies*. I have seen the therapies they promote; bleach enemas that they inflict on their autistic children, intrathecal stem cell transplants done at offshore unregulated clinics, IV chelation for “heavy metal toxicities” and chemical castrations inflicted by “doctors on the cutting edge of treatment” (Mark Geier whose medical license has been revoked) and do-it-yourself fecal transplants (by depositing parents’ own feces in pails left on the back porch).

      You and you ilk continue to support disgraced former doctors including the aforementioned Mark Geier and Andrew Wakefield…and their totally debunked *theories* about vaccines causing autism. Shameful.

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    One of the mothers included in the book, Thinking Moms’ Revolution, Alison MacNeil, was just on Fox
    News talking about the book: http://www.ageofautism.com/2013/04/alison-macneil-on-fox-friend-leading-the-thinking-moms-revolution.html
    One of the moms was also on Fox 5, Washington DC talking about the book.
    http://www.myfoxdc.com/video?clipId=8787473&autostart=true#axzz2QpO9NQpO
    I wrote this review of the book. http://www.ageofautism.com/2013/04/book-review-the-thinking-moms-revolution.html
    Anne Dachel, Age of Autism

    • lilady R.N.

      Still Spamming Anne…from your vast repository of off-topic comments?

      Get a grip and stop Spamming.

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    What does Dr. Urato think of all the vaccine-injured kids who were compensated for their autism?
    HDNet TV exposed the fact that while health officials continue to tell us studies show no link, the federal government has paid out millions of dollars for compensation for vaccine injuries that included autism.
    http://www.ebcala.org/unanswered-questions
    Video “Unanswered Questions” On HDNet TV: http://blip.tv/hdnet-world-report/vaccines-and-autism-mixed-signals-5479546.
    Anne Dachel, Media editor: Age of Autism http://www.ageofautism.com/

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    HDNet TV exposed the fact that while health officials continue to tell us studies show no link, the federal government has paid out millions of dollars for compensation for vaccine injuries that included autism.
    http://www.ebcala.org/unanswered-questions
    Video “Unanswered Questions” On HDNet TV: http://blip.tv/hdnet-world-report/vaccines-and-autism-mixed-signals-5479546.
    Anne Dachel, Media editor: Age of Autism http://www.ageofautism.com/

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    Where is even one study on the cumulative effect of the increasing number of vaccines in the childhood schedule? THERE ISN’T ONE.
    http://3.bp.blogspot.com/-arqv6t8VacY/T7QvOcTrpmI/AAAAAAAAD-U/EBqU4n3R0SE/s1600/VaxCDC.png
    Anne Dachel, Media editor: Age of Autism

    • http://www.facebook.com/vitopavlovivit Vito Alexander Pavlovic

      The CDC will be out with a few fake studies, you could count on that.

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    It was the late Dr. Bernadine Healy, former head of the National Institutes of Health, who went on CBS News http://www.cbsnews.com/8301-500803_162-4090144-500803.html in 2008 and said that the vaccine-autism question is still open. She said we need to look at the children who got sick—the ones who were born healthy and were developing normally until they suddenly and dramatically regressed into autism following routine vaccinations. NO ONE IS WILLING TO DO THAT.
    Anne Dachel, Media editor: Age of Autism

  • http://www.facebook.com/people/Anne-Dachel/100000492400392 Anne Dachel

    Our health officials regularly tell us that all their studies show no link between vaccines and autism. Research has shown that every study debunking a link has connections to the vaccine makers.The Centers for Disease Control and Prevention is the place where hundreds of individuals have conflict of interest waivers because they’re also receiving money from the vaccine industry.
    The last head of the CDC, Dr. Julie Gerberding, a long time denier of any link, is now head of the vaccine division at Merck. This is the question CBS News asked in 2008, “How Independent Are Vaccine Defenders?” http://www.cbsnews.com/2100-500690_162-4296175.html
    Anne Dachel, Media editor: Age of Autism

  • Tom

    Multiply the 3.3X increase risk of autism associated with antidepressants by the 6X increase in antidepressant use by women since 1980 in the USA and you get 19X which is disturbingly close to the observed 23X increase in autism over the same period. If some of the autism increase is caused by better reporting, then antidepressants could account for 95% of current autism cases. A depressing ~25% of USA women are now on antidepressants even though there are serious questions whether they even work. It is not completely surprising that something that reportedly affects a stable adult brain might also affect a brain developing and growing in the womb. Is autism the thalidomide disaster of this generation where one of life’s usual miseries, pregnancy nausea, is unknowingly exchanged for a major health disaster?

  • Adam Urato

    TL suggests that it would help to hear from someone from the Massachusetts General Hospital Center for Women’s Mental Health. I welcome other points of view and I have great love and respect for MGH—I trained there as a medical student and resident–but I do not recommend that Center for women seeking advice on this issue. The MGH Center for Women’s Mental Health itself has received significant funding from the antidepressant makers over the years and the researchers in leadership positions at that Center have also received significant funding from the antidepressant makers (see http://www.womensmentalhealth.org/wp-content/uploads/2008/02/Faculty_disclosures_4.11.13_CURRENT2.pdf). Pregnant women and the public deserve untainted advice on this topic—counseling that is free of the bias and/or suggestion of bias that comes with drug industry dollars.

  • T.L.

    It would be great if you could have someone else with a different point of view speak on this issue, such as someone from the Massachusetts General Hospital Center for Women’s Mental Health.