Autism, Antidepressants, and Pregnancy: The Basics

Adam Urato, MD
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This month, the seventh study and eighth study came out on the topic of antidepressant exposure during pregnancy and autism.  And these studies showed, as essentially all of the others have, that antidepressant use during pregnancy (principally with selective serotonin reuptake inhibitors or SSRIs) is associated with autism in the exposed children.

With so many children being diagnosed with autism and so many women taking antidepressants during pregnancy, everyone wants to know: are these things (the antidepressants) associated with autism or not?  Quite frankly no one has the time to read through all eight scientific papers (and dozens more animal and basic science studies) to understand this important area, so I will do my best to briefly summarize it here.

Basic Science Evidence

It is a scientific fact that serotonin plays a crucial role in the development of the embryonic (up to 10 weeks gestation) and fetal (from 10 weeks gestation until delivery) brain.  No one can question that.  Serotonin is a crucial neurotransmitter and cell signaling molecule that is vital for the formation of the fetal brain (and in many other body systems).  The SSRI antidepressants alter the serotonin system—this is indisputable as well.  SSRIs are not naturally occurring substances that depressed patients are deficient in.  The SSRIs aren’t like insulin for diabetics.  These SSRIs are synthetic chemical compounds that alter the serotonin system.  So with the use of SSRIs during pregnancy, what we have is exposure of the developing brain and its crucial serotonin system to synthetic chemical compounds that alter that very system.

Animal Evidence

I could list the dozens of studies in animals that show that animals that are exposed to SSRI antidepressants during development go on to develop changes in their brains and behaviors—with findings that often mimic autism.  Fortunately, these studies have been nicely summarized in the following scientific papers (Olivier, 2013 and Borue, 2007).  One statement really stands out to me from the Olivier paper:  “Overall, early exposure to SSRIs has an effect on brain development and neuroplasticity which can markedly alter the behavior of the offspring.”  And the following statement can be found in the Borue abstract:  “Experimental studies in rodents show that administration of SSRIs during a key developmental window creates changes in brain circuitry and maladaptive behaviors that persist into adulthood.”  For animal researchers, it is clear what happens when we expose developing animals to SSRIs.  The simple bottom line is that these drugs appear to “mess up” these animals’ brains.  And what we see are animals with altered brain structure and maladaptive behaviors.

Human Evidence on Antidepressants, Pregnancy, and Autism

The eight human studies that have looked at this area are as follows:

  1. Croen, 2011
  2. Rai, 2013
  3. Sorensen, 2013
  4. Hviid, 2013
  5. Harrington, 2014
  6. Gidaya, 2014
  7. El Marroun, 2014
  8. Clements, 2014

As you can see, there has been a lot of interest in this area lately.  Seven of the eight papers are in the last 2 years.  And what do these studies show us?  Understood together, they are clearly pointing in the same direction as the basic science data and the animal studies—that exposure to the SSRI antidepressants during development leads to brain changes—in this case autism.  In the interest of time I won’t go into each study in detail, but a few key points must be noted.  First, a statistically significant result was not attained in the eighth study after multiple statistical corrections were performed, so we cannot be 95% certain of the association. But I don’t think we need 95% certainty on this association before warning the public.  The public wants us to be 95% sure that drugs are safe—not the reverse.  The public doesn’t want us to withhold warnings unless we are 95% sure that drugs are causing harm.

Second, the Hviid study got a lot of press because it was published in the New England Journal of Medicine and many news outlets covered this research with headlines reassuring the readers that antidepressants are not associated with autism.  But look at the Gidaya, 2014 “critique” of that study.  It’s clear to me that the data set from Denmark (which has now been studied by Sorensen, Hviid, and Gidaya) shows these medications to be associated with autism.  The Harrington study is particularly crucial because these researchers focused on what happens to boys who are exposed.  Boys with first-trimester exposure were more than three times as likely to develop autism (OR: 3.22; 95% CI: 1.17-8.84) and boys with third-trimester exposure were almost five times as likely to have developmental delay (OR: 4.98; 95% CI: 1.20-20.62).  As more scientific evidence accumulates, it is becoming clearer that antidepressant exposure during pregnancy has different effects on boys compared with girls.  Harrington found dramatic increases in problems in exposed boys.

Advice Tainted by Drug Company Dollars

In the latest study (Clements, 2014), the authors showed that antidepressant use during pregnancy is associated with ADHD in children.  (They also showed an association with autism that was not statistically significant.)  However, in the paper itself and in the press release that accompanied the study, these authors downplayed the risks of using these drugs in pregnancy.  The overall “spin” from the paper and press release could be interpreted as being quite favorable to the continued use of these drugs in pregnancy.  And were some of these researchers being paid by the antidepressant makers?  I have included below the conflict of interest statement from the paper:

CONFLICT OF INTEREST

Dr Perlis has received consulting fees or served on scientific advisory boards for Genomind, Healthrageous, Pamlab, Perfect Health, Pfizer, Proteus Biomedical, Psybrain and RIDventures, and received patent fees/royalties from Concordant Rater Systems (now UBC/Medco). Dr Smoller is a member of the Scientific Advisory Board of Psybrain, Inc. Dr Fava reports the following: Research Support: Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., Wyeth-Ayerst Laboratories. Advisory/Consulting: Aspect Medical Systems, Astra-Zeneca, Bayer AG, Biovail Pharmaceuticals, Inc., BrainCells, Inc. Bristol-Myers Squibb Company, Cephalon, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithkline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lundbeck, MedAvante, Inc., Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Wyeth-Ayerst Laboratories. Speaking: Astra-Zeneca, Boehringer- Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Novartis, Organon Inc., Pfizer Inc, PharmaStar, Wyeth-Ayerst Laboratories. Equity Holdings: Compellis, MedAvante. Royalty/patent, other income: none. The remaining authors declare no conflict of interests.

By my count that is 52 pharmaceutical companies!  This situation is not unique to this scientific paper or this research group.  If you look at the experts who have been advising the public on the use of antidepressants in pregnancy over the past decades you will see again and again and again that they are being paid by the very drug companies that make the antidepressants.  Again and again they reassure us about the use of these drugs in pregnancy, while receiving pharmaceutical company dollars.  The public has every right to view this advice as tainted and to assume that all of this money flowing to these experts and their institutions is having a corrupting influence.

This is Not Fearmongering

I’m concerned that the public may lump antidepressant use during pregnancy in the same category as so many of the other things that someone somewhere has associated with autism.  A simple internet search on the topic brings up cell phones, microwave ovens, and many other possible causes.  And it’s easy to dismiss the whole area as fearmongering.  But the evidence supporting the link between antidepressant use during pregnancy and autism is solid and not simply a sensationalistic effort to grab headlines.  As I have documented here, there are dozens of studies ranging from basic science to animal studies to human data that support this link.

Is it Dangerous to Publicize This Link Between Antidepressants During Pregnancy and Autism?

I think that there is a fear amongst some in medicine and the press that publicity regarding this link may lead some women to stop taking these drugs—and with bad consequences (eg worsening depression, suicide, etc.)  I can certainly understand this concern, but the bottom line is that we need to accurately inform pregnant women and the public about what the scientific studies are showing.  Also, it must be kept in mind that the SSRI antidepressants have an FDA black box warning on them because of their link to increased suicidal thinking and behaviors.  The best available evidence shows increased rates of suicide with the use of antidepressants by young women and not a protective effect.

Furthermore, there is now very good evidence that for many patients, nondrug approaches to depression (eg exercise and psychotherapy) are as good as—if not better than—use of drugs.  Depressed pregnant women should not be ignored–they need good treatment and care.  And efforts to inform the public of the dangers of use of antidepressants in pregnancy should NOT be seen as an attempt to dismiss the importance of depression.  The key issue is how best to treat depressed pregnant women.  It’s becoming clear that our current approach—which often involves the use of synthetic chemical compound antidepressants—is altering fetal development and having disastrous consequences in many cases.

Beyond Autism

The track record for what happens when you expose developing babies to synthetic chemical compounds is not a good one.  Time and again we have seen that pregnancy exposures can have tragic consequences (eg DES and Thalidomide).  And that is just simple common sense.  This really isn’t rocket science.  The SSRI antidepressants are synthetic chemical compounds that alter the serotonin system (and other brain and body systems as well.)  These drugs are clearly associated with pregnancy complications (like miscarriage, birth defects, preterm birth, low birth weightpreeclampsia, newborn behavioral syndrome, persistent pulmonary hypertension of the newborn, neonatal heart conduction (EKG) changes, and newborn seizures) and there is no scientific evidence that they are improving outcomes for moms and babies.  It’s time to get this information out to pregnant women and the public and to prioritize non-drug approaches to mental health.

9 COMMENTS

  1. Giving these chemicals to expecting mothers, that’s just way way beyond stupid.

    The thalidomide disaster is one of the darkest episodes in pharmaceutical research history. The drug was marketed as a mild sleeping pill safe even for pregnant women. http://www.google.com/search?q=thalidomide

    I mean what the hell , adults take these SSRI drugs and then get all kinds of sick from withdrawals the marketing “pharma fraud” dept claimed did not exist till people started getting sick and speaking out. SSRI withdrawal and brain zaps , great idea subjecting newborns to that too.

    Who are these people who do pharma’s dirty work ? When I first started reading MIA I used to ask myself how can these pharma people lie and commit all the crimes I read about on these pages that harm so many people with zero remorse ? I found my answer.

    Snakes in Suits: When Psychopaths Go to Work is a book by industrial psychologist Paul Babiak and psychopathy expert Robert D. Hare. A compelling, frightening, and scientifically sound look at exactly how psychopaths work in the corporate environment http://www.mtpinnacle.com/pdfs/psycophaths-at-work.pdf

    The snake in the suit say’s lets target children and expecting mothers, profits people profits !

    • In case of pregnant women the precautionary principle should be used every time unless there is immediate threat of death or serious disability. Pregnant women should not even take aspirin and other commonly used meds which are otherwise relatively safe – giving them heavy duty psych drugs is criminal. Every moderately intelligent physician should know better than prescribing antidepressants to an expecting mother.

  2. You say:

    boys with third-trimester exposure were almost five times as likely to have developmental delay (OR: 4.98; 95% CI: 1.20-20.62)

    But an odds ratio (OR) of 5 between A and B does not mean that A is 5 times more likely than B.

    Example: The odds of flipping heads on a coin are 1:1 (probability 50%). The odds of rolling a 6 on a die are 1:6 (probability 17%).

    The odds ratio between the two is (1:1) / (1:6) which equals 6. However you are not six times more likely to flip heads than to roll a 6. You are only three times more likely (50 / 17 = 2.9).

    http://en.wikipedia.org/wiki/Odds_ratio#Example

    IMO this is a pretty bad error to commit on a post of this nature.

  3. Excellent article. I searched this up because I’ve noticed in my friend group (I live in Utah) a high percentage of children with autism. In each family (I know several) the mother (and sometimes the father as well) is taking an antidepressant drug. I don’t know much about these drugs but in my mind I put the two together and searched up state by state antidepressant use rates and autism rates. Utah is #1 in antidepressant use. Utah was #1 on the autism rate as well – apparently it is now #2 as New Jersey has taken the lead. #1 or #2 in autism rates and #1 in antidepressant use rates… honestly, I don’t need 8 (or even 2) studies paid for by pharma groups – I can put 1 and 2 together on my own… Thank you for putting this well through out piece together.