Antidepressants, Pregnancy, and Autism: Really Time to Worry

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.