April 22, 2013, 11:57 am 
Study Links Autism With Antidepressant Use During Pregnancy
A cautiously worded study based on data collected in Sweden has found that “in 
utero exposure to both selective serotonin reuptake inhibitors (S.S.R.I.’s) and 
nonselective monoamine reuptake inhibitors (tricyclic antidepressants) was 
associated with an increased risk of autism spectrum disorders, particularly 
without intellectual disability.”
The Swedish medical birth register (which contains data on current drug use 
reported by mothers early in their pregnancies), along with a system of 
publicly funded screenings for autism spectrum disorders and extensive national 
and regional registers of various health issues, make a detailed, 
population-based case-control study possible — one that controls for other 
variables like family income, parent educational level, maternal and paternal 
age and even maternal region of birth (all factors the authors note have been 
previously associated with autism). 
This is the second study in two years to associate antidepressant use during 
pregnancy with an increased incidence of autism in exposed children. An 
earlier, smaller study in California also found a modest increase in risk. The 
Sweden-based study could not (and did not) exclude the possibility that it was 
the severe depression, rather than the use of antidepressants, that created the 
association, but the smaller California study (which considered only 
S.S.R.I.’s) found “no increase in risk” for mothers with a history of mental 
health treatment in the absence of prenatal exposure to S.S.R.I.’s.
The authors of the current study took a very cautious approach to their 

The results of the present study as well as the U.S. study present a major 
dilemma in relation to clinical advice to pregnant women with depression. If 
antidepressants increase the risk of autism spectrum disorder, it would be 
reasonable to warn women about this possibility. However, if the association 
actually reflects the risk of autism spectrum disorder related to the 
nongenetic effects of severe depression during pregnancy, treatment may reduce 
the risk. Informed decisions would also need to consider weighing the wider 
risks of untreated depression with the other adverse outcomes related to 
antidepressant use. With the current evidence, if the potential risk of autism 
were a consideration in the decision-making process, it may be reasonable to 
think about, wherever appropriate, nondrug approaches such as psychological 
treatments. However, their timely availability to pregnant women will need to 
be enhanced.
Others working in the field are more inclined to draw a line between the 
prenatal drug exposure and the increased risk of autism. “It really shouldn’t 
come as that much of a surprise given that numerous animal studies have shown 
that exposure during development leads to changes in the brain and changes in 
behavior — often that mimic autism,” said Dr. Adam C. Urato, assistant 
professor of obstetrics and gynecology at the Tufts University School of 
Medicine and chairman of the department of obstetrics and gynecology at 
MetroWest Medical Center in Framingham, Mass. (Dr. Urato obviously didn’t speak 
in links, but you can find the animal studies he refers to here and here.) 
“And why should it surprise us that medications that can change brain chemistry 
and function might alter the development of the brain and behavior?” Dr. Urato 
argues that the risks of antidepressant use during pregnancy outweigh what he 
sees as the limited benefits. 
One conclusion that is simple to draw is that it’s extraordinarily difficult 
for a pregnant woman with clinical depression to find some definitive answer 
about what’s best for her in her situation. I’ve spoken to other researchers in 
the past who have described for me how difficult it is to put together a study 
that separates the risks of depression itself in pregnancy from the risks, if 
any, of the drugs used to treat it. As the researchers in Sweden note, it’s 
unlikely that conclusive evidence on this issue will ever be available. 
If you’ve been pregnant with clinical depression, where did you go to find the 
information and advice you needed?
Updated | May 29, 2013: An earlier version of this update quantified the 
“modest” increase in attributable risk as 0.6 percent in the studied 
population. While Dr. Dheeraj Rai, one of the authors of the study, confirmed 
this figure, a number of readers and medical professionals raised questions. So 
we went back to Dr. Rai for further explanation. Here is what he wrote:
“The subject of antidepressant use during pregnancy, and any possible 
association with autism, is one that understandably evokes great emotion — even 
more so because at the current stage we don’t have a definitive answer. Readers 
of our paper may be confused about the two different statistics presented in 
our paper, I will try and explain what each of them means. 
The first statistic (odds ratio) conveys whether mothers of individuals with 
autism were more likely to report antidepressant use during pregnancy. In our 
study, we found that mothers of children with autism were over 3-fold more 
likely to have reported using antidepressants during their first antenatal 
interview than mothers of children without autism. Unfortunately, we were 
unable to clearly say whether this increase in risk of autism was directly 
related to the antidepressant, or whether it was due to the underlying 
depression for which the drug was prescribed. We therefore suggest caution in 
interpreting this finding.
The second statistic we reported in our paper was called ‘population 
attributable risk’. This was an estimate of the percentage of autism cases that 
could be prevented in the population, assuming antidepressants caused autism 
and we prevented every single woman in the study population from taking these 
medications during pregnancy. This population attributable risk for our Swedish 
study population was under 1%. This statistic may differ from population to 
population, depending upon how common antidepressant use during pregnancy is. 
For instance, in the other recent study on this topic, Dr Lisa Croen and 
colleagues found this attributable risk to be less than 2.5% in their Northern 
California population. This rules out antidepressant use, if causal, as a 
factor explaining the rising prevalence of autism since it explained very few 
autism cases.”

Follow KJ Dell’Antonia on Twitter at @KJDellAntonia or find her on Facebook and 

Dr. Roger B Clough NIST (ret.) [1/1/2000]
See my Leibniz site at

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