April 22, 2013, 11:57 am
Study Links Autism With Antidepressant Use During Pregnancy
By KJ DELL'ANTONIA
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
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
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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