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 findings:



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.”