Antidepressants, pregnancy, and autism: the real story / by Methods Man


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If you're a researcher trying to grab some headlines, pick any two of the following concepts and do a study that links them: depression, autism, pregnancy, Mediterranean diet, coffee-drinking, or vaccines.  While I have yet to see a study tying all of the big 6 together, waves were made when a study appearing in JAMA pediatrics linked antidepressant use during pregnancy to autism in children.

To say the study, which trumpets an 87% increased risk of autism associated with antidepressant use, made a splash would be an understatement:

The Huffington post wrote:

The Daily telegraph, rounding up, said:


But if you're like me you want the details. And trust me, those details do not make a compelling case to go flushing all your fluoxetine if you catch my drift.

Researchers used administrative data from Quebec, Canada to identify around 145,000 Singleton births between 1998 and 2009. In around 3% of the births, the moms had been taking anti-depressants during at least a bit of the pregnancy. Of those kids, just over 1000 would be diagnosed with autism spectrum disorder in the first 6 years of life. But if you break it down by whether or not their mothers took antidepressants, you find that the rate of diagnosis was 1% in the antidepressant group compared to 0.7% in the non-antidepressant group. This unadjusted difference was just under the threshold of statistical significance by my calculation, at a p-value of 0.04.

These numbers aren't particularly overwhelming.  How do the researchers get to that 87% increased risk? Well, they focus on those kids who were only exposed in the second and third trimester, where the rate of autism climbs up to 1.2%.  It's not clear to me that this analysis was pre-specified. In fact, a prior study found that the risk of autism increases only when antidepressants are taken in the first trimester:

And I should point out that, again by my math, the 1.2% rate seen in those exposed during the 2nd and 3rd trimesters is not statistically different from the 1% rate seen in kids exposed in the first trimester. So focusing on the 2nd and 3rd trimester feels a bit like cherry picking.

And, as others have pointed out, that 87% is a relative increase in risk. The absolute change in risk remains quite small. If we believe the relationship as advertised, you'd need to treat about 200 women with antidepressants before you saw one extra case of autism.

But I'm not sure we should believe the relationship as advertised. Multiple factors may lead to antidepressant use and an increased risk of autism. Genetic factors, for example, were not controlled for, and some studies suggest that genes involved in depression may also be associated with autism. Other factors that weren't controlled for: smoking, BMI, paternal age, access to doctors. That last one is a biggie, in fact. Women who are taking any chronic medication likely have more interaction with the health care system. It seems fairly clear that your chances of getting an autism diagnosis increase with the more doctors you see. In fact, in a subanalysis which only looked at autism diagnoses that were confirmed by a neuropsychologist, the association with antidepressant use was no longer significant.

But there's a bigger issue, folks – when you take care of a pregnant woman, you have two patients. Trumpeting an 87% increased risk of autism based on un-compelling data will lead women to stop taking their antidepressants during pregnancy. And that may mean these women don't take as good care of themselves or their baby. In other words, more harm than good.

Could antidepressants increase the risk of autism? It's not impossible. But this study doesn't show us that. And because of the highly charged subject matter, responsible scientists, journalists, and physicians should be very clear. Women taking anti-depressants during pregnancy, do not stop until, at the very least, you have had a long discussion about the risks with your doctor.