Pregnant women who have depression face a difficult decision when it comes to using antidepressants to treat their symptoms. On one hand, treating depression is critical for the mother’s wellbeing, and that translates to the baby’s health, as well. But some studies have shown that being exposed to antidepressants in utero can contribute to an increase in developmental conditions, including attention deficit hyperactivity disorder and autism. To make matters more confusing, other research has shown that the drugs are safe for the developing fetus.
Now, a series of new reports suggests that antidepressants may not pose as high a risk for autism as previously thought. In two papers published in JAMA, researchers found that other factors, including genes linked to mental illness, may be more strongly associated with autism than exposure to antidepressants. Another new paper in JAMA Pediatrics similarly found that studies on the subject aren’t consistent in how they account for such possible alternative contributors to autism.
Brian D’Onofrio, director of clinical training in the department of psychological and brain sciences at Indiana University and a co-author of one of the JAMA papers, says that studies on antidepressants and autism haven’t been able to distinguish the effects of the drugs from the effects of depression. Several large studies have found that women who took antidepressants during pregnancy were more likely to have children with autism, yet the question of whether that link was due to the medication—or the other factors that contribute to depression—remained, D'Onofrio says. "Women who use antidepressants, for example, are much more likely to have severe depression and even poorer prenatal care."
So D’Onofrio analyzed data from more than 1.5 million children whose mothers reported on whether they used antidepressants during pregnancy. He and his colleagues parsed the data in different ways to tease out the effects of the drug from the effects of other autism contributors. In one analysis, he compared siblings who were born after their mothers had used antidepressants while pregnant to those born when their mothers hadn’t used the drugs. It turned out that rates of autism weren’t that much different among these brothers and sisters. This suggests that the antidepressants weren’t the major contributor to the autism, and that something else in the children’s experience—like their genetics or the environment in which they were raised, which could include the effect of their mother’s depression on their development—played a greater role than the drugs.
He and his team also compared children born to mothers who used antidepressants before pregnancy, but not during pregnancy, to those whose mothers began using the medications during pregnancy. They even looked at fathers’ use of antidepressants to determine if genetic factors were more likely to contribute to autism risk.
“If you just look at the population as a whole, children born to women who take antidepressants are more likely to be diagnosed with autism than children born to mothers who don’t take them,” says D’Onofrio. “But when you try to account for all the other factors that could help explain that association, like comparing siblings and looking at the timing of the exposure, the association went away. That suggests that the link is not due to the actual exposure from the drugs during pregnancy, but due to other factors.”
In another study in the same issue of JAMA, Dr. Simone Vigod from the Women’s College Research Institute and her team came to a similar conclusion after carefully looking for other possible connections between antidepressants and autism. She studied more than 35,000 births and also compared rates of autism among brothers and sisters whose mothers used antidepressants during some pregnancies but not others. Like D’Onofrio, she also found that women who used antidepressants did have an increased risk of having children with autism, but that the connection disappeared when she accounted for things such as the severity of the mom’s depression and other medications that the mom may have been taking. “Previous studies accounted for four, five or six possible factors, usually environmental factors like maternal age and socioeconomic status,” she says. “Very few accounted for the severity of maternal depression, and very few accounted for other medication exposures.”
Both studies highlight the fact that autism is a complex condition that is likely caused by a number of different converging factors: genetics, in the form of genes from both mother and father for conditions like depression or other mental illnesses, as well as environmental influences associated with life stresses that can be both psychological as well as physical, such as poverty. A better understanding of these other factors could help clarify what role, if any, antidepressants during pregnancy actually play in autism.
In the final study, published in JAMA Pediatrics, Dr. Florence Gressier from University of Paris-Sud, in France, agrees that better studies are needed on the topic. Her analysis found that studies are inconsistent in how they account for things like a mother's depression and environmental factors that could link antidepressants and autism. That means their results are hard to interpret.
For now, the experts say that the latest data should give parents reassurance that antidepressants don’t necessarily raise autism risk. “When taking everything together, it’s quite reasonable to say that these are low-risk medications, especially when you consider the potential risk of not taking them for some women,” says Vigod. “Women with children with autism worry that they did something wrong. These data should be reassuring that the likelihood autism is related to taking antidepressants is pretty low.”