Children whose mothers use antidepressants during pregnancy may be more likely to develop autism than kids whose mothers do not, say researchers in California.
In a study involving data on more than 1,800 children — fewer than 300 of whom had an autism spectrum disorder (ASD) — and their mothers, the scientists found that women who were prescribed drugs to treat depression in the year before giving birth were twice as likely to have children with an ASD, compared with women who did not take antidepressants. The risk was even greater for women who were prescribed the drugs in the first trimester: their children were nearly four times more likely to develop autism or a related disorder.
The study focused on one type of antidepressant, selective serotonin reuptake inhibitors (SSRIs), a class of drug that includes fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft). These antidepressants work by increasing available levels of the neurotransmitter serotonin surrounding nerve cells in the brain, which helps boost mood.
The authors of the study were interested in investigating SSRIs in particular because there is growing evidence that serotonin may play a role in the development of autism. Some studies have found that children diagnosed with the disease tend to have higher levels of serotonin in their blood, and family members of children with autism also show slightly higher levels of the neurotransmitter than those in families without autistic members.
Confusing the issue is the question of whether it is the SSRI or the underlying depression that the drug is prescribed to treat that really affects autism risk. After all, a family history of mental health problems is common among people with autism; studies show that mothers of autistic children tend to have higher than expected rates of depression, anxiety and other mood-related disorders.
So Lisa Croen, director of the Autism Research Program at Kaiser Permanente, and her colleagues designed a study to tease apart these two contributing factors. From Kaiser Permanente’s database of more than 3.2 million people, the researchers identified 298 children with autism who were born between 1995 and 1999. They matched these kids with 1,507 children without autism who were born at roughly the same time and in the same hospitals.
The researchers then checked to see which women had filled prescriptions for SSRIs in the year before delivery: the mothers of 20 children with an autism spectrum disorder had taken antidepressants, compared with mothers of 50 children without an ASD.
The authors also looked at which mothers had a history of depression or another mental-health problem: that included about 12% of mothers whose children had an autism spectrum disorder, and 9% of mothers whose children did not. But when researchers adjusted for mental-health history, the association between SSRI use and autism persisted.
“Almost everybody getting an antidepressant has some mental health disorder, and our study adds to the body of knowledge that shows that a family history of mental health problems may be associated with autism,” says Croen. “But our study indicates that it isn’t necessarily the mental health disorder, it was the treatment. When we controlled for the treatment, we didn’t see any association or any increased risk of autism associated with maternal depression or anxiety.”
That raises a tricky question for moms-to-be and their doctors. Anywhere from 7% to 13% of women are treated for depression during their pregnancy; leaving depression untreated could interfere with a healthy pregnancy and birth, not to mention the forging of a strong bond between mother and baby after birth. Treating maternal depression may also help prevent the devastating effects of postpartum depression. But how should moms and doctors weigh this potential added risk of autism associated with SSRIs?
“We definitely don’t want women to stop taking their medications based on the findings of this study,” says Croen. The Food and Drug Administration classifies most antidepressants in Category C, which means that they have been proven neither safe nor unsafe for use in pregnancy (Category A and B drugs are safer, while Category D and X include drugs whose risks outweigh the benefits for fetuses or should be avoided altogether).
Dr. Mason Turner, assistant director of regional mental health in northern California for Kaiser, agrees. “Even before the study, women have had concerns about taking medication during pregnancy,” he says. “I expect that the results will mean that we will see a lot more discussion and that more women may say, let’s talk about some alternatives [for treating depression]. That discussion should include ways to treat depression that are not medication oriented, such as stress reduction, psychotherapy and support groups; what support the woman can expect from her partner and family; and how reducing her work hours may help address the depression. We may try a combination of these things first, and if they are not working, then talk about the need for medication.”
Croen points out that since autism is a complex disorder with genetic and environmental contributors, there may still be some underlying factor related to depression or other anxiety disorders that also influences autism risk. “There may be some kind of genetic susceptibility in mom that is associated with a tendency for depression and may also be associated with an increased risk of developing autism in her child,” she says. “That may be bringing these pieces — autism, depression and SSRIs — together but it’s not the depression per se or the treatment for depression; they may simply be markers for this other susceptibility.”
Finding that factor — or factors — will certainly be the subject of future research. In the meantime, mental health experts are hoping that the findings generate some important discussions between expectant moms and their doctors about depression. “Nothing in the study suggests that we should stop prescribing SSRIs during pregnancy,” says Turner. “It’s more about increasing the conversation, discussing options that are available and understanding the risks, both of depression and of the treatment.” It’s all about balance, he says, which will be different for each woman.
The study was published online by the Archives of General Psychiatry.