By RACHEL RABKIN PEACHMAN
Credit Illustration by Allison Steen
The pros and cons of taking antidepressants while pregnant have been hotly debated despite increasing research in the field. Each time one study highlights negative outcomes associated with antidepressant use during pregnancy, another study is published pointing toward the benefits for mother and baby. For any woman considering pregnancy and in need of antidepressants, deciding on a course of action can be agonizing. Today, research published in JAMA Pediatrics is likely to make matters even more troubling for these women.
The large observational study, led by Anick Bérard, Ph.D., professor of perinatal epidemiology at the University of Montreal, found that taking antidepressants — particularly selective serotonin reuptake inhibitors, commonly called SSRIs — during the second or third trimester of pregnancy is associated with an 87 percent increased risk of autism spectrum disorder in children. That headline-provoking number represents a relatively large associated increase in what begins as a small number: Among the pregnancies studied, the rate of diagnosis of autism rose from less than 1 percent to less than 2 percent of children when the mothers were taking antidepressants. The findings were based on all pregnancies in Quebec between January 1998 and December 2009, and included 145,456 pregnancies that resulted in full-term, singleton babies.
“We’re not the first paper on this topic, but we’re the first one with such a large sample size,” said Dr. Bérard, who also, as is disclosed in the paper, was a consultant for plaintiffs in the litigation involving antidepressants and birth defects. “So of course it sounds alarming; it’s almost two times the risk of autism.”
It certainly does sound alarming and no doubt may frighten many would-be mothers, especially considering that from 14 percent to 23 percent of women experience depressive symptoms while pregnant. But it’s important to put the numbers in perspective and remember that we’re still talking about less than 2 percent of children. “The absolute risk in this study is very small,” said Kimberly A. Yonkers, M.D., professor of psychiatry, epidemiology and obstetrics and gynecology at the Yale School of Public Health.
I called Dr. Yonkers because the last time I spoke with her (for New Research on Antidepressants and Pregnancy Finds No Link to Athsma) about this topic, her take was that the jury was still out on whether antidepressants are harmful to fetuses. So I wondered, would this new study change her thinking?
“I don’t want to be an apologist for antidepressants during pregnancy, but I always have to look with a certain degree of skepticism at cohort studies — which I think are invaluable and I have published them myself — but they also have issues,” said Dr. Yonkers, who is also the director of the Center for Wellbeing of Women and Mothers at Yale. One of the primary limitations of observational studies like these, she explained, is that no matter how carefully researchers aim to evaluate each risk factor, it’s often extremely difficult to tease them apart — particularly in this case in which autism spectrum disorder and depression share some of the same environmental and genetic risk factors.
And at this point, it remains unclear how depression, antidepressants, genetics or other environmental factors may interact to result potentially in a diagnosis of autism. Dr. Bérard, the study author, was quick to point this out as well: “The causes of autism are still unknown,” she said. “We’re starting to understand it but we’re far from really understanding the whole mechanism. “We studied one of multiple environmental causes and measured an association. It’s not a cause.”
Still, she added that this association is consistent with some other observational research that has been published. And when it comes to studying pregnancy and antidepressants, observational research is the best we’ve got. Though randomized controlled trials are considered the gold standard in determining cause and effect, they are not an option in this field. It would be unethical for researchers to assign pregnant women randomly to one group or another that could potentially harm a baby. When controlled trials are unavailable (as they often are in issues of health) experts in this arena must rely on observational studies and hope that once enough of them show similar associations time after time, causal effects will start to emerge.
Take the example of smoking and lung cancer. “There’s no doubt in anybody’s mind that smoking causes lung cancer,” said Dr. Bérard. But that was not the case when researchers first began studying the association between cigarettes and cancer. It took years of observational research “with multiple studies of different populations with different observational designs and with different limitations always showing the same thing. And now there is no doubt that there is a causal association.” This kind of research into pregnancy, she said, should be viewed as part of a growing picture that is still far from complete.
It’s also far easier to reach a definitive conclusion with respect to smoking — a recreational activity that doesn’t in itself offer medical benefits. Suggesting that people may be better off quitting is not likely to harm them, and may in fact help them. Taking antidepressants, on the other hand, is an established treatment for very real psychiatric conditions, and suggesting that the medications are dangerous to fetuses — before all the observational evidence is in — could have disastrous results.
“I have seen people terminate pregnancies because they’re so psychiatrically ill and they’re afraid to be treated because they’re afraid that their baby is going to be exposed to a psychotropic agent,” Dr. Yonkers said.
What is more, “untreated maternal depression is associated with a host of other complications,” wrote Bryan H. King, M.D., professor of psychiatry and behavioral sciences at the University of Washington and the director of the Seattle Children’s Autism Center, in an editorial that accompanies this new study. Research has found these complications to include preterm birth, an increased risk of asthma in children and elevated cortisol levels in babies, which may have lifelong effects on those children’s brains.
So then what are we to make of this new study? Should it influence how pregnant women and their doctors approach antidepressants? Perhaps, Dr. Bérard suggested, after noting that women should talk with their doctors about their medications and options first. “We’re not saying, ‘do not treat depression.’ We will never say that. It’s a very severe and debilitating condition and is associated with a lot of co-morbidities,” she said. “Of course treat depression, but maybe treat it differently, at least during pregnancy.” She added that exercise and psychotherapy have each been shown to help alleviate mild to moderate depression.
And what if exercise and talk therapy are not enough? “What this says to me — and this hasn’t changed — is that people should take a medication during pregnancy if they absolutely need it,” Dr. Yonkers said. “If they don’t need it, they should not take it.”
It sounds simple enough. But it’s not always simple to figure out if you need antidepressants. I speak from experience. I took antidepressants during pregnancy after trying many other treatment approaches. And even though I was armed with information and the benefit of thoughtful health care providers, it was one of the hardest decisions I’ve had to make in my life.
So, while I know that this study may make that same decision harder for other pregnant women, my hope is that it does not scare women from seeking treatment. Instead, I hope women and their clinicians consider the entire body of research on depression and antidepressant use during pregnancy to help guide women as they navigate their way into motherhood.