We’re beginning to learn how moms’ antidepressants can affect fetuses

Antidepressants are now among the drugs most commonly used by Americans — but the decision to take them or stay on them can be especially fraught for women considering motherhood.

On the one hand, we now know that women with depression and their babies are at a higher risk of all kinds of health problems — like preterm birth, a lower birth weight, and postpartum depression. And we have drugs that can potentially alleviate moms’ symptoms, including antidepressants.

These days, about 5 percent of expectant mothers use antidepressants, most commonly, serotonin reuptake inhibitors, or SSRIs, such as citalopram (brand name Celexa), paroxetine (Paxil), or sertraline (Zoloft).

Now here’s the dilemma: While the risks of depression in pregnancy are well-documented, there’s a lot we don’t know about the risks of moms taking antidepressants — in particular, how the medicines affect their babies.

There’s no easy answer to what women on antidepressants should do during pregnancy. And a new study out today in the journal JAMA Pediatrics may complicate matters. It suggests SSRI use among mothers may interfere with fetal brain development, especially in the regions of the brain associated with emotions.

But don’t go running to tell your pregnant friends to chuck their SSRIs just yet. Jiook Cha, an assistant professor of neurobiology at Columbia University Irving Medical Center, tells me researchers still have a lot of unanswered questions. The new paper, while intriguing, is preliminary. Still, it’s a good excuse to walk through what we know and don’t know about this common question.

Depression is twice as common in women as it is in men. Pregnancy can make it worse.

Depression affects 16 million Americans every year — but being a woman is a risk factor for the condition. Depression is twice as common in women as it is in men. In one study, for example, the 12-month prevalence of depression in females was 8 percent, while it was only 4 percent in men.

Pregnancy, and the severe hormone changes it brings, can put women at an even greater risk. Between 14 and 23 percent of pregnant women experience depression while they’re expecting, according to the Mayo Clinic. That means many women end up grappling with the question of what to do with their depression, and medications for it, during pregnancy.

At a time when women are expected to be joyful, these lows can be especially alienating and stigmatizing. Women who are prone to depression are especially vulnerable while expecting — though other risk factors include maternal anxiety, life stress, lack of social support, and domestic abuse.

The standard US guidelines now recommend screening for depression throughout pregnancy and suggest women with mild to moderate symptoms opt for psychotherapy first, while those with more severe depression consult their doctors about trying (or continuing to take) antidepressants. But many women face hard and confusing choices here, and there are many questions that still need to be resolved by science.

The shoddy evidence on antidepressants in pregnancy

Before we dive into the research on pregnancy and antidepressants, know this: Most studies in this area aren’t very high quality, and there are no randomized trials because researchers aren’t allowed to do them. Instead, there’s lots of observational research — which look at associations between women on antidepressants and certain health outcomes in their babies — and they’re often biased by design.

According to Lauren Osborne, the assistant director of Johns Hopkins Women’s Mood Disorders Center, who has analyzed the research, most studies compare depressed pregnant women who were taking antidepressants to healthy pregnant women — so there may be more that differs between the two groups than just the use of antidepressants.

Women on antidepressants may have other medical and psychiatric problems and use other medications to control them, which may also confound the results too. “Therefore if you find a risk associated with SSRI use, it might just be that SSRI use is a marker for a group of women who is very different,” she added.

Still, in the studies we do have, some risks and questions have emerged. Among the most important, according to UpToDate’s summary of the evidence: SSRIs have been associated with preterm birth (before 37 weeks as opposed to the full 40), though it’s not clear how much of an impact that has on clinical outcomes.

Importantly, SSRIs don’t appear to increase the risk of birth defects — with the possible exception of the drug paroxetine, which has been linked to an increased risk of congenital heart defects in some studies.

Overall, though, there are no major suggestions of harm. And doctors have been operating under the assumption that the risks of leaving moderate or severe depression untreated — for both mom and baby — typically outweigh the known risks associated with antidepressants.

The effects of antidepressants on neurodevelopment are less well known

Enter the new study. Researchers used magnetic resonance imaging (or MRI scans) to examine associations between SSRI use and brain development in 98 newborns of women, including 16 moms taking SSRIs, 21 untreated women with depression, and 61 in a healthy control group.

In line with research from previous animal studies, the researchers found an association between prenatal exposure to SSRIs and increases in the volume of several areas of the brain, including the amygdala and the insular cortex.

Cha, the study author, emphasized that while he was surprised to have found this link, the study was preliminary and “our data need to be replicated and rigorously tested against confounders in order to make a firm conclusion.” So the study suggests a “potential” association and more research is needed.

Indeed, there were a number of important limitations to the research that should make any reader pause. Osborne pointed out that researchers have previously shown that amygdala volumes are different in babies of moms with depression, irrespective of antidepressant use, and that moms who have inflammation in pregnancy also have different amygdala volumes. “So is this a finding unique to SRRIs?” she asked. We don’t yet know.

“We don’t know how well the drugs work in pregnant women”

We also don’t know the long-term significance of the finding for infants’ cognitive and emotional development. Nor we know what role, if any, anxiety play here.

“There are other reasons for using SSRIs than depression. They are gold-standard treatment for anxiety,” Osborne added. Researchers have found that anxiety is more common than depression in pregnancy and that an overactive amygdala is linked with increased anxiety. “We don’t have any measure of anxiety for women in this study.” So it may be the anxiety, not the antidepressants, that’s causing the brain restructuring.

While the researchers tried to overcome the problem in other studies, which have often compared only healthy women and their babies to depressed women, there were some problems with their groupings. The women on SSRIs were overwhelmingly white and high-income compared to the women with untreated depression and the healthy women. So there may be differences between them and the other groups beyond what medications they were on.

That means the study shows differences in brain development of unknown clinical significance in groups of women who may not have been comparable. “It’s great that researchers have started to look at the effects of drugs on human brain development,” Osborne said, “but we now [need to] take it to the next step and look at it in a way that compares groups that are actually comparable.”

There’s another even bigger question at issue here. “We don’t know how well the drugs work in pregnant women because nobody studies this specific question,” Osborne added. Many women who take antidepressants during pregnancy become ill, for example, but under-dosing is a rampant problem during pregnancy, so it might be that, and not the medications, causing the problems. Plus, antidepressants even at the best of times are an imperfect fix for depression.

For now, Cha suggested women work with their doctors to decide on the best treatment. “More rigorous scientific research is required to aid such decisions,” he added. His study, however limited, will help push the science along.

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