If the United States were a coal mine, the rising number of people suffering from depression would be the canary warning of increasing danger.

The U.S. Centers for Disease Control and Prevention’s National Center for Health Statistics reported last spring that the frequency of depression in adolescents and adults rose 60% over the past decade.

Many pregnant women are among that growing group. By one estimate, depression will burden 14% to 23% of women during their pregnancies. It is important that they receive treatment, not only for themselves but for the health of their babies. As the Society for Maternal-Fetal Health Medicine recently put it, “Untreated or undertreated depression during pregnancy carries health risks, such as suicide, preterm birth, preeclampsia, and low birth weight.”

About 8% of pregnant women receive treatment with a class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs). These drugs block the reabsorption of the neurotransmitter serotonin. That blockage makes serotonin more available to support communication between neurons in key regions of the brain. This, in turn, can help to relieve symptoms of depression.

SSRIs don’t banish depression, but studies show they can help to relieve it. Some people question the safety of prescribing antidepressants for pregnant women.

These skeptics got a boost late last month when the new U.S. Commissioner of Food and Drugs, Dr. Martin Makary, convened an “Expert Panel on SSRIs and Pregnancy.” Most of the panel members raised questions about the dangers for pregnant women who take SSRIs and their children. In their view, the risks include miscarriage and heart defects, autism spectrum disorder and other problems.

The National Curriculum for Reproductive Psychiatry issued a statement after the panel session that strongly disagreed with and refuted many of these claims and reiterated the importance of SSRIs as one important tool for treating depression in pregnant women.

To learn more about this debate, we spoke with Dr. Sarah Nagle-Yang, an associate professor at the University of Colorado School of Medicine on the Anschutz Medical Campus. Nagle-Yang is also the psychiatry department’s vice chair for quality, executive director of Colorado Women’s Behavioral Health and Wellness, and co-chair of the National Curriculum for Reproductive Psychiatry.

What does research tell us about the use of antidepressant medications during pregnancy?

There are limitations to the data gathered on the subject, Nagle-Yang said. The biggest obstacle: pregnant women have historically been excluded from randomized controlled studies of all medications. That means there are no head-to-head comparisons between women who take antidepressants during pregnancy and those who don’t.

Even so, Nagle-Yang said there’s plenty of evidence that antidepressants are safe during pregnancy.

“I do feel confident to say that these are some of the most extensively studied medications in pregnancy.”

The statement by the National Curriculum in Reproductive Psychiatry that followed the FDA’s “expert panel” discussion on antidepressants and pregnancy affirmed Nagle-Yang’s views.

What are the conclusions of the research about the use of antidepressants during pregnancy?

“There is a clear and robust consensus” from the American College of Obstetrics and Gynecology and other scientific organizations that antidepressant medications can be an important part of the overall plan of care to treat pregnant women who are diagnosed with anxiety and depression, Nagle-Yang said.

“When they are clinically indicated, the benefits of SSRI treatment outweigh the low risk associated with these medications,” Nagle-Yang said.

How have these antidepressant medications been studied? 

Researchers have relied on observational studies of what happens to women during their pregnancies in real time or retrospective studies that attempt to look back and analyze what happened to the women and their children during and after pregnancy, Nagle-Yang said.

These kinds of studies can yield valuable information, she said. But they can’t fully control for the many factors that may affect a pregnancy, such as the severity of a patient’s depression; other complications, like gestational diabetes; smoking; or patients who stopped taking their medications partway through pregnancy.

What are the evidence-based risks of taking antidepressants during pregnancy?

The medical literature shows that about one-third of women who take antidepressants during the second half of their pregnancies show symptoms of a condition called neonatal adaptation syndrome.

“What that sometimes looks like is babies that are more reactive than others or maybe have a harder time soothing or initiating feeding,” Nagle-Yang said. “Typically this lasts a couple of days or a couple of weeks.”

In those cases, mothers and their babies don’t need any particular treatment other than good care, she added.

Another question is whether taking antidepressants during pregnancy increases the risk of persistent pulmonary hypertension of the newborn, or PPHN. It’s a serious condition that restricts the flow of blood to the baby’s lungs.

Nagle-Yang said the most recent research shows there “may be” a modest increased risk — about 1.5 times — from the average for all pregnant women, which is about one to three live births per 1,000. Even with that increase in risk, PPHN is still “a very rare condition,” Nagle-Yang said.

She emphasized that she always discusses the risks of taking SSRIs with her patients. However, she also talks with them about the risks of not treating or undertreating their depression.

Are there studies that analyze the impacts on children who were exposed to antidepressants in utero?

Yes. A large recent study reported in JAMA Internal Medicine found that children whose mothers took antidepressants during pregnancy were not at risk for issues that surfaced later such as autism spectrum disorder, learning disabilities or attention-deficit/hyperactivity disorder.

Another study pointed to differences in regions of the brain that help to regulate emotions among children who were exposed to SSRIs before birth. Nagle-Yang called the study “well-conducted” and said it called for additional research.

She noted, however, that “a key limitation is that we don’t know how women who continued SSRIs during pregnancy differed from those who stopped.” Researchers also need more information about the severity of a patient’s mental illness and other conditions that might influence their child’s brain development.

Another crucial point is that changes in the brain structure won’t necessarily affect a child’s social or emotional development, Nagle-Yang said.

“While both SSRIs and untreated depression likely influence fetal brain development, current evidence – though imperfect – doesn’t suggest that SSRI exposure leads to consistent or lasting differences in developmental outcomes, like motor, language, cognition or emotional functioning, across studies and timepoints,” she said.

Some critics say that the symptoms of depression subside in many cases within five or six weeks. If that is true, would limited use of antidepressants during pregnancy make sense?

No. “The reality is that depression often does not resolve quickly on its own,” Nagle-Yang said. “The best available evidence suggests that only about 10% to 15% of depression cases (subside) spontaneously within three months without treatment.”

A far greater concern is that untreated depression increases the risk of poor pregnancy outcomes and chronic mental health issues, Nagle-Yang said.

“That’s particularly concerning during pregnancy, when both the parent and baby’s well-being are at stake.”

What are the risks of untreated depression and other mental health disorders during pregnancy?

Beginning with menstruation and continuing through menopause, women experience depression that is linked to fluctuations in reproductive hormones, Nagle-Yang said. These hormones, which are steroids that bind to receptors in the brain, directly affect mood.

“The data tell us that there is a subset of women who are especially vulnerable to fluctuations in these reproductive hormones,” Nagle-Yang said. The most dramatic fluctuations occur during the postpartum period, a high-risk time that increases the danger of debilitating depression, negative behaviors like substance use, and suicide.

“The biggest risk factor for postpartum depression is untreated depression during pregnancy,” Nagle-Yang said.

She added that women experiencing depression during pregnancy may find it difficult to keep themselves and their unborn babies healthy with good nutrition and exercise.

“The good news is that if you get treatment for your depression during pregnancy, it puts you in a good place going into the postpartum period,” Nagle-Yang said. “It’s the biggest thing you can do if you are someone with depression.”

Can untreated depression affect newborns?

Yes. “Your body is affected by your depression and anxiety,” Nagle-Yang said. “We see that in increased rates of preterm births and low birth weights among individuals with depression during pregnancy.”

Are some antidepressants safer or riskier than others?

As a class, antidepressants are “pretty similar,” Nagle-Yang said. Sertraline (Zoloft) is generally considered the first-line treatment because it has a low transmission to breast milk.

Some studies have linked paroxetine (Paxil) to “a small but significant” risk of cardiovascular defects in babies exposed to the drug during the first trimester of pregnancy, she said.

“If someone is on paroxetine and thinking about pregnancy, it’s a discussion to have,” Nagle-Yang said. “It’s not a complete contraindication, but it is a different conversation than with other SSRIs.”

Are there other strategies for a woman who doesn’t want to take medications but would like help with depression?

Yes. It’s never an “either-or” proposition to take antidepressant medications or not, Nagle-Yang said. Women may decide, after speaking with their doctors, that they don’t want or need medications to address their depression. There are other options to relieve symptoms, including psychotherapy, physical activity and connections with friends, family and coworkers, she said.

These steps can also help to improve sleep, which is another important part of relieving symptoms of depression, Nagle-Yang said.

Is it okay to stop using antidepressants during pregnancy?

It can be safe to stop using antidepressants during pregnancy, but it’s best not to stop taking the medications abruptly, Nagle-Yang said. People who stop taking SSRIs suddenly are at risk for antidepressant discontinuation syndrome, which can cause flu-like symptoms, nausea, insomnia and other issues. A patient who wants to come off the medications should work with their provider to taper their use gradually, she said.

Ultimately, the decision on medications is personal for each patient and dependent on multiple factors, including how severe their depression is and the factors that protect their emotional wellness, such as a strong support system and access to other therapies, Nagle-Yang said.

“I fully support people thinking through that with their treatment provider,” Nagle-Yang said.

She cautioned, however, that she rarely recommends that women with moderate to severe depression discontinue taking their medications, particularly with the added risk of postpartum depression looming.

What can the medical profession do to improve understanding of the benefits and risks of SSRIs to treat depression in pregnant women?

The National Curriculum in Reproductive Planning has helped to amass considerable information and education to help providers identify and treat psychiatric disorders in pregnant women, Nagle-Yang said.

“Yet this education has not been systematically included in the training of general psychiatry,” she noted. “That is part of what this organization is trying to address, because we think that every psychiatrist should be able to take care of women across their lifespan.”

The Accreditation Council for Graduate Medical Education does not recognize reproductive psychiatry as a subspecialty, Nagle-Yang said. However, as of November 2022, there were 16 psychiatry fellowship programs focused on women’s mental health and/or reproductive psychiatry.

In addition, the Department of Psychiatry at the University of Colorado School of Medicine now offers a one-year fellowship in reproductive psychiatry.

“I think we are slowly but surely building more capacity for training programs around the country,” Nagle-Yang said.

What expert advice about taking antidepressants would you give to women who are pregnant or considering becoming pregnant?

Nagle-Yang reiterated that studies of the safety and effectiveness of SSRIs during pregnancy are extensive and added that women should consider their mental and physical health inextricably linked.

“We would never say to someone with hypothyroidism, ‘don’t take your thyroid medication’ during pregnancy. They have an illness and need treatment,” she said. “We understand that that would not be in the best interest of the pregnancy. I think SSRIs are very much the same way.”