FDA Expert Panel Debates SSRI Safety During Pregnancy Amid Calls for Stronger Warnings

An FDA expert panel convened to address one of the most contentious issues in maternal healthcare: the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. The panel brought together perinatal psychiatrists, developmental biologists, epidemiologists, and obstetricians to evaluate current evidence on SSRI (search)Search drug safety and efficacy in pregnant women.

FDA Commissioner Martin Makary, MD, MPH, opened the session by acknowledging that "nearly 1 in 4 middle-aged women are on an antidepressant, and up to 5% of women in pregnancy are on an antidepressant." He noted that SSRIs "can be an effective treatment for depression," but cautioned that "serotonin may play a crucial role in the development of organs of a baby in utero," including the heart, brain and gut.

Evidence of Fetal Risks

Several panel members presented concerning data about SSRI (search)Search drug exposure during pregnancy. Anick Bérard, PhD, professor of perinatal epidemiology at the University of Montreal, reported that SSRIs during pregnancy have been tied to "a higher risk for spontaneous abortion, congenital malformations, prematurity, low birth weight and ADHD (search)Search disease or autism, with an increased risk ranging from 10% to 87%, depending on the adverse pregnancy outcome."

Jay Gingrich, MD, PhD, director of the Institute for Developmental Sciences at Columbia University Irving Medical Center, presented findings from large-scale studies linking in utero SSRI (search)Search drug exposure to increased rates of adolescent depression. "Until recently, there's really never been any attempt to study whether this treatment of the mother actually improves outcomes in the offspring," he noted.

Adam Urato, MD, chief of maternal-fetal medicine at MetroWest Medical Center, emphasized that there is "widespread scientific agreement" that SSRIs influence fetal brain development. Long-term studies have shown higher rates of speech and language difficulties in addition to autism and depression in exposed children.

"If serotonin plays a crucial role in the fetal development, and it does, and if the SSRIs cross the placenta and disrupt the serotonin system, which they do, then the SSRIs must disrupt fetal development," Urato said, citing human and animal studies showing "that SSRIs impact individual neurons in the developing brain."

Calls for Enhanced Warning Labels

Multiple experts criticized current FDA labeling as inadequate. Urato noted that "patients regularly tell me that essentially the only counseling they received is that SSRIs don't affect the baby or cause complications. This is simply not accurate or adequate, but this is essentially what you could conclude based on the current FDA labels for these drugs."

He pointed out that there is currently no warning for preeclampsia or preterm birth, and "the postpartum hemorrhage warning needs to be strengthened, but perhaps the major shortcoming is the label doesn't make clear that SSRIs alter fetal brain development."

Josef Witt-Doerring, MD, a psychiatrist at Taperclinic and former FDA medical officer, highlighted inconsistencies in drug labeling within the same class. "LexaproView drug details may harm the unborn baby in one medication guide, [but] ZoloftView drug details does not emphasize that — it emphasizes withdrawal," he said. "It doesn't make sense that we should have inconsistent medication guide labeling."

Risks of Untreated Depression

Mental health advocates presented a counterargument emphasizing the dangers of untreated perinatal depression. Kay Roussos-Ross, MD, professor and director of the perinatal mood disorders program at the University of Florida College of Medicine, stated that "treating mental illness is not a luxury, it is a necessity."

According to Roussos-Ross, perinatal mood disorders affect 20% of pregnant people in the U.S. "Despite this prevalence, at least half of affected women go untreated or undertreated during their pregnancy and postpartum," she said.

The risks of untreated depression include preterm delivery, small for gestational age babies, and inadequate bonding and attachment. "When mental health conditions go untreated, these women are less likely to attend their prenatal care appointments and are more likely to use substances during their pregnancy," Roussos-Ross explained. "They are also more likely to face additional risks such as preeclampsia and cesarean delivery."

Tiffany A. Moore Simas, MD, MPH, MEd, MHCM, a professor at the University of Massachusetts Chan Medical School, told Healio that "the risks of untreated perinatal mental health conditions, which in addition to having significant negative consequences for pregnant persons, offspring and families, are the leading cause of overall and preventable maternal mortality via suicide and overdose."

Questioning SSRI Efficacy

Some panel members challenged the fundamental premise of SSRI (search)Search drug effectiveness. Joanna Moncrieff, MD, professor of Critical and Social Psychiatry at University College London, stated, "There is very little evidence that antidepressants have actual benefits in depression."

Jeffrey Lacasse, PhD, MSW, associate professor at Florida State University's College of Social Work, noted that "88% of Americans believe that antidepressants correct chemical imbalances, despite no conclusive scientific basis." He suggested this belief contributes to overprescribing among women of reproductive age.

Biological Mechanisms of Concern

Michael Levin, PhD, distinguished professor at Tufts University, provided evidence that serotonin signaling plays a critical role in early embryonic patterning and organ asymmetry. "Manipulating its use by cells with SSRIs is very, very likely to cause certain kinds of defects," he said, referencing experiments in frogs and chicks.

Need for Shared Decision-Making

Panel members repeatedly emphasized the importance of informed decision-making between pregnant patients and healthcare providers. "The importance of informed decision-making in pregnant women is essential," Bérard said. "Pregnant women will be the ones making the decision, and they will be acknowledging the risks and benefits for themselves if it is well explained to them."

Moore Simas emphasized that discussions about treatment risks "must be balanced with information about not treating. The evidence on balance supports treatment, especially given early data have many limitations, including use of inappropriate comparison groups."

The FDA has not yet announced whether it will revise current SSRI (search)Search drug labeling or issue new guidance, but indicated it would consider the panel's input in evaluating potential policy updates.