FDA Panel

FDA Panel Discusses Safety, Use of SSRIs During Pregnancy

Kate Young

In a wide-ranging discussion, an expert panel convened by the FDA reviewed current evidence and clinical practices surrounding the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. The panel included psychiatrists, maternal-fetal medicine specialists, neuroscientists, and policy experts, and centered on emerging data regarding fetal exposure to SSRIs, the burden of perinatal mood and anxiety disorders, and the adequacy of current FDA labeling.

Prevalence and Prescribing Context

Perinatal mood and anxiety disorders affect approximately 20% of pregnant individuals in the United States, with up to 6% prescribed antidepressants—primarily SSRIs—during pregnancy.1-5 Multiple panelists underscored the clinical importance of managing these conditions, citing their association with preterm birth, low birth weight, poor prenatal care engagement, and maternal suicide.6-8 Kay Roussos-Ross, MD, a perinatal psychiatrist and obstetrician who focuses on high-risk obstetric patients with co-morbid psychiatric and substance use disorders, emphasized that SSRIs are among the most studied psychiatric medications in pregnancy and noted that untreated depression carries its own well-documented risks.

However, several panelists warned that women often initiate SSRIs years before pregnancy, based on outdated or oversimplified explanations of depression as a “chemical imbalance.” Jeffrey Lacasse, PhD, MSW, associate professor of social work at Florida State University, presented survey data showing that nearly half of women of childbearing age were told by a provider that serotonin imbalance was the cause of their depression9—an idea no longer supported by current psychiatric consensus.10-12

Clinical Implications

  • Routine screening for depression and anxiety in pregnancy may be important, as perinatal mood disorders affect up to 20% of pregnant patients.
  • Given that SSRIs are often initiated years before conception, preconception counseling should include discussion of risks and withdrawal planning.
  • Providers should evaluate patients’ understanding of their diagnosis and treatment rationale, especially regarding outdated notions of “chemical imbalance.”

Prenatal Exposure: What the Data Indicate

Presenters reviewed both epidemiologic and preclinical data regarding potential harms of prenatal SSRI exposure. Some observational studies suggest a very modest increased risk of spontaneous abortion, preterm birth, neonatal adaptation syndrome, and neurodevelopmental disorders such as autism and language delay.13-17 Anick Bérard, PhD, professor of perinatal epidemiology at the University of Montreal, noted, for example, that an 87% increased relative risk of autism translates to a rise in absolute risk from 1% to 2%.18

Animal and imaging studies suggest biologically plausible mechanisms. Jay Gingrich, MD, PhD, and Michael Levin, PhD, reviewed evidence that SSRIs administered during gestation alter fetal brain development in rodents and humans. Dr Gingrich’s research in large Finnish and American cohorts found increased adolescent depression in children exposed to SSRIs in utero,19 while Dr Levin demonstrated serotonin’s role in early embryonic patterning, including left-right organ development.20

Adam Urato, MD, a maternal-fetal medicine physician, emphasized that SSRIs are known to cross the placenta and impact fetal physiology, including platelet function and serotonin signaling.21-22 He and others called for updated FDA warnings highlighting these effects.

The timing of exposure may also influence fetal risk, as multiple panelists noted that the risk-benefit calculus differs between the first trimester — when organogenesis and miscarriage risk are key concerns — and later trimesters — where preterm birth and neurobehavioral impacts may predominate.23-24

Clinical Implications

  • SSRIs cross the placenta and are biologically active in the fetal brain, with observational and imaging studies suggesting neurodevelopmental impact.
  • Absolute risk increases for outcomes like autism or spontaneous abortion are small and must be clearly communicated in shared decision-making.
  • MRI and animal model data indicate trimester and timing may matter, suggesting a potential need for trimester-specific risk discussions.

Debate Over Benefit and Informed Consent

Opinions diverged sharply on the net benefit of SSRIs in pregnancy. Some speakers, including Joanna Moncrieff, MD, professor of critical and social psychiatry at University College London, questioned whether SSRIs offer significant benefit at all, citing meta-analyses showing minimal advantage compared with placebo in randomized trials.25-26 Psychiatrist Josef Witt-Doerring, MD, said that many of his patients are unaware of both the limited efficacy and potential withdrawal challenges when attempting to taper antidepressants in preparation for pregnancy.

Dr. Roussos-Ross and others argued that for some women—especially those with moderate-to-severe depression—SSRIs are a vital treatment option that can be safely continued through pregnancy. She noted that relapse rates are higher in women who discontinue antidepressants,27-28 and that confounding variables (e.g., socioeconomic status, comorbid substance use) complicate causal attribution in studies linking SSRIs to adverse outcomes.29

Both sides agreed, however, that clinicians must provide comprehensive, individualized counseling and support shared decision-making. Dr Bérard advocated for more personalized risk assessments based on trimester, symptom severity, and comorbid conditions. Multiple panelists highlighted that many primary care and obstetric providers face severe time constraints—often just minutes per patient visit—which can hinder meaningful risk-benefit discussions. Panelists also called for improvements in how risk information is conveyed—suggesting QR codes on pill bottles, revised medication guides, and more consistent labeling across SSRIs.

Clinical Implications

  • Clinicians must distinguish between mild, moderate, and severe depression to appropriately match treatment intensity, including medication versus non-pharmacologic options.
  • Informing patients about the relative efficacy of SSRIs and potential for neonatal adaptation syndrome may help promote ethical prescribing.
  • Time constraints in primary care may limit adequate risk-benefit counseling, suggesting a need for system-level tools (e.g., decision aids, medical guide enhancements).

Calls for Systemic Change

Underlying the clinical discussion were broader critiques of pharmaceutical marketing, prescribing culture, and systemic time constraints in primary care. Several panelists, including psychologists and withdrawal specialists, argued that SSRIs are overprescribed for mild distress and that nonpharmacologic treatments like psychotherapy are underutilized due to cost and access barriers.

Panel moderators and FDA officials concluded by acknowledging the complexity of the issue and the need for additional data—particularly from randomized trials and mechanistic studies. While SSRIs remain an essential option in perinatal care, the panelists broadly agreed that clearer communication, stronger warnings, and a more holistic approach to maternal mental health are urgently needed.

Clinical Implications

  • Providers should proactively initiate preconception discussions with patients of reproductive age who are prescribed SSRIs, even if pregnancy is not immediately planned.
  • Improved interprofessional coordination (e.g., between OB/GYNs, psychiatrists, and primary care) can enhance preconception and prenatal care quality.
  • Expanding access to psychotherapy, social support, and other evidence-based treatments can help ensure that patients have a full range of options tailored to the severity of their symptoms and individual needs.

 

References:

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