Women should be better informed about the potential risks of using selective serotonin reuptake inhibitors (SSRIs) during pregnancy, and these risks should be weighed against their benefits, most speakers on an FDA panel
selected by Commissioner Marty Makary, MD, MPH, agreed on Monday.
"Up to 5% of women in pregnancy are on an antidepressant. Antidepressants like SSRIs can be an effective treatment for depression," said Makary during his opening remarks, though he warned that SSRIs "may be unique" because of their potential interaction with pregnancy.
"Serotonin may play a crucial role in the development of organs of a baby in utero, specifically heart, brain, and even the gut," he continued. "SSRIs have also been implicated in different studies to be involved in postpartum hemorrhage, pulmonary hypertension, and cognitive downstream effects in the baby, as well as cardiac birth defects."
Some of the 10 panelists -- consisting of experts in psychology, psychiatry, and ob/gyn -- have spoken out against SSRIs for years, dismissed the entire class as "placebos," and published papers linking the drugs to autism and other conditions in offspring.
During Monday's discussion, some panelists suggested that the risks of prenatal SSRI use on offspring have flown under the radar for the past few decades. Others potential risks flagged in prior studies include possible behavioral-related risks, attention deficit-hyperactivity disorder (ADHD), depression, and anxiety.
None of these outcomes have been verified in randomized, placebo-controlled trials since pregnant women are typically excluded from such studies. Observational studies have suggested these outcomes, and some studies have reported conflicting findings. A few MRI studies in offspring exposed to SSRIs in utero have been conducted, one of which found an association with changes in brain regions involved in emotional regulation.
However, the absolute risk for many of these outcomes is low, said Kay Roussos-Ross, MD, of the University of Florida College of Medicine in Gainesville, with the exception of neonatal adaptation syndrome, which occurs in about 25% to 30% of babies exposed late in pregnancy. This can cause jitteriness, irritability, and respiratory distress in affected babies, but typically resolves within a few days to weeks.
Roussos-Ross was one of the few panelists to highlight the harms of untreated depression in mothers, which should be balanced against any potential risk of SSRI exposure in offspring, she said. "One of the leading causes of maternal death in the U.S. is mental health, including suicide and overdose deaths."
"Research shows that in women who stop their medications in pregnancy, they are five times more likely to experience a relapse in their mood symptoms compared to those who continued their medications during pregnancy," she noted.
Other adverse outcomes with untreated depression in pregnant women can include preterm delivery, cesarean delivery, small-for-gestational-age babies, a lower likelihood of attending prenatal care appointments, a higher likelihood of using substances during pregnancy, preeclampsia, and inadequate bonding and attachment difficulty with their children, she said.
Agreeing with Roussos-Ross, Jay Gingrich, MD, PhD, of Columbia University Irving Medical Center in New York City, said SSRIs shouldn't be withheld from pregnant women with depression, but women should be better informed of their risks.
"There needs to be a stronger warning in the warning section," added Adam Urato, MD, chief of maternal-fetal medicine at MetroWest Medical Center in Framingham, Massachusetts. He proposed adding a boxed warning to the label of all SSRIs, "so people realize the impact these chemicals ... have on the developing baby and pregnancy complications on mom, as well."
Former FDA official Josef Witt-Doerring, MD, who now runs a clinic that aims to help patients taper off psychiatric medications, raised concerns about inconsistent labeling across the SSRI class, citing the example of escitalopram (Lexapro) and sertraline (Zoloft), which currently tout different language on their labels to warn about potential harms to unborn babies.
He suggested the FDA get more creative in disseminating drug risk information. "If we could get QR codes with patient-friendly videos talking about the most important risks right on the bottle cap that says 'watch me,' we could do wonders," he said.
But David Healy, MD, a fellow of the Royal College of Psychiatrists, said the responsibility of educating patients about the risks should fall on the prescribing doctors, not the FDA. "Make doctors great again," he said.
Many of the panelists advocated for greater uptake of alternative treatment options for depression in pregnant women, including psychotherapy and other pharmacological options such as tricyclic antidepressants like nortriptyline and atypical antidepressants like bupropion.
A few panelists made controversial claims during Monday's discussion, including dismissing SSRIs altogether by questioning their efficacy. Joanna Moncrieff, MD, of University College London, said the benefits of antidepressants were "barely distinguishable from placebo."
Countless studies have shown the benefits of antidepressants, including a meta-analysis of 21 antidepressants, and a randomized trial that showed that adults on antidepressants for a prolonged period were significantly less likely to have a relapse of a depressive episode if they stayed on treatment.
Advocating against the "medicalization of the human experience," Roger McFillin, PsyD, executive director of the Center for Integrated Behavioral Health in Bethlehem, Pennsylvania, suggested that women naturally feel their emotions more than men, "which are gifts and not a symptom of disease," and shouldn't start on SSRIs to only "become dependent on the medical system."
In response to the meeting, Steven Fleischman, MD, MBA, president of the American College of Obstetricians and Gynecologists (ACOG), said that “unfortunately, the many outlandish and unfounded claims made by the panelists regarding SSRIs will only serve to incite fear and cause patients to come to false conclusions that could prevent them from getting the treatment they need.”
“Robust evidence has shown that SSRIs are safe in pregnancy and that most do not increase the risk of birth defects,” he noted.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.