In a common enough scenario, a pregnant patient being treated for depression or anxiety reads an article that links maternal antidepressant use during pregnancy with birth defects and wonders whether she should stop taking the medication.
Nearly 20% of women experience depression and anxiety during and after pregnancy1, and the use of antidepressants during pregnancy is rising. One study found the use of antidepressant medications during pregnancy increased from 5.7% in 1999 to 13.4% in 2003. Selective serotonin reuptake inhibitors (SSRIs) accounted for most of the antidepressants prescribed.2
Many other studies have looked at possible consequences ranging from birth defects, preterm delivery, neonatal syndromes, developmental effects, and even autism and attention deficit/hyperactivity disorder (ADHD). The results have spawned controversy and a long-running debate that has divided researchers into two groups. Some feel antidepressant medications should be considered as a beneficial treatment option for expectant women struggling with depression. Others consider these medications harmful based on evidence from animal models and human studies.
For more than 10 years, Adam Urato, MD, a maternal-fetal medicine obstetrician specializing in high-risk pregnancy at Tufts University School of Medicine, has been an outspoken critic of antidepressant use during pregnancy. He points to the basic science showing that serotonin plays a key role in the formation of organs as the embryo develops into a fetus.
Serotonin’s Influence on Embryos
“Serotonin is crucial in development,” Urato tells Psychiatry Advisor. “SSRI antidepressants [also] disrupt the serotonin system, and they freely cross the placenta. So what do we expect to see? We expect to see that animal studies will show harm, and they do.
“We see birth defects, we see pregnancy loss, and we see abnormalities in development of these rats and mice,” he continues. “Then when we [get to] the human studies, we see further evidence of harm and that evidence continues to grow.”
In a review of 41 studies, published earlier this year in PLoS ONE looking primarily at antidepressant use and risk of preterm delivery, Urato and colleagues found pooled risk odds ratio estimates ranging between 1.16 (95% CI 0.92–1.45) and 1.96 (95% CI 1.62–2.38). The associations were stronger for antidepressant use later in pregnancy. Adjusting for a diagnosis of depression in most cases did not eliminate the effect, although the strength of the observed associations was somewhat lessened.3
“Our review looked at 41 studies of preterm birth, and 39 of the 41 studies showed increased rates of preterm birth. This is not inconsistent. This is not 50/50,” says Urato.
However, Nancy Byatt, DO, MBA, FAPM, a perinatal psychiatrist at the University of Massachusetts Medical School, is among the experts who believe the medication is helpful. Supporters contend that the available data on harm from antidepressant exposure during pregnancy have been inconsistent. Proponents also maintain that it is difficult to tease out whether the harm stems from the medications or the depression itself.
To look at the available human studies, Byatt and colleagues conducted a comprehensive review of almost 160 studies on the risk of first trimester teratogenicity, postnatal adaptation syndrome (PNAS), and persistent pulmonary hypertension (PPHN) with in utero antidepressant exposure.