The risk of children developing heart defects due to maternal antidepressant use in the first trimester may be lower than originally thought, according to a study published June 18 in the New England Journal of Medicine. These findings challenge the FDA’s decision to classify selective serotonin-reuptake inhibitors (SSRIs) as Category D medications (evidence of human fetal risk, but benefits may warrant use) in pregnancy.
Krista F. Huybrechts, PhD, of the pharmacoepidemiology and pharmacoeconomics division at Brigham and Women’s Hospital in Boston, and colleagues reviewed the cases of 949,504 women with clinical depression enrolled in Medicaid from 2000 through 2007. The cohort taking an antidepressant was 6.8 percent.
A further breakdown of that number revealed that 4.9 percent were exposed to SSRIs, 0.7 percent to tricyclic antidepressants, 0.7 percent to serotonin-norepinephrine reuptake inhibitors, 0.9 percent to buproprion and 0.7 percent to other antidepressants. Most frequent SSRI’s prescribed were sertraline, paroxetine and fluoxetine, in that order.
Cardiac malformations were seen in 580 infants exposed to antidepressants in the first trimester as opposed to 6,403 infants who were not exposed. While propensity score adjusted risks for cardiac malformation was 1.06 among women with exposure to SSRIs, the research team found no significant associations between paroxetine and right ventricular outflow tract obstruction or sertraline and ventricular septal defect.
Huybrechts et al stated that not only do their results not support earlier findings on antidepressant use and cardiac anomalies, but their analyses also adjust the cohort to women with depression. They attempted to mitigate confounding factors that might increase the risk of malformations, risk factors that are more prevalent in a depressed population, such as smoking, drug and/or alcohol use and chronic conditions such as obesity or diabetes.
Because women with depression and anxiety were more likely to be followed medically from the start, Huybrechts et al noted that they are also more likely to utilize resources such as ultrasonography, amniocentesis and echocardiography of the infant, than nondepressed, healthy mothers. “Hence, there is a higher chance that a cardiac malformation might be detected in an infant that might otherwise have been undetected clinically, particularly milder defects such as muscular ventricular septal defects, which often close during early childhood,” they said.
They went on to emphasize that their findings did not support the idea that cardiac defects were more likely with antidepressant use and would recommend clinicians consider options when treating severe depression in women of childbearing age.