June 9, 2004 — An expert panel is urging better information for pregnant women who take popular antidepressant medications because of concerns that the drugs could cause adverse effects in newborns.

The FDA advisors say they have too little data to understand exactly how the drugs may be affecting newborn infants.

Regulators are concerned by reports suggesting that antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, may cause health effects in newborns when mothers take the drugs for depression late in pregnancy. The agency has received hundreds of preliminary reports of adverse effects in newborns over the last decade.

Experts stress that the reports are intended only to alert regulators to potential hazards and do not necessarily mean that a drug caused the effects. But the agency has received reports for all SSRIs on the market, including Prozac, Paxil, Luvox, Zoloft, and Celexa.

The reports suggest that infants whose mothers took the medications can experience drug withdrawal symptoms or toxicity after delivery. Effects are wide-ranging, though the most common include trouble eating, irritability, body rigidity, and respiratory trouble, says Kathleen Phelan, a safety evaluator in the FDA’s division of drug risk evaluation.

The agency has also recorded 19 adverse events in women who took Effexor, an antidepressant drug closely related to SSRIs, late in pregnancy. Those reports include incidents of seizures, jitteriness, and jaundice.

“All of the SSRIs have been associated with these adverse events,” says Robert Levin, MD, a reviewer in the FDA’s division of neuropharmacologic drug products.

An estimated 10% to 16% of all pregnant women suffer from depression, according to FDA data.

Reports prompted the FDA last month to alter labeling for the entire SSRI drug class, warning that some newborn infants exposed to SSRIs and Effexor have developed symptoms requiring prolonged hospitalizations, respiratory support, and tube feeding.

Zoloft maker Pfizer Inc. has not yet accepted the FDA’s label changes and remains in discussions with the agency, Levin says.

Stronger Labeling

The FDA is now moving to include more warnings to doctors and patients inside of drug packaging. The agency has not yet formulated the warnings, but officials suggested that they may urge physicians and patients to strongly weigh the benefits of antidepressant medications with the possible risks to the newborn baby.

“What we want them to do is realize there are things that happen to neonates when moms take these drugs that need to be considered,” says Katherine L. Wisner, MD, a professor of psychiatry and obstetrics at the University of Pittsburg and a member of the FDA pediatric drug advisory panel.

Experts say they are concerned over the lack of good studies on how to avoid newborn exposure or how best to treat depression during pregnancy. While some women can simply avoid taking the drugs in the third trimester of pregnancy, others could experience severe depression symptoms if they stop their medications.

“Depression itself can create negative outcomes,” Wisner says. Many doctors now have their pregnant patients slowly decrease the dose and stop their SSRI use before delivery in an attempt to ease medication withdrawal while minimizing fetal exposure, she says.

More Questions Than Answers?

Still, researchers don’t know whether infants with SSRI-associated symptoms are suffering from drug withdrawal after birth or whether the drug is having a direct toxic effect on the newborns’ systems. They also don’t have enough information on what effects the exposures could be having on the infants’ long-term health.

“We don’t know what these manifestations represent, and therefore we don’t know what to do about it,” says Joan P. Chesney, MD, director of academic programs at St. Jude’s Children’s Research Hospital in Memphis, Tenn., and the panel’s chairwoman. “We don’t really know what we’re looking for in the newborn.”