The FDA and drug company GlaxoSmithKline have strengthened their warning about using the antidepressant drug Paxil during early pregnancy.

The warning is based on early results from two studies. The studies showed a higher rate of heart-related birth defects in babies born to women who took Paxil during early pregnancy than in babies of women in the general population or women who took other antidepressants.

The first of those studies prompted an FDA alert and an updated drug label by GlaxoSmithKline, which makes Paxil, in September.

Now, results of the second study have prompted an update. The update includes moving Paxil to a category “D” medication instead of a category “C” for use during pregnancy.

That change reflects a stronger warning about use during early pregnancy. Category “D” drugs have shown risks to fetuses in studies of pregnant women. However in this category, the benefits of the therapy may outweigh the risks.

GlaxoSmithKline, a WebMD sponsor, is sending a letter to doctors with the updated information.

More Heart-Related Birth Defects

In both studies, heart-related birth defects were rare but more common among women who took Paxil in early pregnancy.

“The expectation is that in the general population, the risk of cardiovascular defects is about one per 100 infants,” GlaxoSmithKline spokeswoman Gaile Renegar tells WebMD.

She says the studies show a risk of those heart-related birth defects is one per 50 babies born to women who used Paxil in early pregnancy.

Cause Not Clear

The studies didn’t assign anyone to take Paxil and don’t necessarily prove that Paxil caused those birth defects.

“It’s not clear whether there’s a true causal association,” Renegar says.

Most of the heart defects reported in these studies were holes in the walls of the chambers of the heart (atrial and ventricular septal defects).

“In general,” states the FDA, “these types of defects range in severity from those that are minor and may resolve without treatment to those that cause serious symptoms and may need to be repaired surgically."

Studies’ Results

According to the FDA, early results from the two studies showed that women who took Paxil during the first three months of pregnancy were about 1.5 to two times as likely to have a baby with a heart defect as women who received other antidepressants or women in the general population.

In one study, the risk of heart defects in babies whose mothers had taken Paxil early in pregnancy was about 2 percent, compared with a 1 percent risk in the whole population.

In the other study, the risk of heart defects in babies whose mothers had taken Paxil in the first three months of pregnancy was 1.5 percent, compared with 1 percent in babies whose mothers had taken other antidepressants in the first three months of pregnancy.

Weighing Risks and Benefits

The FDA’s news release notes that “the benefits of therapy may outweigh the potential risks to the fetus.”

“In the labeling, I think there’s some important guidance for prescribers as well as patients to take note of,” Renegar says.

“The labeling now advises that patients who become pregnant while they’re taking [Paxil] should certainly be informed of the potential harm to the fetus,” she says.

“Consideration should be given to discontinuing [Paxil] or perhaps switching to another antidepressant, unless the benefit that the mother is experiencing justifies continuing treatment,” Renegar continues.

“For women who intend to become pregnant or are in their first trimester of pregnancy, other treatments and options should be considered first before initiating Paxil. So these are the recommendations that GSK and the FDA support to help put this information in a useful context for physicians as well as women to make well-informed treatment decisions,” she says.

Maker’s Comment

“These studies that are referenced in the new labeling are largely updated analyses from the data that was the justification for the change in September,” Renegar says.

“We have worked very closely with the FDA on the data interpretation, and what the labeling should say, and how to most quickly and effectively get this out into the public,” she says. “It was a collaborative effort.”

By Miranda Hitti, reviewed by Brunilda Nazario, MD

SOURCES: News release, FDA. WebMD Medical News: “Paxil’s Birth Defects Warning Strengthened.” Gaile Renegar, spokeswoman, GlaxoSmithKline. Letter, GlaxoSmithKline: “Dear Healthcare Professional.” Associated Press.