FDA strengthens Paxil's pregnancy warning.(News)

The Food and Drug Administration has stepped up warnings that paroxetine increases the risk of congenital defects, especially cardiovascular malformations.

In September, GlaxoSmithKline, which markets paroxetine under the trade name Paxil, had updated the drug's labeling in conjunction with the FDA. The change was based on initial data from a U.S. insurance claims database indicating a slightly higher risk of fetal defects in women who had taken the drug in the first trimester.

When further information became available in December, GlaxoSmithKline and the FDA agreed the label should be changed again, and that paroxetine should be reclassified from a pregnancy category C to a D. The D designation indicates "that studies in pregnant women have demonstrated a risk to the fetus," the agency said in a statement.

The warnings apply to all formulations of paroxetine, branded and generic.

Dr. Gideon Koren, director of the Toronto-based Motherisk program, expressed concern that the FDA's newest warnings will drive many pregnant women away from antidepressants. Treating depression during pregnancy should be a top priority, said Dr. Koren, whose program conducts research and serves as a clearinghouse on potentially toxic exposures and also counsels pregnant women.

GlaxoSmithKline said about 25% of prescriptions for paroxetine (including generics) are written for women of childbearing age.

Overall, analyses of data from two registries--one in the United States and one in Sweden--showed that women who take paroxetine during the first 3 months of pregnancy are 1.5-2 times more likely to have a baby with a heart defect than women who took other antidepressants, or women in the general population. According to the FDA, infants who were exposed to paroxetine in the first trimester had a 1.5-fold increased risk for cardiac malformations, and a 1.8-fold increased risk for congenital malformations of any kind, compared with infants exposed to any other antidepressant.