With Paxil an FDA Category D, will other Antidepressants Follow?

Washington, DCAs many continue to hope for an announcement from the US Food and Drug Administration (FDA) with regard to drugs categorized as Category "D", the question looms as to whether any antidepressants will ultimately garner the category "D" label. Given the inclusion of Paxil in that category currently, and its association with Paxil birth defects, what other SSRIs might follow?

Paxil (paroxetine) didn't start out as a Category "D" drug. The antidepressant was originally a Category "C," which is a class that suggests less risk for pregnant women and their unborn children. However, that all changed in December 2005 when Paxil was reclassified by the FDA to the more cautionary Category "D," given that studies had shown a risk to the fetus.

"FDA has determined that exposure to paroxetine in the first trimester of pregnancy may increase the risk for congenital malformations, particularly cardiac malformations," stated an advisory to health care professionals at the time.

There are various Paxil side effects that remain a concern to all patients who take the antidepressant. However, concern over Paxil birth defects are worrisome—especially in light of test results made available as part of the discovery for a Paxil lawsuit that was heard in 2009.

To that end, the results of studies conducted by the originator of Paxil on lab rats and rabbits in 1979 and 1980 have, prior to the trial, been under seal and not available to either the FDA or the US Congress but known to GlaxoSmithKline—the current manufacturer of Paxil.

A UK-based expert on teratogenicity testified for the plaintiffs on the results of one study addressing the potential for teratogenicity, which was explained as an agent with the potential to cause birth defects. The agent, explained Dr. David Healy, could be a drug, a virus or an illness.

Of the studies described in court, one was the most compelling. The latter involved three groups of pregnant rats given Paxil at doses of 5, 15 and 50 milligrams. Pregnancy outcomes at birth and four days beyond were compared to rats born to mothers having received no Paxil at all.

The studies helped to explain the potential for Paxil birth defects.

Rat pups born to mothers who did not receive Paxil were all born alive. Of the 415 pups born to mothers given Paxil, 47 pups were born dead.

In the 5-milligram exposure group, 65 percent were dead by day four. Ninety-two percent of pups born from the 15-milligram group had died by the fourth day.

Of the pups exposed to 50 milligrams, 100 percent were dead by day 4.

While it is rare, Paxil birth defects and Paxil heart defects have been alleged to be associated with the use of the Paxil antidepressant by pregnant women—an allegation that has been the basis of many a Paxil lawsuit.

The pending announcement by the FDA with regard to Category "D" drugs would be of great interest to those monitoring all antidepressant drugs--and SSRIs in partcular--to see 'who's next?' for the Category "D" label.