The Food and Drug Administration warned pregnant women and their doctors away from the antidepressant Paxil yesterday because of an increased risk of heart defects in newborns.
With the warning, the agency for the first time placed a popular antidepressant -- one in the same drug class as Prozac and Zoloft -- into its second-highest category for risk of birth defects. The agency did not say Paxil could never be used by pregnant women, but it did say the FDA "is advising patients that this drug should usually not be taken during pregnancy."
The advisory is based on early results from two studies, which found that women who took Paxil in the first three months of pregnancy were 11/2 to two times more likely to give birth to a child with a heart defect than women who took other antidepressants or pregnant women overall. The studies found that Paxil had a risk of birth defects that other common antidepressants did not.
"If you're on Paxil and pregnant, our advice is to talk to your physician and consider switching to a different drug," said Robert Temple, the FDA's director of medical policy. "Abrupt withdrawal of Paxil has its own problems, but the clear suggestion here is that you might want to think about a change."
In the studies cited by the FDA, the risk of heart defects is about 1 percent overall and rose to 1.5 to 2 percent in infants born to women taking Paxil.
Although researchers have been concerned for some time about the effect of selective serotonin reuptake inhibitors (SSRIs) on fetuses, yesterday's announcement by the FDA and Paxil manufacturer GlaxoSmithKline is the strongest indication so far that there may be significant risks. Since a large number of pregnant women suffer some form of depression -- some estimates are as high as 20 percent -- decisions about whether to start or continue on antidepressants are increasingly common and difficult.
Adding to the complexity of the decision, an earlier study published in the Journal of the American Medical Association found that the babies of mothers taking antidepressants were three times more likely to suffer from irritability, tremors and seizures in the weeks after birth. With so many concerns, support groups for pregnant women on antidepressants are now widespread.
Yesterday's advisory was based largely on a new analysis of data from Sweden's birth registry, which collects information on pregnant women and their offspring. An initial analysis of that large database found no correlation between birth defects and use of SSRIs, but a follow-up study found that birth defects were twice as common among Paxil users as among women taking other antidepressants or none at all.
Most birth defects associated with antidepressants involve holes and malformations in the chambers of the heart. The defects often heal on their own, and more severe cases can be surgically repaired. Glaxo spokeswoman Gaile Renegar said the company is studying how and why its drug might be causing these defects, adding that it remains unclear whether there is a cause-and-effect relationship.
Kimberly Yonkers, a psychiatrist at the Yale School of Medicine who studies the treatment of mood disorders among pregnant women, cautioned that the database studies the FDA had used had limitations: Unlike controlled studies, Paxil may have been prescribed far more than other drugs, skewing the results. Also, she said, databases sometimes concealed unrelated medical problems that could alter outcomes.
"Depression is still undertreated," she said. "Pregnant women in particular are immensely undertreated, and you worry about people being unduly frightened."
Paxil is one of the world's most popular antidepressants, taken by tens of millions of patients since the drug was approved in 1993. It is also sold now in generic form as paroxetine. Renegar said yesterday that about 25 percent of Paxil users are women of childbearing age, between 18 and 45.
American regulatory officials have generally been slower to issue warnings about antidepressants than their counterparts in other countries, especially in Britain and Canada.
Officials here have repeatedly argued that the risks of antidepressants need to be balanced against their benefits. Many of the drugs, including Paxil, have been shown to be effective against depression, anxiety and other psychiatric disorders, especially among adults. No hard studies prove antidepressants lower the risk of suicide, but many experts believe that to be the case, and trace a lowered suicide rate in the United States to the increased use of antidepressants such as Paxil.
In its warning yesterday, the FDA acknowledged this trade-off. "In individual cases, the benefits of continuing paroxetine may outweigh the potential risk to the fetus," FDA officials said. However, they added, in general, Paxil "should generally not be initiated in women who are in their first trimester of pregnancy or in women who plan to become pregnant in the near future."