New Warning Issued on Paxil
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U.S. health officials have issued a warning about possible birth defects in infants born to women who take the antidepressant Paxil during the first trimester of pregnancy.
A study sponsored by GlaxoSmithKline, the drug’s maker, suggested that infants born to women taking Paxil were at about double the risk of birth defects compared with women taking other antidepressants. The most common defects were cardiovascular. The risks were about 50 percent higher than they were in the general population.
GlaxoSmithKline, which first alerted the U.S. Food and Drug Administration of the problems around Sept. 6, anticipates labeling changes to the drug, said company spokeswoman Mary Ann Rhyne.
“We’ve also taken this information to regulatory bodies around the world to voluntarily add this to the label,” she said. “That discussion, as I understand it, is how to handle it.”
Glaxo has also sent a letter to physicians alerting them to the findings.
Dr. Mary Jo O’Sullivan, a professor of obstetrics and gynecology at the University of Miami School of Medicine, said the findings do raise some concerns. “One cannot deny with absolute certainty that there’s nothing related to Paxil and an increased risk of malformations, but we dont have a truly controlled population,” she said.
“One has to be cautious and if there’s a way to get a patient off Paxil prior to pregnancy and substitute another drug, then that would be the ideal way to go,” O’Sullivan advised. “But just because she’s on Paxil does not necessarily mean that her risk of congenital malformation is overwhelming. This needs more work.”
Paxil (paroxetine) belongs to a group of drugs called selective serotonin reuptake inhibitors (SSRIs), which first hit the market in 1988 and are widely used today to treat depression, anxiety and other mood and behavioral disorders in adults as well as children.
This class of popular drugs has been the subject of much recent controversy.
In February, Spanish researchers reported that babies born to women taking SSRIs during pregnancy may experience neonatal withdrawal syndrome in the first few days of life. The association seemed to be highest among women using Paxil.
And last year, reports of suicidal thinking among adolescents using SSRIs led to the FDA ordering a “black box” warning be placed on SSRI labels. There has also been concern that SSRIs triggers manic behavior in 10- to 14-year-olds.
The data on SSRIs and birth defects is inconclusive, with some studies showing a higher risk and other research showing no increased problem.
GlaxoSmithKline undertook this study because a British pregnancy registry turned up a possible signal for cardiovascular defects in women using bupropion (Wellbutrin) and Paxil.
For this study, the researchers relied on a database affiliated with UnitedHealthcare, a national managed-care plan covering the Northeast, Southeast, Midwest and Western United States. They focused on women taking bupropion in the first trimester of pregnancy and compared them with infants born to women who took bupropion before or after the first trimester, as well as women taking other antidepressants during the first trimester.
When all analyses were completed, there appeared to be no increased risk associated with bupropion. A secondary analysis to investigate the risk associated with other antidepressants, including Paxil, was carried out at the request of the FDA.
That analysis found about double the risk of general birth defects in Paxil compared to other antidepressants, when taken in the first trimester. The prevalence of birth defects as a whole among infants born to women in this group was 4 percent, or 43.6 per 1,000 births.
The risk for cardiovascular defects was slightly more than double. The more common of these were ventricular septal defects, where one or more holes are present in the muscular wall separating the right and left ventricles of the heart. This is the most common congenital heart defect.
The overall rate of birth defects in the general population is about 3 percent, and the rate of heart defects about 1 percent. The overall rate among infants of women taking Paxil in the first trimester was about 4 percent and, for women taking other antidepressants during this time, about 2 percent. “I wished I had an explanation,” Rhyne said of the discrepancy.
Researchers still do not know if the relationship is a causal one and there is, in general, a paucity of research on the subject. Data from the Swedish Birth Registry, for instance, found no increased risk of major malformations associated with SSRIs. But other small studies have found risks.
“There’s not a whole lot of detail there,” Rhyne said. “We’re trying to drill down on information that we have to see exactly what is going on.”
And for women who are on Paxil or considering taking it, GlaxoSmithKline said it is sticking by previous recommendations.
“This medicine already has a pregnancy precaution. That means that physicians should be talking with patients about potential benefits and potential risks and we recommend that this study be a part of that discussion,” Rhyne said. “The label already has a category C pregnancy caution, which means no adequate, well-controlled studies have been done to determine the effect on the fetus. This is a medicine doctors should already be talking with patients about.”
“Like everything else, it’s a risk-and-benefit ratio,” O’Sullivan said.
SOURCES: Mary Anne Rhyne, spokeswoman, GlaxoSmithKline, Philadelphia; Mary Jo O’Sullivan, M.D., professor, obstetrics and gynecology, University of Miami School of Medicine; Sept. 28, 2005, U.S. Food and Drug Administration statement
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