In 2003, GSK initiated a retrospective analysis of women, dating back to 1995, who had taken antidepressants in the first trimester of their pregnancies and had given birth to children with major congenital malformations. The study found an association between Paxil and congenital malformations in mothers taking Paxil in the first trimester.

Another study conducted by researchers in Denmark and published in Pharmacoepidemology and Drug Safety in 2005 showed a more than 2-fold increase for congenital malformations in women taking Paxil compared to other antidepressants.

In September 2005, GSK sent out a "Dear Doctor" letter informing physicians throughout the United States that the results of its analysis showed a higher rate of "congenital malformations associated with the use of Paxil as compared to other antidepressants" in infants born to women taking antidepressants during the first trimester of pregnancy. The most common malformations for mothers taking Paxil were cardiovascular, particularly ventricular septal defects ("VSD").

The FDA has issued three Public Health Advisories since December 2005 concerning the risk of congenital heart defects and has changed Paxil's pregnancy category from C to D, which indicates that "there is positive evidence of fetal risk."

"The American Medical Association estimates that over 1 percent of pregnant women in the US, or more than 40,000, are taking antidepressants." Armstrong, Wall St. Journal

Sales of antidepressants in the US last year exceeded $12.5 billion. Armstrong, Wall St. Journal

Paxil crosses the placenta, which could have important implications for the developing fetus.

Serotonin (the neurotransmitter that Paxil primarily affects) plays a roll in the fetal development of the heart.

FDA Public Health Advisories Concerning Paxil Birth Defects

According to an FDA Public Health Advisory dated December 8, 2005 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108527.htm

A study using a Swedish national registry found a 2-fold increased risk of having an infant with a cardiac defect compared to the entire national registry population.

In another study in the US, women who received Paxil in the first trimester of their pregnancies had a 1.5-fold increased risk of cardiac malformations.

In March/April 2006

The FDA updated its data on Paxil and the Risk of Birth Defects, explaining that early results of two studies "indicate that women who took Paxil during the first three months of pregnancy were about one and a half 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. 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)." The FDA advised "health care professionals not to prescribe Paxil in women who are in the first three months of pregnancy or are planning pregnancy, unless other treatment options are not appropriate."

On July 19, 2006

The FDA issued another Public Health Advisory titled "Treatment Challenges of Depression in Pregnancy." Ironically, the FDA cites a study that warns of depression relapse in women who decide to stop taking their antidepressant, which study has received a great deal of criticism and was the topic of a front-page Wall Street Journal article exposing the fact that most of the authors of the study had undisclosed financial ties to antidepressant manufacturers. http://www.paxilbirthdefect.com/news.shtml Notwithstanding, the new advisory warns of the recent study by Christina Chambers concerning the risk of pulmonary hypertension in babies born to mothers who took antidepressants in their third trimester of pregnancy.

Paxil Label Regarding Pregnancy

In 2003, the prescribing information for Paxil stated: "Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy."

The label also described GSK's animal studies as having "revealed no evidence of teratogenic effects." ("Teratogen" means any substance with the potential to cause birth defects.) Paxil was identified as a Category C drug (Category C drugs are those in which: "Either animal studies indicate a fetal risk and there are no controlled studies in women, or there are no available studies in women or animals.) The label also stated: "There are no adequate and well-controlled studies in pregnant women." The label further states that Paxil "should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."

The FDA has changed Paxil's pregnancy category from C to D (Category D: "There is positive evidence of fetal risk, but there may be certain situations where the benefit might outweigh the risk [life-threatening or serious diseases where other drugs are ineffective or carry a greater risk].)

Other Complications of Taking Paxil During Pregnancy

A study published in Teratology Society Abstracts in 2005 reported that women who took Paxil were more likely than those who were not exposed to have an infant with omphalocele (a fetal malformation in which variable amounts of abdominal contents protrude into the base of the umbilical cord) and craniosynostosis (the early closing of one or more of the sutures of an infant's head, resulting in malformation of the skull). The strongest effect was reported to be with Paxil.

A recent study published in the New England Journal of Medicine (NEJM) by Christina Chambers of the University of California, San Diego, found a six-fold increased risk of persistent pulmonary hypertension (PPH) in infants born to mothers who took an antidepressant in the last trimester of pregnancy.