to the editor: In the FPIN's Clinical Inquiries on which antidepressants are safe to use during pregnancy, Dr. Patel and colleagues suggest that paroxetine (Paxil) is safe. Although they note that the American College of Obstetricians and Gynecologists recommends avoiding paroxetine use during pregnancy, they do not provide the evidence supporting the recommendation. Paroxetine actually carries a category D rating from the U.S. Food and Drug Administration (FDA) for safety in pregnancy.

Two studies have found an association between first trimester paroxetine use and congenital malformations, notably cardiac malformations. The first study, completed in 2005, showed “a trend towards a 1.5-fold increased risk for cardiovascular malformations for paroxetine compared to other antidepressants. This study also showed a statistically significant increased overall risk of major congenital malformations (inclusive of the cardiovascular defects) in infants exposed to paroxetine compared to other antidepressants.”¹

In the second study, an analysis of data from the Swedish Medical Birth Register revealed an association between use of paroxetine and cardiovascular congenital defects, most notably ventricular and atrial septal defects.² On the basis of these two studies and at the FDA's request, GlaxoSmithKline downgraded their rating of paroxetine safety in pregnancy to category D.³

When this information is added to the data presented by the authors, I believe the evidence supports avoiding paroxetine use during pregnancy, especially in the first trimester. Physicians should also consider this evidence when counseling women of childbearing age about medication choices for depression.

in reply: As Dr. Budenholzer points out, paroxetine received a D rating from the FDA. However, in a 2008 study, paroxetine use in early pregnancy did not appear to be associated with an increased risk of cardiovascular defects in infants; the incidence in more than 3,000 infants was within the population incidence of cardiovascular disease of approximately 1 percent.¹

Other studies have found an association between maternal paroxetine use and cardiac malformations in infants. A 2005 study reported a 1.5-fold increased risk of cardiovascular malformations with paroxetine use, although the author counted all diagnosed cardiovascular defects, even those that resolved spontaneously.² In contrast, the teratology information services groups that produced data for the American Journal of Psychiatry study did not include cardiovascular defects that resolved spontaneously.¹ The GlaxoSmithKline results did not specify the severity of the cardiovascular defects, so a number of these cases may have resolved spontaneously.³

I agree with Dr. Budenholzer that paroxetine use during pregnancy should be avoided because of the increased risk of cardiovascular defects in infants, regardless of whether they are categorized as minor, moderate, or severe.