Bupropion is commonly used to treat depression, and is also prescribed to support smoking cessation. Early data on bupropion-exposure during pregnancy raised concern for a possible increase in risk of malformations of the heart and large blood vessels in bupropion-exposed infants. Subsequent data from bupropion pregnancy registries has been reassuring, however, and do not demonstrate an overall increase in risk of cardiac defects following first trimester bupropion exposure. Although the overall risk of cardiac defects was not increased, the distribution of specific defects in these registries was unexpected in some ways. For example, the GlaxoSmithKline Bupropion Pregnancy Registry included two cases of coarctation of the aorta out of the 675 bupropion-exposed infants, compared to the rate of 6 cases per 10,000 births in the general population.

A recent study was designed to clarify the risks of specific cardiac defects in bupropion-exposed infants (Louik et al, 2014). In this study, researchers interviewed the mothers of 7913 infants with cardiac defects (as well as a comparable group without defects) to learn whether or not the infant had been exposed to bupropion during the first trimester. They then determined odds ratios for bupropion exposure in relation to specific types of malformations, including ventricular septal defects (VSD), coarctation of the aorta, and hypoplastic left heart syndrome (HLHS).

Results are notable for a slightly increased association between bupropion exposure and VSD (OR 1.6, 95% confidence interval 1.0-2.8). Interestingly, this risk was lower for women who were taking another antidepressant along with bupropion, a finding that could not be accounted for by either dose or gestational timing. Risk estimates for other cardiac defects (including coarctation of the aorta and HLHS) in relation to bupropion exposure were not elevated.

It is important to put this reported association between bupropion exposure and VSD in perspective – if we assume this estimate is correct, the absolute risk of VSD following bupropion exposure remains very low. Especially given data that the overall risk of cardiac defects following bupropion exposure are not elevated, for many women bupropion may present the best treatment option for depression or smoking cessation during pregnancy. As with all psychotropic medications, a risk-benefit consideration that includes the risks of untreated psychiatric illness during pregnancy should help guide this decision.

Charlotte Hogan, MD

Louik C, Kerr S, Mitchell A. First-trimester exposure to bupropion and risk of cardiac malformations. Pharmacoepidemiol Drug Saf. 2014 Jun 12.