What are the risks of bupropion (Wellbutrin) during pregnancy?

From the Guidelines

Bupropion use during pregnancy is not recommended due to limited evidence on its safety and potential risks to the fetus. The US Preventive Services Task Force found no studies on bupropion SR for tobacco smoking cessation during pregnancy, highlighting the lack of data on its use in this population 1. While some studies suggest a possible link between bupropion and heart defects or spontaneous abortion, the current evidence is limited and inconclusive. Key considerations for pregnant women include:

• The potential risks of bupropion to the fetus, including heart defects and spontaneous abortion
• The lack of evidence on the safety and efficacy of bupropion for smoking cessation during pregnancy
• The importance of weighing the risks and benefits of bupropion use during pregnancy, particularly for women with a history of depression or smoking
• The need for consultation with both an obstetrician and a psychiatrist to make informed decisions about medication use during pregnancy. Given the limited evidence and potential risks, alternative treatments such as behavioral counseling or other medications should be considered first-line options for pregnant women 1.

From the FDA Drug Label

Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1. 3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%) Study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding possible association.

The risks of bupropion during pregnancy include:

• Congenital malformations: Data from epidemiological studies have not identified an increased risk of congenital malformations overall.
• Cardiovascular malformations: The observed rate of cardiovascular malformations is similar to the background rate.
• Left ventricular outflow tract obstruction (LVOTO): Study findings are inconsistent and do not allow conclusions regarding possible association. It is essential to consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum 2.

From the Research

Risks of Bupropion During Pregnancy

• The use of bupropion during pregnancy has been associated with a small elevation in the risk of cardiovascular defects, although the absolute risk is low 3.
• The risk of miscarriage following prenatal bupropion exposure was higher than that of a control group of women in one study, but remained within the general population rate 3.
• Bupropion and its active metabolites cross the placenta to the fetal circulation, with higher concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma than bupropion concentrations 4.
• A registry of pregnancies exposed to bupropion has shown a higher-than-expected frequency of neonatal cardiac malformations, with 7 of the 10 newborns with malformations having cardiac anomalies 5.
• There is no clear increased risk of major congenital malformations associated with prenatal use of bupropion compared with smoking during the first trimester 6.

Specific Risks

• Cardiovascular defects: bupropion use in the first trimester has been linked with a small elevation in the risk of cardiovascular defects 3.
• Miscarriage: the risk of miscarriage following prenatal bupropion exposure was higher than that of a control group of women in one study, but remained within the general population rate 3.
• Neonatal cardiac malformations: a registry of pregnancies exposed to bupropion has shown a higher-than-expected frequency of neonatal cardiac malformations 5.

Studies and Findings

• A systematic review of 8 studies found that bupropion may be a reasonable treatment option for depressed pregnant women who require pharmacotherapy, particularly when they also are attempting to reduce nicotine use during pregnancy 3.
• A study of 22 women taking bupropion found that bupropion and its active metabolites cross the placenta to the fetal circulation, with higher concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma than bupropion concentrations 4.
• A cohort study of 391,474 infants found no clear increased risk of major congenital malformations associated with prenatal use of bupropion compared with smoking during the first trimester 6.