Is bupropion (Wellbutrin) safe for pregnant women?

Is Bupropion Safe for Pregnant Women?

Bupropion can be used during pregnancy when clinically necessary, as it does not appear to increase the overall risk of major congenital malformations, though small increases in specific cardiovascular defects have been reported and confounding by indication cannot be ruled out. 1, 2

Overall Safety Profile

Bupropion does not seem to be associated with major congenital malformations overall or other significant adverse obstetrical outcomes, though the available data are limited. 1, 3 The FDA label confirms that epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall. 2

• The international bupropion Pregnancy Registry (675 first-trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first-trimester exposures) did not show an increased risk for malformations overall. 2
• A prospective comparative study of 136 women exposed to bupropion during the first trimester found no major malformations among 105 live births. 4

Specific Cardiovascular Concerns

Two specific cardiovascular malformations have shown small absolute risk increases with first-trimester bupropion exposure, but confounding by indication (depression or smoking) cannot be excluded:

• Left ventricular outflow tract obstruction (LVOTO) heart defects: The incidence increased from 0.07% with other antidepressants to 0.279% with bupropion exposure. 1 However, study findings are inconsistent and do not allow definitive conclusions. 2
• Ventricular septal defects: Adjusted odds ratio of 2.9 (95% CI, 1.5-5.5). 1, 3
• Diaphragmatic hernia: Possible increased risk (aOR 2.77; 95% CI, 1.34-5.71), though the absolute risk remains extremely small given the rarity of this condition (population prevalence 0.012%-0.031%). 1, 3

The prospectively observed rate of cardiovascular malformations from the international Pregnancy Registry was 1.3%, which is similar to the background rate of approximately 1%. 2

Other Obstetrical Outcomes

• Spontaneous abortion: Possible increased risk, though this finding is similar to other studies examining antidepressants during pregnancy and confounding by indication cannot be ruled out. 1, 3, 4 One prospective study found significantly more spontaneous abortions in the bupropion group (P = .009), but rates remained within the general population range. 4
• Poor neonatal adaptation: One case report noted seizures due to prolonged hypoglycemia from severe hyperinsulinism, but this represents an isolated finding. 1, 3

Clinical Decision-Making Algorithm

When bupropion is already being taken before pregnancy:

1. Engage in a risk-benefit discussion regarding continuing at the current well-tolerated, effective dose versus considering intermittent use. 1, 3
2. Consider the substantial risks of untreated maternal depression, including premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship. 2
3. Women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than those who continued treatment. 2

During pregnancy monitoring:

• Monitor pregnancy carefully, including fetal growth assessments. 1, 3
• Ensure blood pressure checks throughout pregnancy. 1, 3
• Verify appropriate maternal weight gain. 1, 3

Alternative consideration for ADHD patients:

Bupropion can be considered as an alternative to stimulants in the perinatal period, particularly for individuals requiring treatment for co-occurring depression, given the available safety data, though it is not as efficacious as stimulants for ADHD treatment. 1, 3

Smoking Cessation Context

The U.S. Preventive Services Task Force found inadequate evidence on the benefits of bupropion for tobacco cessation in pregnant women and no evidence on harms. 1 Two randomized controlled trials showed that bupropion was not efficacious in promoting smoking cessation during pregnancy, despite being well-tolerated. 5, 6 One trial found no significant difference in 7-day point prevalence abstinence rates at the end of pregnancy (10% vs 3%, P = .328). 5

Important Caveats

• Confounding by indication is a critical limitation across most studies, as the underlying conditions (depression or smoking) may independently contribute to observed risks. 1, 3, 2
• The absolute risk of cardiovascular defects, even if increased, remains relatively low. 3
• Benefits of treating maternal depression may outweigh potential risks in many clinical scenarios, as untreated depression carries substantial documented risks to both mother and infant. 2
• Healthcare providers are encouraged to register patients in the National Pregnancy Registry for Antidepressants (1-844-405-6185). 2