Is bupropion safe for use during pregnancy?

Bupropion Use During Pregnancy

Bupropion can be used during pregnancy with caution, as it does not appear to be associated with major congenital malformations or significant adverse obstetrical outcomes overall, though small increases in specific cardiovascular defects have been reported in some studies but not confirmed in others. 1

Overall Safety Profile

The most recent 2024 American Journal of Obstetrics and Gynecology guidelines state that bupropion does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes, although data are limited. 1

Congenital Malformations - Key Concerns

The evidence shows conflicting findings regarding specific cardiac defects:

• Two cardiovascular malformations have shown small absolute risk increases with first-trimester bupropion monotherapy exposure: 1

  • Left ventricular outflow tract obstruction heart defects (incidence 0.279% vs 0.07% with exposure to other antidepressants)
  • Ventricular septal defects (aOR 2.9; 95% CI 1.5-5.5)

• However, confounding by indication cannot be ruled out, and other studies have not found these associations. 1 A 2007 study found no increased prevalence of cardiovascular malformations (prevalence 10.7 per 1000 with bupropion vs 10.8 per 1000 with other antidepressants, aOR 0.97; 95% CI 0.52-1.80). 2

• Possible increased risk for diaphragmatic hernia (aOR 2.77; 95% CI 1.34-5.71) in one study, but the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%), and other studies have not replicated this finding. 1

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion, though confounding by indication cannot be ruled out. 1

• Possible increased risk for poor neonatal adaptation, but this has been reported in only one case (presenting with seizures due to prolonged hypoglycemia from severe hyperinsulinism). 1

Long-Term Outcomes

Further research is needed to clarify possible increased risk for ADHD in offspring and to disentangle likely confounding by indication. 1

Clinical Context and Indications

For Depression Treatment

Bupropion may be particularly useful for pregnant women requiring treatment for depression, especially when combined with smoking cessation needs, given the available safety data. 1 The 2024 guidelines note that switching from stimulants to bupropion in the perinatal period may be considered for individuals requiring treatment for co-occurring depression, though bupropion is not as efficacious as stimulants for ADHD treatment. 1

For Smoking Cessation

The FDA label classifies bupropion as requiring caution in pregnancy, advising patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy. 3 The label recommends discussing the risk to the unborn baby and mentions a National Pregnancy Registry for Antidepressants (1-844-405-6185). 3

For smoking cessation specifically, the 2021 USPSTF guidelines note that no adequate, well-controlled studies of bupropion use during pregnancy exist in humans, though FDA labeling indicates some fetal harms in animal studies. 4 The 2015 USPSTF guidelines classified bupropion as pregnancy category C. 5

However, a 2020 population-based cohort study found that pregnancy exposure to bupropion was not associated with increased risk of adverse birth outcomes. 6 A 2019 systematic review and meta-analysis found no strong evidence of major positive or negative outcomes associated with gestational bupropion use. 7

Practical Recommendations

When bupropion is clinically necessary during pregnancy:

• Continue the medication if required for daily functioning of the pregnant person, as the magnitude of documented risks is very low. 1

• Engage in shared decision-making with the patient, discussing the limited but generally reassuring safety data versus the risks of untreated depression or continued smoking. 5, 3

• Monitor pregnancy carefully, including fetal growth, blood pressure checks, and ensuring appropriate weight gain. 1

• Consider the lowest effective dose. 1

• Register pregnancy exposures with the National Pregnancy Registry for Antidepressants (1-844-405-6185). 3

Breastfeeding Considerations

Caution is advised during breastfeeding: 1

• Bupropion is present in human milk and has been detected in infant serum at very low levels (sometimes undetectable)
• Generally no adverse events reported in very limited data (21 cases)
• Two case reports of seizures in breastfed infants exist
• The FDA label advises discussing the best way to feed the baby during bupropion treatment 3

Common Pitfalls to Avoid

• Do not automatically discontinue bupropion upon pregnancy confirmation if the medication is essential for maternal functioning - the risks of untreated depression or continued smoking may outweigh the small potential risks. 1

• Do not confuse the cardiovascular malformation signals with definitive causation - confounding by indication (smoking, depression severity) has not been adequately controlled in most studies. 1, 8, 2

• Do not overlook that most evidence comes from smoking cessation use - the indication itself (smoking) carries independent risks for adverse pregnancy outcomes. 6, 9