Bupropion Use During Pregnancy
Bupropion can be used during pregnancy when clinically indicated, as it does not appear to increase the overall risk of major congenital malformations above baseline, though there is a small absolute increased risk of specific cardiovascular defects with first-trimester exposure that must be discussed with the patient. 1
Overall Safety Profile
- Bupropion does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes overall, although the available data are limited 1
- The drug and its active metabolites (hydroxybupropion and threohydrobupropion) cross the placenta to the fetal circulation, with fetal exposure occurring primarily to the metabolites rather than the parent drug 2
Specific Cardiovascular Risks to Discuss
First-trimester exposure carries a small absolute increased risk of two specific cardiac malformations:
- Left ventricular outflow tract obstruction heart defects (incidence 0.279% vs 0.07% with exposure to other antidepressants) 1
- Ventricular septal defects (adjusted odds ratio 2.9; 95% CI, 1.5-5.5) 1, 3
Important context: Confounding by indication cannot be ruled out, and other studies have not consistently found these associations 1, 3
Other Potential Risks
- Possible increased risk for diaphragmatic hernia (adjusted odds ratio 2.77; 95% CI, 1.34-5.71), though the absolute risk is extremely small given the population prevalence of only 0.012%-0.031% 1, 3
- Possible increased risk for spontaneous abortion, similar to other antidepressants, though confounding by indication cannot be ruled out 1, 3, 4
- Possible increased risk for poor neonatal adaptation, reported in only one case presenting with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1
Clinical Decision-Making Algorithm
For women already taking bupropion before pregnancy:
- Continue at the current effective dose if the medication is controlling depression or supporting smoking cessation 3
- The benefits of treating maternal depression or supporting smoking cessation may outweigh the small absolute increased risks of specific cardiac defects in most clinical scenarios 3
For women considering starting bupropion during pregnancy:
- Weigh the maternal mental health benefits against the small absolute cardiovascular risks 3
- Consider that untreated depression and continued smoking both carry significant risks to pregnancy outcomes 5, 6
Monitoring during pregnancy:
- Monitor fetal growth, maternal blood pressure, and appropriate weight gain 3
- Consider fetal echocardiography if first-trimester exposure occurred, given the specific cardiac defect associations 1, 3
Important Contraindication
All medications for weight management, including combination products containing bupropion, are contraindicated in individuals who are or may become pregnant 3
Evidence Quality Considerations
The 2024 American Journal of Obstetrics and Gynecology guidelines provide the most recent comprehensive assessment, noting that while data are limited, the overall safety profile is reassuring 1. Prospective studies have shown no major malformations in exposed pregnancies, though sample sizes remain relatively small 4. The elevated odds ratios for specific cardiac defects must be interpreted in the context of their rarity and the possibility of confounding by the underlying maternal condition 1, 3.