Is Wellbutrin (bupropion) safe to use during pregnancy?

Wellbutrin (Bupropion) Use During Pregnancy

Bupropion does not appear to increase the risk of major congenital malformations above baseline and can be continued during pregnancy when the benefits of treating maternal depression or supporting smoking cessation outweigh the small absolute increased risk of specific cardiovascular defects. 1

Safety Profile and Malformation Risk

• Bupropion is not associated with an overall increase in major congenital malformations compared to other antidepressants or unexposed controls 1, 2, 3

• However, first-trimester exposure is associated with a small absolute increased risk of two specific cardiac defects: 1

  • Left ventricular outflow tract obstruction heart defects (adjusted odds ratio 2.9; 95% CI, 1.5-5.5) 1
  • Ventricular septal defects (adjusted odds ratio 2.9; 95% CI, 1.5-5.5) 1
  • Despite the elevated odds ratio, the absolute risk remains low given the baseline rarity of these conditions 1, 4

• A possible increased risk for diaphragmatic hernia exists (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, 4

Obstetrical Outcomes

• A possible increased risk for spontaneous abortion has been reported, though rates remain within the general population range and are similar to other antidepressants 1, 2

• Bupropion use during pregnancy is associated with lower risk of prematurity (adjusted odds ratio 0.12; 95% CI, 0.03-0.50) compared to continued smoking 5

• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1

Clinical Decision-Making Algorithm

For women already taking bupropion before pregnancy: 1, 4

1. Engage in risk-benefit discussion regarding continuing at the current effective dose versus considering alternatives 1, 4

2. Consider continuation if:

   • Depression is moderate to severe and previously well-controlled on bupropion 1
   • Patient has failed other antidepressants 1
   • Smoking cessation is a concurrent goal 5
   • The benefits of treating maternal depression outweigh the small absolute increased risk of specific cardiac defects 1, 4

3. Monitor pregnancy carefully with attention to: 1

   • Fetal growth surveillance 1
   • Maternal blood pressure checks 1
   • Appropriate maternal weight gain 1

For women considering starting bupropion during pregnancy: 6

• The FDA label advises patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy 6
• Patients should be informed about the National Pregnancy Registry for Antidepressants (1-844-405-6185) 6
• The decision should weigh untreated maternal depression risks against the small absolute increased risk of specific cardiac defects 1, 4

Important Caveats and Pitfalls

• Confounding by indication cannot be ruled out in many studies, as the underlying condition (depression or smoking) may contribute to observed risks rather than the medication itself 1, 7

• The absolute risk of cardiovascular defects, even if increased, remains relatively low in the context of the baseline population prevalence 1, 4

• All medications for weight management, including combination products containing bupropion, are contraindicated in individuals who are or may become pregnant 4

• Untreated maternal depression carries its own risks to both mother and fetus, which must be weighed against medication risks 1

Breastfeeding Considerations

• Bupropion is present in human milk and has been detected in the serum of breastfed infants, though typically at very low or sometimes undetectable levels 1, 6

• Two case reports document seizures in breastfed infants whose mothers were taking bupropion, despite generally low transfer into breast milk 1

• If bupropion is needed during breastfeeding, maintain the therapeutic dose while carefully monitoring the infant for: 1

  • Vomiting 1
  • Diarrhea 1
  • Jitteriness 1
  • Sedation 1
  • Seizures 1
  • Appropriate weight gain and developmental milestones 1