Is Wellbutrin (bupropion) safe to use during pregnancy?

Bupropion Use During Pregnancy

Bupropion can be used during pregnancy when clinically necessary, as it does not appear to increase the risk of major congenital malformations overall, though there is a small absolute increased risk for specific cardiovascular defects (left ventricular outflow tract obstruction and ventricular septal defects) with first-trimester exposure. 1

Risk Profile for Fetal Malformations

• Bupropion is not associated with major congenital malformations overall, though data remain limited 1
• A small but statistically significant increased risk exists for two specific cardiovascular malformations with first-trimester exposure: left ventricular outflow tract obstruction and ventricular septal defects (adjusted odds ratio 2.9; 95% CI, 1.5-5.5) 1
• The absolute risk of these cardiovascular defects remains relatively low even with the increased odds ratio 1
• A possible increased risk for diaphragmatic hernia exists (aOR 2.77; 95% CI, 1.34-5.71), though the absolute risk is extremely small given this condition's rarity (population prevalence 0.012%-0.031%) 1
• Prospective comparative data from 136 first-trimester exposures showed no major malformations, supporting the overall safety profile 2

Obstetrical and Neonatal Outcomes

• A possible increased risk for spontaneous abortion has been reported 1, with one study showing significantly more spontaneous abortions in the bupropion group (P = .009) compared to controls, though rates remained within the general population baseline 2
• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1
• Mean birth weight (3450g) and gestational age at delivery (40 weeks) were not significantly different from controls in prospective studies 2

Clinical Decision-Making Algorithm

For women already taking bupropion before pregnancy:

• Engage in a risk-benefit discussion about continuing at the current effective dose versus considering intermittent use 1
• The benefits of treating maternal depression or supporting smoking cessation may outweigh the small absolute cardiovascular risks in most cases 1
• Do not automatically discontinue if the medication is well-tolerated and effective 1

For women considering starting bupropion during pregnancy:

• Bupropion may be a reasonable treatment option for depressed pregnant women requiring pharmacotherapy, particularly when they are also attempting smoking cessation 3
• Consider that confounding by indication (the underlying depression or smoking itself) may contribute to observed risks 1

Monitoring Requirements During Pregnancy

• Monitor fetal growth carefully throughout pregnancy 1
• Check blood pressure regularly 1
• Ensure appropriate maternal weight gain 1
• Consider fetal echocardiography if first-trimester exposure occurred, given the specific cardiovascular defect risk 1

Critical Caveats

• Confounding by indication cannot be ruled out in many studies, as the underlying condition (depression or smoking) may independently contribute to observed risks 1
• The data remain limited overall, though existing evidence is reassuring for major malformations 1
• Bupropion should be considered as a second-line treatment after psychotherapy when possible, consistent with general antidepressant prescribing principles during pregnancy 4