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 Outcomes

Cardiovascular Malformations

• First-trimester bupropion exposure is associated with an adjusted odds ratio of 2.9 (95% CI, 1.5-5.5) for left ventricular outflow tract obstruction and ventricular septal defects 1
• The absolute risk remains low despite this relative increase 1, 2
• Paroxetine and fluoxetine carry higher risks for cardiac defects than bupropion, making bupropion a reasonable alternative SSRI when antidepressant treatment is required 3

Other Structural Defects

• Possible increased risk for diaphragmatic hernia (aOR 2.77; 95% CI, 1.34-5.71), though the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%) 1
• No evidence of increased major malformations overall 1, 2, 4

Pregnancy Loss

• One study found higher rates of spontaneous abortion compared to non-teratogen controls, though rates remained within the general population baseline 1, 4
• This finding is consistent with other antidepressants and may reflect confounding by indication (the underlying depression or smoking) rather than medication effect 4

Clinical Decision-Making Algorithm

When to Consider Bupropion

• For pregnant women with depression requiring pharmacotherapy, particularly when they are also attempting smoking cessation 2
• As an alternative to SSRIs (paroxetine, fluoxetine) that carry higher cardiac malformation risks 3
• When already taking bupropion pre-conception at an effective, well-tolerated dose, engage in risk-benefit discussion about continuing versus intermittent use 1

Monitoring Requirements During Pregnancy

• Fetal growth surveillance 1
• Blood pressure monitoring 1
• Maternal weight gain assessment 1
• Consider fetal echocardiography if first-trimester exposure occurred, given the small increased cardiovascular risk 1

Neonatal Considerations

Immediate Postnatal Period

• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1
• Monitor newborns for adaptation issues in the immediate postnatal period 1

Long-Term Outcomes

• Possible increased risk for ADHD in offspring requires further research, though confounding by indication (maternal ADHD or depression) is likely 1

Breastfeeding Guidance

Safety Profile

• Bupropion is present in human milk and detectable in infant serum, though typically at very low or undetectable levels 1, 5
• Two case reports of seizures in breastfed infants exist despite generally low drug transfer 1, 5

Management During Lactation

• Maintain the therapeutic dose while breastfeeding rather than reducing to subtherapeutic levels 1, 5
• Monitor infants carefully for seizures, vomiting, diarrhea, jitteriness, and sedation 1, 5
• Ensure appropriate weight gain and developmental milestones 1, 5
• Educate mothers on warning signs requiring immediate medical attention, particularly seizure activity, excessive sedation, and poor feeding 5

Critical Caveats

Confounding by Indication

• Many observed risks cannot definitively be attributed to bupropion versus the underlying condition (depression, smoking) 1, 2
• Untreated maternal depression carries its own risks to pregnancy outcomes and fetal development 6

Comparative Safety

• Bupropion appears safer than paroxetine and fluoxetine for cardiac malformations 3
• SSRIs as a class show evidence for increased risks of preterm birth, neonatal adaptation symptoms, and persistent pulmonary hypertension 3
• Bupropion was not associated with preeclampsia risk, unlike SNRIs and tricyclics 7

FDA Labeling Requirements

• Patients should be advised to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy 8
• A pregnancy exposure registry exists for monitoring outcomes (1-844-405-6185) 8
• Bupropion passes into breast milk, requiring discussion about feeding options 8

Risk-Benefit Framework

The benefits of treating maternal depression or supporting smoking cessation may outweigh the small absolute risks of cardiovascular defects in many clinical scenarios. 1, 2 The decision must weigh:

• Small absolute increase in specific cardiac defects (though relative risk is elevated) 1
• Risks of untreated maternal depression on pregnancy outcomes, maternal health, and infant development 6
• Comparative safety profile favoring bupropion over certain SSRIs for cardiac malformations 3
• Individual patient factors including severity of depression, prior treatment response, and smoking status 1, 2