Is Wellbutrin (bupropion) safe to use during pregnancy?

Wellbutrin (Bupropion) Use During Pregnancy

Bupropion can be used during pregnancy when clinically necessary for treating maternal depression or supporting smoking cessation, as it does not appear to increase the overall risk of major congenital malformations, though careful monitoring is required for specific cardiovascular defects. 1

Safety Profile and Malformation Risk

The overall risk of major congenital malformations with bupropion is not elevated above baseline, which makes it a reasonable treatment option when antidepressant therapy is required during pregnancy. 1, 2, 3

However, there are two specific cardiovascular concerns to be aware of:

• Left ventricular outflow tract obstruction and ventricular septal defects show a small absolute increase in risk with first-trimester exposure (adjusted odds ratio 2.9; 95% CI, 1.5-5.5). 1
• Diaphragmatic hernia may have a possible increased risk (aOR 2.77; 95% CI, 1.34-5.71), though the absolute risk remains extremely low given this condition's rarity (population prevalence 0.012%-0.031%). 1

The absolute risk of these cardiovascular defects remains relatively low even if the relative risk is increased. 1

Obstetrical Outcomes

• Spontaneous abortion rates may be higher with bupropion exposure compared to unexposed controls, though rates remain within the general population range. 1, 2, 3 One prospective study found significantly more spontaneous abortions in the bupropion group (P = .009), a pattern similar to other antidepressants. 3
• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism. 1
• Long-term neurodevelopmental outcomes, including possible ADHD risk in offspring, require further research, though confounding by indication (the underlying maternal condition) likely explains much of any observed association. 1

Clinical Decision-Making Algorithm

Step 1: Assess Clinical Necessity

Weigh the maternal benefit of treating depression or supporting smoking cessation against the potential fetal risks. Untreated maternal depression carries its own significant risks to both mother and fetus, including poor prenatal care, inadequate nutrition, and increased stress hormones affecting fetal development. 4

Step 2: Pre-Pregnancy Counseling

If a woman is already taking bupropion before pregnancy and it is well-tolerated and effective, engage in a thorough risk-benefit discussion about:

• Continuing at the current dose 1
• Considering intermittent use 1
• Switching to alternative treatments

Step 3: Monitoring During Pregnancy

If bupropion is continued or initiated:

• Monitor fetal growth carefully 1
• Check maternal blood pressure regularly 1
• Ensure appropriate maternal weight gain 1
• Consider fetal echocardiography if first-trimester exposure occurred, given the small increased risk of specific cardiac defects 1

Step 4: Comparative Context

Bupropion may be preferable to some other antidepressants during pregnancy. Unlike SNRIs and tricyclics, bupropion has not been associated with increased preeclampsia risk. 5 SSRIs as a class show evidence for major congenital malformations, with paroxetine and fluoxetine specifically linked to congenital heart defects, while sertraline shows no such evidence. 6

Breastfeeding Considerations

Caution is advised during breastfeeding, though bupropion can be used if clinically necessary. 1, 7

• Bupropion is present in human milk and detectable in infant serum, though typically at very low or undetectable levels. 1, 7
• Two case reports document seizures in breastfed infants whose mothers were taking bupropion, despite generally low drug transfer. 1, 7
• If breastfeeding while on bupropion, maintain the therapeutic dose (do not reduce it, as this may compromise maternal treatment) and monitor the infant carefully for seizures, vomiting, diarrhea, jitteriness, sedation, and poor weight gain. 1, 7

Critical Caveats

Confounding by indication is a major limitation in interpreting pregnancy safety data—the underlying depression or smoking behavior may contribute to observed risks rather than the medication itself. 1, 2 This makes it difficult to isolate the true medication effect from the disease effect.

The benefits of treating maternal depression or supporting smoking cessation often outweigh the potential risks in clinical practice, particularly given that the absolute risks remain low. 1, 2