Is Wellbutrin (bupropion) safe to take during pregnancy?

Bupropion Use During Pregnancy

Bupropion can be used during pregnancy when the benefits of treating maternal depression or supporting smoking cessation outweigh the small absolute risk of specific cardiovascular malformations, particularly ventricular septal defects. 1

Safety Profile and Malformation Risk

Bupropion does not appear to cause major congenital malformations overall, though specific cardiovascular defects warrant attention 1, 2:

• A small absolute increase in risk exists for two specific cardiovascular malformations with first-trimester exposure: left ventricular outflow tract obstruction and ventricular septal defects (VSD), with an adjusted odds ratio of 2.9 (95% CI, 1.5-5.5) 1
• The VSD risk is particularly elevated when bupropion is used alone (aOR 2.5,95% CI 1.3-5.0) rather than in combination with other antidepressants 3
• Despite this increased relative risk, the absolute risk remains low given the baseline prevalence of these defects 1, 2
• 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

Other Pregnancy Outcomes

Additional obstetrical considerations include 1, 4:

• A possible increased risk for spontaneous abortion has been reported, though rates remain within the general population range 1, 4
• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1
• No consistent evidence suggests increased rates of stillbirth, preterm birth, or low birth weight when compared to other antidepressants 4, 5

Clinical Decision-Making Algorithm

For women already taking bupropion before pregnancy:

• Engage in a risk-benefit discussion regarding continuing at the current effective dose versus considering intermittent use 1
• Weigh the small absolute cardiovascular risk against the substantial risks of untreated depression or continued smoking 2
• Consider that confounding by indication (depression itself or smoking) may contribute to observed risks 1, 2

For women considering starting bupropion during pregnancy:

• Bupropion may be a reasonable option, particularly when treating both depression and supporting smoking cessation simultaneously 2
• The cardiovascular malformation risk should be discussed, emphasizing the small absolute increase 1
• Alternative antidepressants (particularly SSRIs) do not show the same cardiovascular signal and may be preferred if smoking cessation is not a concurrent goal 5, 6

Monitoring During Pregnancy

Women taking bupropion during pregnancy require 1:

• Careful monitoring of fetal growth throughout pregnancy 1
• Blood pressure checks to detect hypertension or preeclampsia 1
• Assessment of appropriate maternal weight gain 1
• Consideration of fetal echocardiography if first-trimester exposure occurred, given the VSD risk 3

Breastfeeding Considerations

Bupropion can be used cautiously during breastfeeding with careful infant monitoring:

• Bupropion is present in human milk but typically at very low or undetectable levels in infant serum 1, 7
• Two case reports document seizures in breastfed infants, making this a serious though rare concern 1, 7
• The therapeutic dose should be maintained while breastfeeding rather than reduced, as subtherapeutic dosing provides no benefit 7
• Monitor the infant carefully for seizures, vomiting, diarrhea, jitteriness, sedation, and appropriate weight gain and developmental milestones 1, 7
• Mothers should be educated on warning signs requiring immediate medical attention, particularly seizure activity, excessive sedation, and poor feeding 7

Critical Caveats

The most important pitfall to avoid is dismissing the benefits of treating maternal depression or supporting smoking cessation 2:

• Untreated maternal depression carries substantial risks for both mother and fetus that may exceed the small absolute cardiovascular risk 2
• Continued smoking during pregnancy has well-established adverse effects that likely outweigh bupropion's risks 2
• The elevated cardiovascular risk may be partially explained by confounding by indication, as the underlying conditions (depression, smoking) themselves carry risks 1, 2