Is bupropion (Wellbutrin) safe during pregnancy?

Bupropion (Wellbutrin) Use in Pregnancy

Bupropion can be used during pregnancy when clinically indicated, as it does not appear to substantially increase the risk of major congenital malformations or adverse obstetrical outcomes, though caution is advised regarding specific cardiovascular defects.

Overall Safety Profile

According to the most recent 2024 guidelines, bupropion does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes, although data are limited 1. The FDA drug label confirms that epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall 2.

Specific Cardiovascular Concerns

While the overall safety profile is reassuring, there are two specific cardiovascular malformations that warrant attention:

Left Ventricular Outflow Tract Obstruction (LVOTO)

• Small absolute increase in risk (incidence 0.279% vs 0.07% with other antidepressants) 1
• Confounding by indication cannot be ruled out, and other studies have not consistently found this association 1, 2

Ventricular Septal Defects (VSD)

• Adjusted odds ratio of 2.9 (95% CI: 1.5-5.5) in one study 1
• One case-control study found elevated risk (adjusted OR 2.5; 95% CI: 1.3-5.0) for bupropion alone 3
• However, other large studies did not confirm this association 2, 4

Diaphragmatic Hernia

• Possible increased risk (adjusted OR 2.77; 95% CI: 1.34-5.71) in one study 1
• Small absolute risk given the rarity of this condition (population prevalence 0.012%-0.031%)
• Other studies have not found this association

Other Pregnancy Outcomes

• Possible increased risk for spontaneous abortion, but confounding by indication cannot be ruled out 1
• One case report of poor neonatal adaptation with seizures due to hyperinsulinism 1
• No evidence of increased preterm birth or low birth weight in meta-analysis 5

Clinical Decision-Making Algorithm

When to Consider Bupropion in Pregnancy:

1. Primary indication: Depression requiring pharmacotherapy, especially with concurrent smoking cessation needs 1
2. Switching scenarios: Consider switching from stimulants to bupropion in the perinatal period, particularly for individuals requiring treatment for co-occurring depression 1
3. Risk-benefit assessment: The magnitude of documented risks is very low, and treatment should not be stopped if required for daily functioning 1

Key Considerations:

• Bupropion is less efficacious than stimulants for ADHD but has more pregnancy safety data 1
• The consensus is that it is safer to treat depression with medications than to have uncontrolled symptoms during pregnancy 6
• Untreated depression increases risks of perinatal mortality, pre-eclampsia, preterm birth, and low birth weight 6

Evidence Quality Assessment

The evidence base shows:

• Large epidemiological studies (International Bupropion Pregnancy Registry with 675 first-trimester exposures; UnitedHealthcare database with 1,213 exposures) show no overall increased malformation risk 2, 4
• Inconsistent findings across studies regarding specific cardiac defects suggest these may be chance findings or confounded by maternal smoking/depression 2
• Meta-analysis found congenital malformation rate of 1.0% (95% CI: 0.0%-3.0%), which is within normal population rates 5

Practical Recommendations

If continuing or initiating bupropion during pregnancy:

• Engage in shared decision-making with the patient about the small, inconsistent cardiovascular risks
• Consider fetal echocardiography if first-trimester exposure occurred, though routine screening is not mandated
• Monitor pregnancy carefully, including fetal growth and blood pressure
• Use the lowest effective dose
• Do not abruptly discontinue if medication is needed for functioning

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry (National Pregnancy Registry for Antidepressants: 1-844-405-6185) 2.

Important Caveat

The absolute risks remain small even for the concerning cardiac defects, and the evidence is limited by small numbers of exposed cases, inconsistent findings across studies, and inability to fully control for confounding by indication (maternal depression and smoking both independently affect pregnancy outcomes) 1, 2.