Is Wellbutrin (bupropion) safe during pregnancy?

Safety of Wellbutrin (Bupropion) During Pregnancy

Bupropion should be used with caution during pregnancy due to potential small increased risks of cardiovascular malformations and spontaneous abortion, though it does not appear to be associated with major congenital malformations overall. 1

Risk Assessment

Congenital Malformations

• Bupropion has been associated with a small absolute increase in risk for specific cardiovascular malformations:
  • Left ventricular outflow tract obstruction heart defects (incidence 0.279% vs 0.07% with other antidepressants) 1
  • Ventricular septal defects (adjusted odds ratio 2.9; 95% CI, 1.5-5.5) 1
  • Possible increased risk for diaphragmatic hernia, though this has a small absolute risk given the rarity of this condition (population prevalence 0.012%-0.031%) 1

However, it's important to note that confounding by indication cannot be ruled out, and other studies have not found these associations.

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion 1, 2
• One case report noted poor neonatal adaptation with seizures due to prolonged hypoglycemia as a consequence of severe hyperinsulinism 1

Long-term Outcomes

• Further research is needed to clarify possible increased risk for ADHD in offspring 1
• Likely confounding by indication in studies showing associations with developmental outcomes

Placental Transfer

• Bupropion and its active metabolites cross the placenta to the fetal circulation 3
• Umbilical cord venous plasma to maternal plasma ratios:
  • Bupropion: median 0.53
  • Hydroxybupropion: median 0.21
  • Threohydrobupropion: median 0.61 3
• Concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations, suggesting higher fetal exposure to the metabolites 3

Breastfeeding Considerations

• Bupropion is present in human milk and has been detected in the serum of infants exposed via breastfeeding, though at very low levels (sometimes undetectable) 1
• Generally, no adverse events reported in breastfed infants, but there have been two case reports of seizures 1

FDA Guidance

The FDA label for bupropion indicates:

• Women who are pregnant should discuss the risks with their healthcare provider 4
• Women who become pregnant during treatment should consider registering with the National Pregnancy Registry for Antidepressants 4

Clinical Decision Algorithm

1. Assess necessity of treatment:

   • Evaluate severity of depression or need for smoking cessation
   • Consider risks of untreated depression during pregnancy (poor prenatal care, substance use, postpartum depression)

2. Consider alternatives:

   • For depression: SSRIs with better pregnancy safety data might be preferred first-line options
   • For smoking cessation: behavioral interventions may be tried first

3. If bupropion is determined to be necessary:

   • Use the lowest effective dose
   • Consider timing of exposure (first trimester carries highest risk for congenital malformations)
   • Monitor fetal development with appropriate ultrasounds
   • Be vigilant for signs of spontaneous abortion

4. Postpartum considerations:

   • Monitor infant for potential adverse effects if breastfeeding
   • Be aware of the rare possibility of seizures in breastfed infants

Important Caveats

• The absolute risk of cardiovascular malformations remains low
• Data limitations exist in most studies on bupropion in pregnancy
• Benefits of treating depression during pregnancy may outweigh potential risks
• Pharmacokinetic studies suggest pregnancy does not significantly alter bupropion metabolism, so dose adjustments may not be necessary 5