Why is bupropion (Wellbutrin) contraindicated in pregnancy and breastfeeding?

Bupropion in Pregnancy and Breastfeeding: Safety Concerns

Bupropion is not strictly contraindicated in pregnancy but should be used with caution during breastfeeding due to two documented cases of seizures in breastfed infants and the presence of the drug in breast milk. 1, 2

Pregnancy Safety Profile

Congenital Malformations

• Bupropion does not appear to be strongly associated with major congenital malformations overall, but there are specific cardiovascular concerns:
  • Possible small increased risk of left ventricular outflow tract obstruction heart defects (0.279% vs 0.07% with other antidepressants) 1
  • Possible increased risk of ventricular septal defects (adjusted OR 2.9; 95% CI 1.5-5.5) 1
  • Potential risk for diaphragmatic hernia, though with a small absolute risk given its rarity (population prevalence 0.012%-0.031%) 1

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion 1, 3
• One case report of poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1

Long-term Outcomes

• Further research needed to clarify possible increased risk for ADHD in children exposed prenatally 1
• Bupropion and its active metabolites cross the placenta to fetal circulation 4
• Hydroxybupropion and threohydrobupropion concentrations in umbilical cord venous plasma are higher than bupropion concentrations, suggesting greater fetal exposure to the metabolites 4

Breastfeeding Safety Concerns

Presence in Breast Milk

• Bupropion is present in human milk and has been detected in the serum of breastfed infants, although typically at very low or sometimes undetectable levels 1, 2, 5
• Average daily infant exposure is approximately 2% of the maternal weight-adjusted dose 5

Documented Adverse Events

• Two case reports of seizures in breastfed infants whose mothers were taking bupropion 1, 2, 6
• Generally, no adverse events reported in most cases of bupropion exposure during breastfeeding 2

Risk Management During Breastfeeding

High-Risk Situations

• Premature or compromised infants may be at higher risk when exposed to bupropion through breast milk 2
• Infants with a history of seizures should not be exposed to bupropion through breast milk 2

Monitoring Recommendations

• Watch for vomiting, diarrhea, jitteriness, sedation, and/or seizures in the infant 2
• Use the lowest effective dose when necessary during breastfeeding 2
• Consider timing breastfeeding to avoid peak maternal drug concentrations 2

Alternative Medications

• For depression during breastfeeding: Consider medications with better established safety profiles during lactation 2
• For ADHD during breastfeeding: Methylphenidate-based medications may be safer alternatives as they have different chemical structures than bupropion 2

Common Pitfalls

• Failing to monitor infants for neurological symptoms when mothers take bupropion while breastfeeding
• Not considering the increased risk in infants with a history of seizures or premature/compromised infants
• Overlooking the potential for drug interactions, as bupropion inhibits CYP2D6 5
• Not recognizing that bupropion lowers seizure threshold, which may be particularly relevant in the context of neonatal exposure 5

While bupropion is not absolutely contraindicated in pregnancy based on current evidence, caution is warranted during breastfeeding due to the documented cases of seizures in breastfed infants, despite their rarity.