Is bupropion (Wellbutrin) safe to use during pregnancy for anxiety and depression?

Bupropion Safety During Pregnancy for Anxiety and Depression

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

Potential Risks During Pregnancy

Congenital Malformations

• Bupropion does not seem to be associated with major congenital malformations overall, although data are limited 1
• There is a possible small absolute increase in risk for specific cardiovascular malformations with first-trimester exposure:
  • 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, 2
• Possible increased risk for diaphragmatic hernia, though this has a small absolute risk given the rarity of the condition (population prevalence 0.012%-0.031%) 1
• Confounding by indication cannot be ruled out in these associations 1

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion 1, 3
• 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 needed to clarify possible increased risk for ADHD in offspring 1
• Bupropion and its active metabolites cross the placenta to fetal circulation 4
• Concentrations of hydroxybupropion and threohydrobupropion in umbilical cord venous plasma were higher than bupropion concentrations, suggesting higher fetal exposure to the metabolites 4

Breastfeeding Considerations

• Bupropion is present in human milk and has been detected in the serum of infants exposed through breastfeeding, although typically at very low or sometimes undetectable levels 1, 5
• Generally, no adverse events reported in most cases 1, 5
• However, there have been two case reports of seizures in breastfed infants whose mothers were taking bupropion 1, 5
• Caution is advised during breastfeeding 5

Clinical Decision-Making Algorithm

1. Assess severity of maternal anxiety and depression

   • If symptoms are mild to moderate, consider non-pharmacological interventions first
   • If symptoms are severe or non-pharmacological interventions ineffective, proceed to medication consideration

2. Consider timing in pregnancy

   • First trimester: Highest concern for cardiovascular malformations
   • Third trimester: Discontinuing bupropion before delivery may reduce risk of NICU admission 6

3. Evaluate individual risk factors

   • History of smoking (bupropion is used for smoking cessation)
   • Previous response to bupropion or other antidepressants
   • Presence of other medical conditions

4. Monitoring recommendations if bupropion is continued

   • Consider detailed fetal cardiac ultrasound if exposed during first trimester
   • Monitor for signs of spontaneous abortion
   • Use lowest effective dose 5
   • Consider discontinuing before delivery to reduce risk of neonatal adaptation syndrome 6

Important Caveats

• The FDA pregnancy registry encourages healthcare providers to register patients taking antidepressants during pregnancy 7
• Untreated depression during pregnancy carries its own risks to both mother and fetus 7
• Women who discontinue antidepressants during pregnancy are more likely to experience relapse of major depression 7
• For breastfeeding mothers requiring treatment for depression or anxiety, medications with better established safety profiles during lactation may be preferable 5
• Infants with a history of seizures should not be exposed to bupropion through breast milk 5

In conclusion, while bupropion does not appear to significantly increase overall risk of major malformations, the potential small increased risk of specific cardiovascular defects and spontaneous abortion warrants careful consideration of the risk-benefit ratio for each patient, with particular attention to the severity of maternal depression and anxiety symptoms.