Is Wellbutrin (Bupropion) Safe in Pregnancy?
Bupropion can be used during pregnancy when clinically necessary, as it does not appear to increase the risk of major congenital malformations above baseline, though there are small absolute increases in specific cardiovascular defects that require informed discussion. 1
Risk Profile for Congenital Malformations
Bupropion does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes overall, though data remain limited. 1, 2
However, two specific cardiovascular malformations show small absolute risk increases with first-trimester exposure:
- Left ventricular outflow tract obstruction 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 diaphragmatic hernia risk (adjusted odds ratio 2.77; 95% CI, 1.34-5.71), though the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%) 1, 2
Critical caveat: Confounding by indication cannot be ruled out in these studies, as the underlying conditions (depression or smoking) may contribute to observed risks rather than the medication itself. 1, 2
Obstetrical Outcomes
- Possible increased risk for spontaneous abortion has been reported, though this rate remains within the general population range and is similar to other antidepressants. 1, 2, 3
- One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism. 1, 2
Long-Term Developmental Outcomes
- Further research is needed to clarify possible increased risk for ADHD in offspring, though confounding by indication is likely. 1, 2
Clinical Decision Algorithm
If already taking bupropion before pregnancy:
- Engage in a risk-benefit discussion regarding continuing at the current well-tolerated, effective dose versus considering intermittent use. 2
- The benefits of treating maternal depression or supporting smoking cessation may outweigh potential risks in many cases, particularly given the absolute risk of cardiovascular defects remains relatively low even if increased. 2
Monitoring during pregnancy:
- Monitor fetal growth carefully 2
- Check blood pressure regularly 2
- Ensure appropriate maternal weight gain 2
Pharmacokinetic considerations:
- No dose adjustment is necessary during pregnancy, as pregnancy does not significantly alter bupropion metabolism or metabolite concentrations. 4
- The placenta provides a partial barrier, with umbilical cord concentrations 30%-60% lower than maternal plasma concentrations. 4
Breastfeeding Considerations
Caution is advised during breastfeeding based on very limited data (21 cases). 1, 2, 5
- Bupropion is present in human milk and has been detected in infant serum, though typically at very low or sometimes undetectable levels. 1, 2, 5, 6
- Two case reports of seizures in breastfed infants exist, despite generally low drug transfer. 1, 2, 5
If bupropion is clinically necessary during breastfeeding:
- Maintain the therapeutic dose while breastfeeding 2, 5
- Monitor the infant carefully for seizures, vomiting, diarrhea, jitteriness, and sedation 2, 5
- Ensure appropriate infant weight gain and developmental milestones 2, 5
- Educate the mother on warning signs requiring immediate medical attention, particularly seizure activity, excessive sedation, and poor feeding 5
Important Contraindications from FDA Labeling
Do not use bupropion if the patient has: 6