Can a pregnant patient with moderate to severe depression be treated with Wellbutrin (bupropion), and what are the safety considerations, recommended dosing, and monitoring?

Bupropion Use in Pregnancy for Depression

Bupropion can be used to treat moderate to severe depression in pregnancy, as it does not appear to increase the risk of major congenital malformations above baseline, though there is a small absolute increased risk of specific cardiovascular defects (left ventricular outflow tract obstruction and ventricular septal defects) with first-trimester exposure. 1

Safety Profile and Risk Assessment

Congenital Malformations

• Overall major malformations are not increased above baseline risk with bupropion exposure during pregnancy 1, 2, 3
• First-trimester exposure carries a small absolute increased risk for two specific cardiac defects: left ventricular outflow tract obstruction and ventricular septal defects (adjusted OR 2.9; 95% CI, 1.5-5.5) 1
• Despite the elevated odds ratio, the absolute risk remains low given the baseline rarity of these conditions 1, 4
• A possible increased risk for diaphragmatic hernia exists (aOR 2.77; 95% CI, 1.34-5.71), though the absolute risk is extremely small given the population prevalence of only 0.012%-0.031% 1, 4

Other Pregnancy Outcomes

• Possible increased risk for spontaneous abortion has been reported, though rates remain within the general population range 1, 3
• One case report documented poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism 1
• No evidence of increased preterm birth or low birthweight when used for depression (mean birthweight 3450g, mean gestational age 40 weeks) 3

Placental Transfer

• Bupropion and its active metabolites (hydroxybupropion and threohydrobupropion) cross the placenta, with fetal exposure higher to metabolites than the parent drug 5
• Median umbilical cord to maternal plasma ratios: bupropion 0.53, hydroxybupropion 0.21, threohydrobupropion 0.61 5

Clinical Decision Algorithm

When to Continue Bupropion

• If already taking bupropion before pregnancy and it is well-tolerated and effective, continue at the current therapeutic dose rather than switching or discontinuing 1
• The benefits of treating maternal depression outweigh the small absolute increased risks of specific cardiac defects in most clinical scenarios 1, 4
• Untreated depression carries significant risks including spontaneous abortion, preterm birth, and negative impacts on fetal development 6

When to Consider Alternatives

• If the patient is not yet pregnant and planning conception, discuss the small increased risk of specific cardiovascular defects and consider whether an alternative antidepressant with a more established safety profile (such as certain SSRIs) might be appropriate 7
• Bupropion should NOT be used for weight management in pregnancy—all weight management medications containing bupropion are contraindicated 4

Dosing Recommendations

• Maintain the therapeutic dose that was effective pre-pregnancy—do not reduce dosing arbitrarily 1
• Standard dosing for depression: Start 150 mg once daily, may increase to 300 mg daily (extended-release formulation) 2
• Use low initial doses and increase gradually in patients at higher seizure risk 2

Monitoring During Pregnancy

Maternal Monitoring

• Regular blood pressure checks throughout pregnancy 1
• Ensure appropriate maternal weight gain according to gestational guidelines 1
• Monitor for signs of worsening depression or suicidal ideation 2

Fetal Monitoring

• Perform regular fetal growth assessments throughout pregnancy 1
• Consider fetal echocardiography at 18-22 weeks if first-trimester exposure occurred, given the small increased risk of specific cardiac defects 1, 4

Neonatal Monitoring

• Monitor newborn for signs of poor neonatal adaptation, particularly hypoglycemia and seizures 1
• Assess for any withdrawal symptoms or jitteriness in the immediate postpartum period 1

Breastfeeding Considerations

• Bupropion can be continued during breastfeeding at the therapeutic dose, with careful infant monitoring 1, 8
• Bupropion is present in breast milk and detectable in infant serum, though typically at very low or undetectable levels 1, 8
• Two case reports of seizures in breastfed infants exist, despite generally low transfer into breast milk 1, 8

Infant Monitoring During Breastfeeding

• Monitor for seizures, vomiting, diarrhea, jitteriness, and sedation 1, 8
• Ensure appropriate weight gain and achievement of developmental milestones 1, 8
• Educate the mother on warning signs requiring immediate medical attention, particularly seizure activity, excessive sedation, and poor feeding 8

Important Caveats

• Confounding by indication cannot be ruled out—the underlying depression itself may contribute to observed risks of spontaneous abortion and other adverse outcomes 1, 7
• The absolute risk of cardiovascular defects, even if increased, remains relatively low compared to the risks of untreated maternal depression 1, 4
• Do not abruptly discontinue bupropion when it is required for daily functioning, as untreated maternal depression carries its own significant risks for both mother and fetus 1
• For smoking cessation specifically, the U.S. Preventive Services Task Force reports insufficient evidence to support bupropion's effectiveness or for improving perinatal outcomes in pregnant women 6, 1