What are the risks and recommendations for a pregnant female patient taking Wellbutrin (bupropion) for depression or smoking cessation?

Wellbutrin (Bupropion) and Pregnancy

Primary Recommendation

Behavioral interventions should be the first-line treatment for smoking cessation in pregnant women, as they have proven substantial benefit without risk. 1 For depression treatment during pregnancy, bupropion may be continued if already established on therapy, but requires careful risk-benefit discussion given small absolute increases in specific cardiac defects. 2, 3

Evidence-Based Treatment Algorithm

For Smoking Cessation in Pregnancy

Step 1: Behavioral Interventions (Strongly Recommended)

• Behavioral counseling, health education, incentives, and social support substantially improve smoking cessation rates (15.2% vs 11.2% in controls), increase birthweight (mean difference 40.78g), and decrease preterm birth with no harms. 1
• This is the only intervention with high-certainty evidence of substantial net benefit in pregnancy. 1

Step 2: Pharmacotherapy Consideration (Insufficient Evidence)

• The USPSTF concludes that current evidence on pharmacotherapy (including bupropion) for smoking cessation in pregnant women is insufficient. 1
• No studies have evaluated bupropion specifically for smoking cessation during pregnancy. 1
• Given insufficient evidence and established safety of behavioral interventions, pharmacotherapy should not be first-line. 1

For Depression Treatment in Pregnancy

If Patient is Already Taking Bupropion Before Pregnancy:

• Engage in risk-benefit discussion regarding continuing at current effective dose versus switching to alternatives. 2, 3
• The benefits of treating maternal depression may outweigh the small absolute increased risks in many clinical scenarios. 2, 3

If Considering Starting Bupropion During Pregnancy:

• Bupropion does not increase overall major congenital malformations above baseline. 2, 3, 4, 5
• However, first-trimester exposure carries specific risks that must be weighed carefully (see below). 2, 3

Specific Risks with First-Trimester Exposure

Cardiac Malformations (Small Absolute Risk Increase)

• Left ventricular outflow tract obstruction and ventricular septal defects: adjusted OR 2.9 (95% CI 1.5-5.5). 2, 3
• Despite elevated odds ratio, absolute risk remains relatively low given baseline rarity of these conditions. 2
• The FDA label notes that study findings on left ventricular outflow tract obstruction are inconsistent and do not allow definitive conclusions. 4

Other Potential Risks

• Diaphragmatic hernia: adjusted OR 2.77 (95% CI 1.34-5.71), though absolute risk is extremely small (population prevalence 0.012%-0.031%). 2, 3
• Possible increased risk for spontaneous abortion. 2, 3, 5
• One prospective study found significantly more spontaneous abortions in the bupropion group (P = 0.009). 5

Monitoring During Pregnancy

If continuing or starting bupropion, monitor carefully for:

• Fetal growth parameters. 2, 3
• Maternal blood pressure. 2, 3
• Appropriate maternal weight gain. 2, 3

Breastfeeding Considerations

Bupropion can be used cautiously during breastfeeding, but requires vigilant infant monitoring:

• Bupropion is present in human milk and detected in infant serum, though typically at very low or undetectable levels. 3, 6
• Two case reports document seizures in breastfed infants despite generally low drug transfer. 3, 6
• The American Academy of Pediatrics recommends maintaining therapeutic dose while breastfeeding with careful monitoring for seizures, vomiting, diarrhea, jitteriness, and sedation. 3, 6
• Monitor infant weight gain and developmental milestones. 3, 6

Critical Caveats and Pitfalls

Confounding by Indication

• The underlying conditions (depression or smoking) may themselves contribute to observed risks, making it difficult to isolate medication effects. 3
• Untreated maternal depression carries its own risks to mother and fetus. 4

Contraindications in Pregnancy

• All bupropion-containing products for weight management are absolutely contraindicated in pregnancy. 2
• Bupropion is contraindicated in patients with seizure risks (including brain metastases), those taking MAO inhibitors, or those with closed-angle glaucoma. 1, 4

Limited Efficacy Data in Pregnancy

• One small randomized trial (n=65) showed bupropion reduced cravings and withdrawal symptoms during treatment but found no significant difference in abstinence rates at end of pregnancy (10% vs 3%, P=0.328). 7
• Trial feasibility is challenging due to restrictive eligibility criteria needed for safety concerns. 8

Neuropsychiatric Monitoring

• Although uncommon, monitor for development or worsening of depression and suicidal ideation/behavior, and discontinue if these occur. 1, 4
• Recent multicenter RCT found neuropsychiatric adverse events with bupropion were not significantly increased relative to placebo in both psychiatric and non-psychiatric cohorts. 1