Bupropion (Wellbutrin) in Pregnancy
Bupropion can be used during pregnancy when clinically indicated, as it does not appear to be associated with major congenital malformations or significant adverse obstetrical outcomes overall, though caution is advised regarding specific cardiovascular defects. 1, 2
Safety Profile During Pregnancy
Overall Malformation Risk
The evidence consistently shows no increased risk for major congenital malformations overall with first-trimester bupropion exposure 1, 2, 3. The FDA label reports that the cardiovascular malformation rate from the international Pregnancy Registry was 1.3% (9/675 first-trimester exposures), which is similar to the background population rate of approximately 1% 2.
Specific Cardiovascular Concerns
Two specific cardiovascular defects warrant attention, though the evidence is inconsistent:
Left Ventricular Outflow Tract Obstruction (LVOTO): The National Birth Defects Prevention Study found increased risk (adjusted OR 2.6; 95% CI 1.2-5.7), with an incidence of 0.279% versus 0.07% with other antidepressants 1. However, other studies including the United Healthcare database did not confirm this association 2.
Ventricular Septal Defects (VSD): One case-control study found elevated risk (adjusted OR 2.9; 95% CI 1.5-5.5, or 2.5 for bupropion monotherapy) 1, 4, but the NBDPS and United Healthcare studies did not find this association 2.
Critical caveat: Confounding by indication (depression itself, smoking cessation needs) cannot be ruled out, and the absolute risks remain small given the rarity of these defects 1, 2.
Other Potential Risks
Diaphragmatic hernia: One study suggested possible increased risk (adjusted OR 2.77; 95% CI 1.34-5.71), but the absolute risk is extremely low given the population prevalence of 0.012%-0.031%, and other studies have not replicated this finding 1.
Spontaneous abortion: Possible increased risk, but confounding by indication cannot be excluded 1.
Poor neonatal adaptation: Only one case report of seizures due to severe hyperinsulinism 1.
Dosing Recommendations
Standard dosing can be maintained during pregnancy 5:
- Sustained Release (SR): Start 100-150 mg daily; maintenance 100-150 mg twice daily
- Extended Release (XL): Start 150 mg daily; maintenance 150-300 mg daily
- Maximum dose: 450 mg per day 1
Important: A 2021 pharmacokinetic study demonstrated no clinically significant changes in bupropion or metabolite concentrations during pregnancy compared to postpartum, indicating dose adjustment during pregnancy is not necessary 5.
Clinical Decision-Making Algorithm
When to Use Bupropion in Pregnancy
Consider bupropion as first-line when:
- Patient requires treatment for moderate-to-severe depression that significantly impacts daily functioning 1
- Patient has co-occurring depression and smoking cessation needs 1
- Patient has failed or cannot tolerate SSRIs/SNRIs
- Patient was stable on bupropion pre-conception
The 2024 AJOG guidelines explicitly state: "Another possibility is switching from stimulants to bupropion (an antidepressant) in the perinatal period, particularly for individuals requiring treatment for co-occurring depression, given the available safety data for this drug in the perinatal period" 1.
Risk-Benefit Discussion Points
Engage patients in shared decision-making covering:
- The consensus that documented risks are very low and treatment should not be stopped if required for daily functioning 1
- Small absolute increases in specific cardiac defects with inconsistent evidence
- Risks of untreated maternal depression (relapse rates are higher when antidepressants are discontinued) 2
- Bupropion is less efficacious than stimulants for ADHD but has better pregnancy safety data 1
Monitoring During Pregnancy
Careful pregnancy monitoring should include 1:
- Fetal growth assessments
- Blood pressure checks
- Ensuring appropriate maternal weight gain
- Consider fetal echocardiography if first-trimester exposure occurred, given the cardiac defect signals (though inconsistent)
Breastfeeding Considerations
Caution is advised during breastfeeding 1:
- Bupropion and metabolites are present in human milk at very low levels (sometimes undetectable)
- Relative infant dose approximately 2% of maternal weight-adjusted dose
- Generally no adverse events reported
- Two case reports of seizures in breastfed infants exist 1
- The 2024 guidelines state: "If taking methylphenidate or bupropion, maintain therapeutic dose at the time of delivery and during breastfeeding" 1
Key Pitfalls to Avoid
Do not automatically discontinue bupropion upon pregnancy discovery if the patient requires it for functioning—the magnitude of documented risks is very low 1
Do not confuse bupropion's ADHD indication with its depression indication—while it can be used for ADHD in pregnancy, it is less efficacious than stimulants 1
Do not overlook drug interactions: Avoid MAOIs (14-day washout required), use caution with other seizure threshold-lowering drugs 2
Do not assume dose escalation is needed—pregnancy does not significantly alter bupropion pharmacokinetics 5
Monitor infant development carefully if breastfeeding—ensure appropriate weight gain and milestone achievement, given the rare seizure reports 1