Is Wellbutrin (bupropion) safe to use during pregnancy in an adult female with a history of depression?

Wellbutrin (Bupropion) Safety in Pregnancy

Bupropion can be used during pregnancy when clinically necessary for depression, as it does not increase the overall risk of major congenital malformations above baseline, though there is a small absolute increased risk of specific cardiac defects that must be weighed against the substantial risks of untreated maternal depression. 1

Overall Malformation Risk

• Bupropion does not appear to increase the risk of major congenital malformations overall based on data from the International Bupropion Pregnancy Registry (675 first-trimester exposures) and retrospective cohort studies (1,213 first-trimester exposures). 1

• The FDA label explicitly states that epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall. 1

• Meta-analysis found the pooled estimated proportion of congenital malformations among live-born infants was only 1.0% (95% CI = 0.0%-3.0%), which is within the general population baseline of 2-4%. 2

Specific Cardiac Defects - The Key Caveat

While overall malformation risk is not elevated, there is a small absolute increased risk of two specific cardiovascular defects with first-trimester exposure:

• Left ventricular outflow tract obstruction (LVOTO) heart defects, though study findings are inconsistent and do not allow definitive conclusions. 3, 4, 1

• Ventricular septal defects (VSD) with an adjusted odds ratio of 2.9 (95% CI, 1.5-5.5). 3, 5

• The prospectively observed rate of cardiovascular malformations from the International Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester exposures), which is similar to the background rate of approximately 1%. 1

• Critical point: The absolute risk remains low despite the elevated odds ratio, and confounding by indication (the underlying depression or smoking) cannot be ruled out. 4, 5, 6

Other Potential Risks

• Possible increased risk for diaphragmatic hernia (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%. 3, 4, 5

• Possible increased risk for spontaneous abortion, though this finding is consistent with other antidepressants and may reflect the underlying condition rather than the medication. 3, 4, 5, 7

• One case report of poor neonatal adaptation with seizures due to prolonged hypoglycemia from severe hyperinsulinism. 3, 5

Clinical Decision-Making Algorithm

When a pregnant woman with depression is taking or considering bupropion:

1. Engage in a risk-benefit discussion regarding continuing at the current well-tolerated, effective dose versus considering alternatives. 3, 4, 5

2. Weigh the risks of untreated maternal depression, which include increased risk of relapse (women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than those who continued). 1

3. Consider bupropion as a reasonable option, particularly when the patient also requires smoking cessation support or has not responded to other antidepressants. 3, 6

4. If continuing bupropion, monitor pregnancy carefully including fetal growth, maternal blood pressure checks, and appropriate weight gain. 3, 4, 5

5. Maintain the therapeutic dose rather than reducing it ineffectively, as the benefits of adequately treating maternal depression likely outweigh the small absolute increased risks. 3, 5

Birth Outcomes

• Mean birth weight following bupropion exposure was 3305.9 g (95% CI = 3173.2-3438.7 g), which is normal. 2

• Mean gestational age at delivery was 39.2 weeks (95% CI = 38.8-39.6 weeks), indicating no increased risk of preterm birth. 2

• No evidence of increased risk for low birth weight or premature delivery. 2

Important Clinical Caveats

The magnitude of documented risks is very low and should not automatically preclude use. 3 The American Journal of Obstetrics and Gynecology guidelines emphasize that treatment with medications should not be stopped if they are required for the daily functioning of the pregnant person. 3

Confounding by indication is a major limitation in interpreting the cardiac defect data - the underlying depression, smoking, or other factors may contribute to observed risks rather than the medication itself. 4, 5, 6

Untreated maternal depression carries substantial risks including poor prenatal care, inadequate nutrition, substance use, and adverse neonatal outcomes, which must be weighed against the small absolute increased risk of specific cardiac defects. 1