Is bupropion (Wellbutrin) safe to use during the first trimester (approximately 3 months) of pregnancy?

Bupropion (Wellbutrin) Use in the First Trimester of Pregnancy

Bupropion can be used during the first trimester of pregnancy when clinically necessary, as it does not appear to increase the overall risk of major congenital malformations, though caution is advised regarding specific cardiovascular defects.

Overall Safety Profile

According to the most recent 2024 guidelines from the American Journal of Obstetrics and Gynecology, bupropion does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes overall, although data are limited 1. This is corroborated by FDA labeling data showing that epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall 2.

The International Bupropion Pregnancy Registry (675 first-trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first-trimester exposures) both found no increased risk for malformations overall 2.

Specific Cardiovascular Concerns

While overall malformation risk is not elevated, there is conflicting evidence regarding two specific cardiovascular defects:

Left Ventricular Outflow Tract Obstruction (LVOTO)

• One study (National Birth Defects Prevention Study) found increased risk: adjusted OR 2.6 (95% CI 1.2-5.7) 2, 3
• However, the Slone Epidemiology case-control study did not find increased risk for LVOTO 2
• The absolute incidence remains very low (0.279% vs 0.07% with other antidepressants) 1

Ventricular Septal Defects (VSD)

• The Slone Epidemiology Study found increased risk: adjusted OR 2.5 (95% CI 1.3-5.0), particularly with bupropion monotherapy (adjusted OR 2.9; 95% CI 1.5-5.5) 1, 4
• However, the National Birth Defects Prevention Study and United Healthcare database did not find this association 2

Important caveat: These findings are limited by small numbers of exposed cases, inconsistent results across studies, and potential confounding by indication (depression itself or smoking cessation indication) 1, 2.

Other Potential Risks

• Spontaneous abortion: Possible increased risk, but confounding by indication cannot be ruled out 1, 5
• Diaphragmatic hernia: One study suggested possible increased risk (adjusted OR 2.77; 95% CI 1.34-5.71), but the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%), and other studies have not confirmed this 1
• Poor neonatal adaptation: Reported in only one case (seizures from hypoglycemia) 1

Clinical Decision-Making Algorithm

When bupropion is required for daily functioning:

1. Do NOT discontinue if the medication is necessary for the pregnant person's functioning 1

   • The consensus is that documented risks are very low and treatment should not be stopped if required 1
   • Untreated depression carries its own risks to mother and fetus 2

2. Consider these strategies:

   • Use the lowest effective dose 1
   • Consider intermittent use (as-needed basis) to maximize functioning while reducing fetal exposure 1
   • Particularly appropriate for co-occurring depression and smoking cessation 1

3. Monitoring during pregnancy:

   • Careful pregnancy monitoring including fetal growth 1
   • Blood pressure checks 1
   • Ensure appropriate maternal weight gain 1
   • Consider fetal echocardiography if concerned about cardiac defects

4. Preconception counseling:

   • Engage in risk-benefit discussion regarding medication choice and lowest effective dose 1
   • If medication is not likely to severely impact daily functioning, consider trial of gradual discontinuation before pregnancy 1

Important Context

The 2024 guidelines emphasize that bupropion is less efficacious than stimulants for ADHD treatment but may be a reasonable alternative in the perinatal period, particularly for individuals requiring treatment for co-occurring depression, given the available safety data 1.

The magnitude of documented risks is arguably not clinically meaningful, and evidence suggests these risks may be elevated in depression/ADHD in general rather than being directly attributable to the medication 1.