Are bupropion (Wellbutrin) and atomoxetine (Strattera) safe to use during pregnancy?

Safety of Wellbutrin and Strattera in Pregnancy

Both bupropion (Wellbutrin) and atomoxetine (Strattera) appear reasonably safe during pregnancy, with no substantial increase in major congenital malformations or adverse long-term neurodevelopmental outcomes, though data remain limited and caution is advised. 1

Atomoxetine (Strattera) Safety Profile

Congenital Malformations

• Atomoxetine does not appear to be associated with major congenital malformations, including cardiac malformations. 1
• A large multinational study of nearly 1,000 first-trimester exposures found no increased risk of major congenital malformations overall (adjusted PR 0.99,95% CI 0.74-1.34). 2
• For cardiac malformations specifically, the adjusted prevalence ratio was 1.34 (95% CI 0.86-2.09), which was not statistically significant. 2
• A 2024 meta-analysis involving over 16 million pregnancies found no increased risk of congenital anomalies (OR 1.14,95% CI 0.83-1.55). 3

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion exists, but confounding by indication (the underlying ADHD itself) cannot be ruled out. 1
• Meta-analysis showed no significant increase in miscarriages (OR 1.01,95% CI 0.70-1.47). 3

Long-Term Neurodevelopmental Outcomes

• A recent large, well-controlled study demonstrated no increased risks for neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment. 1

FDA Labeling

• The FDA label states atomoxetine should not be used during pregnancy "unless the potential benefit justifies the potential risk to the fetus" (Pregnancy Category C). 4

Bupropion (Wellbutrin) Safety Profile

Congenital Malformations

• Bupropion does not appear to be associated with major congenital malformations overall, though data are limited. 1
• A small absolute increase in two specific cardiovascular malformations has been reported with first-trimester bupropion monotherapy, but confounding by indication cannot be ruled out and other studies have not consistently found these associations. 1

The two specific cardiac defects include:

• Left ventricular outflow tract obstruction heart defects (incidence 0.279% vs 0.07% with other antidepressants). 1
• Ventricular septal defects (aOR 2.9,95% CI 1.5-5.5). 1
  • One case-control study found an elevated risk of VSD with bupropion alone (aOR 2.5,95% CI 1.3-5.0). 5

Other Potential Risks

• Possible increased risk for diaphragmatic hernia (aOR 2.77,95% CI 1.34-5.71) in one study, though the absolute risk is extremely small given the rarity of this condition (population prevalence 0.012%-0.031%), and other studies have not found this association. 1

Obstetrical Outcomes

• Possible increased risk for spontaneous abortion. 1
• Possible increased risk for poor neonatal adaptation, though this has been reported in only one case (presenting with seizures due to prolonged hypoglycemia from severe hyperinsulinism). 1

Long-Term Outcomes

• Further research is needed to clarify a possible increased risk for ADHD in offspring and to disentangle likely confounding by indication. 1
• A systematic review found pooled estimates for congenital malformations of 1.0% (95% CI 0.0%-3.0%), mean birthweight of 3305.9g, and mean gestational age of 39.2 weeks—all within normal ranges. 6

Clinical Decision-Making Algorithm

When to Consider Continuing Medication:

1. Severe ADHD symptoms that significantly impair maternal functioning or safety
2. History of severe decompensation when medication was discontinued
3. Comorbid depression requiring treatment (particularly relevant for bupropion)
4. Smoking cessation needs during pregnancy (bupropion indication)

Risk Counseling Points:

• For atomoxetine: Reassure that large studies show no increased risk of major malformations or long-term neurodevelopmental problems. 1, 3, 2
• For bupropion: Discuss the small potential increase in specific cardiac defects (VSD, left ventricular outflow tract obstruction), emphasizing that absolute risks remain low and confounding cannot be excluded. 1, 5
• Both medications: Acknowledge possible increased spontaneous abortion risk, though this may be related to underlying ADHD rather than medication. 1

Common Pitfalls to Avoid:

• Do not assume all cardiac defects are equally elevated with bupropion—only specific defects (VSD and left ventricular outflow tract obstruction) show potential associations. 1, 5
• Do not discontinue medication abruptly without considering maternal risks—untreated ADHD itself may pose risks to pregnancy through impaired self-care, accidents, or comorbid conditions. 7
• Do not overlook confounding by indication—women taking these medications may have underlying conditions that independently affect pregnancy outcomes. 1, 3

Monitoring Recommendations:

• Consider detailed fetal cardiac ultrasound at 18-22 weeks if bupropion was used in the first trimester, given the potential (though uncertain) association with cardiac defects. 1, 5
• Monitor for signs of poor neonatal adaptation at delivery, particularly with bupropion exposure. 1