Is it safe to use Wellbutrin (bupropion) and Strattera (atomoxetine) together?

Safety of Combining Wellbutrin (Bupropion) and Strattera (Atomoxetine)

The combination of Wellbutrin (bupropion) and Strattera (atomoxetine) should be used with caution due to potential increased risks of seizures, cardiovascular effects, and neuropsychiatric symptoms, but may be appropriate in specific clinical scenarios with careful monitoring.

Mechanism of Action and Potential Interactions

• Bupropion: Acts as a dopamine/norepinephrine reuptake inhibitor 1
• Atomoxetine: Functions as a selective norepinephrine reuptake inhibitor 2
• Combined effect: Both medications affect norepinephrine pathways, potentially leading to additive effects

Safety Concerns with Combination Therapy

Seizure Risk

• Bupropion carries a dose-dependent seizure risk (approximately 0.1% at therapeutic doses) 3
• Risk increases when combined with other medications that affect neurotransmitters
• Patients with history of seizures, head trauma, or substance use disorders are at higher risk 3

Cardiovascular Effects

• Both medications can affect cardiovascular parameters:
  • Atomoxetine: Associated with statistically significant increases in heart rate and blood pressure 2
  • Bupropion: Can cause increased blood pressure 4, 5
  • Combined effect may potentially amplify these cardiovascular changes

Neuropsychiatric Effects

• Both medications carry black box warnings for suicidal ideation/behavior 1, 2
• Bupropion may trigger manic episodes, particularly at higher doses (>450 mg/day) 6
• Atomoxetine has been associated with rare but serious liver injury 2

Monitoring Recommendations

If combination therapy is deemed necessary:

1. Start with low doses and titrate slowly

   • Begin with lower doses of each medication than would be used in monotherapy
   • Increase doses gradually while monitoring for side effects

2. Regular monitoring of vital signs

   • Check blood pressure and heart rate at baseline and regularly during treatment
   • Consider more frequent monitoring in patients with pre-existing cardiovascular conditions

3. Watch for warning signs of seizure activity

   • Educate patients about warning signs and when to seek emergency care
   • Monitor closely during the first 30 days of treatment when seizure risk is highest

4. Regular assessment for neuropsychiatric symptoms

   • Monitor for signs of suicidal ideation, especially in younger patients
   • Watch for symptoms of mania, particularly with higher bupropion doses

Special Populations and Considerations

Patients with Increased Risk

• Avoid combination in patients with:
  • History of seizures or seizure disorders
  • Eating disorders (increased seizure risk)
  • Uncontrolled hypertension
  • Severe hepatic impairment

Drug Interactions

• Consider potential interactions with other medications:
  • CYP2D6 inhibitors (like paroxetine) can increase atomoxetine levels 2
  • MAO inhibitors are contraindicated with both medications 1

Alternative Approaches

If the combination poses too high a risk:

1. Optimize monotherapy first

   • Ensure adequate trial of one medication at therapeutic dose before adding another
   • Consider extended-release formulations for better tolerability

2. Consider alternative combinations

   • SSRIs with either medication may have lower risk profiles for some patients
   • Non-pharmacological interventions (therapy, lifestyle modifications) as adjuncts

Conclusion

While the combination of bupropion and atomoxetine is not absolutely contraindicated, it requires careful consideration of risk-benefit ratio, appropriate patient selection, close monitoring, and dose optimization to minimize potential adverse effects.