Is Wellbutrin (bupropion) safe to use with amphetamine?

Safety of Combining Wellbutrin (Bupropion) with Amphetamine

Combining Wellbutrin (bupropion) with amphetamine is generally not recommended due to increased risk of seizures, cardiovascular complications, and neuropsychiatric effects.

Pharmacological Considerations

Bupropion and amphetamines have overlapping mechanisms of action that can lead to potentially dangerous interactions:

• Both medications affect dopaminergic and noradrenergic neurotransmission
• Bupropion is a substituted cathinone (β-keto amphetamine) that inhibits norepinephrine/dopamine reuptake 1
• The combination can lead to excessive stimulation of the central nervous system

Seizure Risk

The most significant concern with this combination is the increased risk of seizures:

• Bupropion alone carries a seizure risk of approximately 0.1% at therapeutic doses 2
• This risk increases with higher doses and when combined with other medications that lower the seizure threshold
• There have been documented cases of seizures in breastfed infants exposed to bupropion 3
• The FDA recommends caution when using medications that may lower seizure threshold in patients with risk factors

Cardiovascular Risks

The combination presents significant cardiovascular concerns:

• Both medications can increase blood pressure and heart rate
• Bupropion can cause cardiotoxicity in overdose situations 1
• Amphetamines are known to cause cardiovascular adverse events including tachycardia and arrhythmia
• The combination may potentiate these effects, leading to potentially dangerous cardiovascular complications

Neuropsychiatric Effects

Mental health impacts are also a concern:

• Both medications can cause insomnia, anxiety, and agitation
• The combination may exacerbate these effects
• Bupropion carries a boxed warning about serious neuropsychiatric events 2
• Patients with pre-existing psychiatric conditions may be at higher risk

Alternative Approaches

For patients requiring treatment for both depression and ADHD:

1. Sequential approach: Treat the more severe condition first, then address the secondary condition
2. Alternative medications: Consider non-stimulant options for ADHD (e.g., atomoxetine) or alternative antidepressants
3. Dose optimization: If combination therapy is absolutely necessary, use the lowest effective doses of both medications with careful monitoring

Special Populations

Pregnancy and Breastfeeding

• Bupropion during pregnancy may be associated with a small increased risk of cardiovascular malformations 2
• There have been case reports of seizures in breastfed infants exposed to bupropion 3
• The American College of Obstetricians and Gynecologists recommends caution when prescribing amphetamines to breastfeeding mothers 3

Patients with Seizure Risk

• Avoid this combination in patients with:
  • Personal or family history of seizures
  • History of head trauma
  • Concurrent use of other medications that lower seizure threshold
  • Substance use disorders

Monitoring Recommendations

If this combination must be used despite risks:

• Start with low doses and titrate slowly
• Monitor vital signs regularly, particularly blood pressure and heart rate
• Watch for warning signs of seizure activity
• Conduct regular assessments for neuropsychiatric symptoms
• Consider electrocardiogram monitoring for patients with cardiovascular risk factors

Conclusion

While there may be individual cases where the benefits of combining these medications outweigh the risks, the potential for serious adverse effects generally makes this combination inadvisable. Alternative treatment strategies should be strongly considered before resorting to concurrent use of bupropion and amphetamine.