Is it safe to take Wellbutrin (bupropion) and Modafinil together?

Concurrent Use of Wellbutrin (Bupropion) and Modafinil

Taking Wellbutrin (bupropion) and modafinil together requires caution due to potential drug interactions that could increase the risk of seizures and other adverse effects. 1, 2

Drug Information and Mechanisms

• Bupropion (Wellbutrin) is a dopamine/norepinephrine reuptake inhibitor approved for depression and smoking cessation 1
• Modafinil is a wakefulness-promoting agent approved for excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and shift-work sleep disorder 2, 3
• Both medications affect dopaminergic and noradrenergic pathways in the brain, potentially creating overlapping effects 4

Potential Interactions and Risks

Seizure Risk

• Bupropion is known to lower the seizure threshold, with two case reports of seizures in breastfed infants exposed to bupropion 1
• When combined with modafinil, which can cause nervousness and insomnia, the risk of seizures may be increased 2, 3

Cardiovascular Effects

• Both medications can potentially increase blood pressure and heart rate 1, 2
• The combination may amplify these cardiovascular effects 3

Central Nervous System Effects

• Overlapping side effects include:
  • Insomnia and sleep disturbances 2, 3
  • Headache 2
  • Nervousness and anxiety 2
  • Potential for mood changes 3

Pharmacokinetic Interactions

• Modafinil induces and inhibits several cytochrome P450 isoenzymes, creating potential for drug interactions 3
• Bupropion is listed as having interactions with modafinil in clinical guidelines 1

Dosing Considerations

• Modafinil's maximum daily dose is 400 mg, typically administered as a single morning dose or divided into two doses 2
• Bupropion SR maintenance dose is typically 100-150 mg twice daily, with a maximum of 450 mg per day 1
• If the combination is deemed necessary, consider starting with lower doses of both medications and monitoring closely 2

Monitoring Recommendations

• Monitor for:
  • Seizure activity or lowered seizure threshold 1
  • Blood pressure and heart rate changes 1, 2
  • Sleep disturbances 2, 3
  • Mood changes, anxiety, or agitation 3
  • Signs of serotonin syndrome (although rare with this combination) 5

Special Populations

• Pregnancy: Both medications have limited data in pregnancy, with bupropion showing possible risk for cardiovascular malformations 1
• Hepatic impairment: Doses of both medications should be reduced 3
• Elderly patients: Start with lower doses, particularly modafinil (100 mg) 2

Clinical Perspective

• While there are case reports of using these medications together for conditions like narcolepsy with depression 6, the combination is not well-studied
• The risk-benefit ratio must be carefully considered, especially in patients with:
  • History of seizures 1
  • Cardiovascular disease 1, 2
  • Substance use disorders (both medications have some abuse potential) 3, 7

Alternative Approaches

• For depression with fatigue, consider alternative antidepressants with less seizure risk 5
• For ADHD, atomoxetine is FDA-approved as a non-stimulant option 4
• For narcolepsy or excessive sleepiness, consider modafinil alone before adding bupropion 3

In conclusion, while the combination of bupropion and modafinil is not absolutely contraindicated, it should be approached with caution due to the potential for increased adverse effects, particularly seizure risk. Close monitoring is essential if this combination is used.