Can you combine Wellbutrin (bupropion) with Adderall (amphetamine and dextroamphetamine)?

Combining Wellbutrin (Bupropion) with Adderall (Amphetamine/Dextroamphetamine)

The combination of Wellbutrin (bupropion) and Adderall (amphetamine/dextroamphetamine) should be used with caution due to increased seizure risk, but can be considered in specific clinical scenarios when benefits outweigh risks. 1

Safety Considerations

Seizure Risk

• Bupropion reduces the seizure threshold with a documented 0.1% seizure risk at therapeutic doses 1
• This risk may be compounded when combined with stimulants like Adderall
• Contraindicated in patients with:
  • History of seizures
  • Brain lesions or structural abnormalities
  • Alcohol abuse 1

Cardiovascular Effects

• Both medications can increase blood pressure and heart rate
• Combination may exacerbate these effects
• Avoid in patients with uncontrolled hypertension or significant cardiovascular disease 1

Evidence for Combination Use

While there are no specific studies examining the bupropion-Adderall combination, clinical guidelines provide some insight:

• The American Academy of Child and Adolescent Psychiatry notes: "There are no studies of the combination of bupropion and stimulants in the treatment of ADHD or other psychiatric conditions" but also states that "clinicians should proceed with caution in combining these agents until further studies are available" 2

• Both medications have been studied separately for ADHD:

  • Bupropion has shown efficacy comparable to methylphenidate in some studies 3
  • This suggests potential utility in patients who cannot tolerate or have contraindications to stimulants

Clinical Decision Algorithm

1. First-line approach: Use either medication alone before considering combination

   • Try optimizing the dose of a single agent first

2. Consider combination when:

   • Partial response to either medication alone
   • Need for augmentation in treatment-resistant depression with comorbid ADHD
   • Need for smoking cessation (bupropion benefit) in a patient requiring ADHD treatment

3. Absolute contraindications:

   • History of seizures
   • Current alcohol/substance abuse
   • Severe eating disorders
   • Uncontrolled hypertension

4. Monitoring requirements:

   • Baseline vital signs and neurological assessment
   • Regular monitoring of blood pressure, heart rate
   • Observe for neuropsychiatric symptoms
   • Monitor for insomnia, which may be exacerbated by both medications

Dosing Considerations

• Start with lower doses of both medications when using in combination
• Titrate slowly with close monitoring
• Consider timing of doses to minimize insomnia:
  • Bupropion SR: First dose in morning, second dose in early afternoon 1
  • Adderall: Earlier in day to minimize sleep disruption

Common Side Effects of Combination

• Insomnia (increased risk with both medications)
• Dry mouth
• Anxiety/jitteriness
• Decreased appetite
• Headache
• Potential for increased blood pressure and heart rate

Important Caveats

• The combination may increase risk of serotonin syndrome when other serotonergic medications are added 4
• Bupropion inhibits CYP2D6, which could potentially affect metabolism of amphetamines
• The combination has been used clinically despite limited research, but requires careful monitoring

When considering this combination, the primary goal should be optimizing treatment for the underlying conditions while minimizing risks, particularly focusing on seizure risk as the most significant safety concern.