What are the guidelines for combining Bupropion (Wellbutrin) and Aripiprazole (Abilify)?

Guidelines for Combining Bupropion (Wellbutrin) and Aripiprazole (Abilify)

The combination of bupropion (Wellbutrin) and aripiprazole (Abilify) can be effective for treatment-resistant depression, but requires careful monitoring due to significant drug interactions that increase aripiprazole exposure by more than five times in preclinical studies.

Pharmacokinetic Interaction

• Bupropion is a moderate to strong CYP2D6 enzyme inhibitor 1
• Aripiprazole is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes 1
• When combined, bupropion significantly increases aripiprazole exposure:
  • 5.65-fold increase in AUC (area under the curve)
  • 96.76% increase in maximum concentration (Cmax)
  • 9-fold decrease in systemic clearance 1
  • 4-fold increase in exposure to dehydroaripiprazole (active metabolite) 1

Clinical Efficacy

• Adjunctive aripiprazole in low doses (2.5-10 mg/day) has shown rapid improvement in depressive symptoms in patients with bupropion-resistant major depression 2
• All patients in a small case series reported sustained antidepressant effects for at least 4 months, though mood disturbance returned in 2 of 4 patients 2
• The combination has also shown promise in treating bipolar disorder type I with comorbid cocaine dependence 3

Dosing Recommendations

• When combining these medications:
  • Start with lower doses of aripiprazole (2.5-5 mg/day) due to the significant pharmacokinetic interaction 2, 1
  • Standard bupropion dosing ranges from 150-450 mg/day 2
  • Monitor closely for side effects and adjust doses accordingly

Safety Concerns and Monitoring

Side Effects to Monitor

• Seizure risk: Both medications can lower seizure threshold

  • Bupropion has an estimated seizure risk of 0.4% at recommended doses 4
  • Use with extreme caution in patients with seizure history or risk factors 4

• Movement disorders: Monitor for akathisia, which may respond to lowering aripiprazole dose 2

• Sleep disturbances: Insomnia may worsen with this combination 2

  • The American Academy of Family Physicians recommends taking bupropion in the morning, and if a second dose is required, taking it before 3 PM to minimize sleep problems 5

• Metabolic parameters: Regular monitoring of weight and metabolic parameters is recommended 2

Contraindications

• Absolute contraindications for this combination:

  • Seizure disorders 5, 4
  • Current use of MAO inhibitors (requires 14-day washout period) 5
  • Severe agitation 5

• Use with caution in patients with:

  • Liver or kidney dysfunction 5
  • Advanced age 5
  • History of seizures or risk factors 5, 4
  • Cardiovascular disease 5

Practical Approach to Combination Therapy

1. Initial assessment: Evaluate seizure risk factors and contraindications
2. Starting regimen:
   • Begin with established bupropion dose (150-450 mg/day)
   • Add low-dose aripiprazole (2.5 mg/day) and titrate slowly
3. Monitoring schedule:
   • Weekly for first month to assess for akathisia, insomnia, and other side effects
   • Adjust aripiprazole dose based on response and tolerability
4. Long-term follow-up:
   • Regular assessment of continued efficacy
   • Monitor for return of depressive symptoms, which may occur despite initial response 2

This combination shows promise for treatment-resistant depression but requires careful management of the significant pharmacokinetic interaction to maximize benefits while minimizing risks.