What are the potential interactions between Abilify (aripiprazole) and Wellbutrin (bupropion)?

Potential Interactions Between Abilify (Aripiprazole) and Wellbutrin (Bupropion)

The combination of aripiprazole (Abilify) and bupropion (Wellbutrin) can significantly increase aripiprazole exposure by more than five times due to bupropion's inhibition of CYP2D6, requiring careful dose adjustment and monitoring for side effects.

Pharmacokinetic Interaction

• Bupropion is a moderate to strong inhibitor of CYP2D6, one of the main enzymes responsible for aripiprazole metabolism 1
• In preclinical studies, bupropion increased aripiprazole's systemic exposure (AUC) by 5.65-fold and peak concentration (Cmax) by nearly 97% 1
• The active metabolite of aripiprazole (dehydroaripiprazole) also showed increased exposure with a 4-fold increase in AUC and 2-fold increase in Cmax when combined with bupropion 1

Clinical Implications and Management

• Due to this significant pharmacokinetic interaction, aripiprazole dosage should be reduced to approximately 25-50% of the standard dose when used with bupropion 1
• Monitor for increased side effects of aripiprazole, including:
  • Akathisia (restlessness)
  • Insomnia
  • Weight gain
  • Metabolic changes 2

Cardiovascular Considerations

• The combination may increase the risk of cardiovascular side effects:
  • Elevated blood pressure
  • Increased heart rate
  • QTc prolongation 3
• Baseline assessment of blood pressure, heart rate, and ECG is recommended before initiating this combination 3
• Regular monitoring of vital signs is essential, particularly during the first few weeks of combination therapy 3

Seizure Risk

• Bupropion lowers the seizure threshold, with the risk being dose-dependent 4
• The maximum recommended daily dose of bupropion is 450 mg to minimize seizure risk 4
• This combination should be avoided in patients with:
  • History of seizures
  • Brain tumors or metastases
  • Other conditions that lower seizure threshold 3

Other Potential Adverse Effects

• Nausea, dry mouth, jitteriness/agitation, and fatigue have been reported with similar combinations 5
• Insomnia may worsen with this combination, as both medications can cause sleep disturbances 2
• Patients should be monitored for emergence or worsening of suicidal ideation, particularly in young adults under 24 years 4, 6

Dosing Considerations

• For patients with moderate to severe hepatic impairment:
  • Bupropion daily dose should not exceed 150 mg 4
  • Aripiprazole dose should also be reduced 3
• For patients with moderate to severe renal impairment:
  • Bupropion daily dose should be reduced by half 4
  • Adjust aripiprazole accordingly 3

Absolute Contraindications

• This combination is contraindicated in patients with:
  • Current use of MAOIs or within 14 days of stopping MAOIs 4
  • Uncontrolled hypertension 3
  • Severe hepatic impairment 3

Monitoring Recommendations

• Before starting combination:
  • Baseline blood pressure, heart rate, and liver function 3
  • Screen for history of seizures or conditions that lower seizure threshold 3
• During treatment:
  • Regular monitoring of vital signs, especially during initial weeks 3
  • Monitor for emergence of side effects, particularly akathisia, insomnia, and cardiovascular symptoms 2, 5
  • Assess for signs of serotonin syndrome (agitation, hyperthermia, neuromuscular abnormalities) 3

This combination requires careful consideration of risks versus benefits, with close monitoring for adverse effects due to the significant pharmacokinetic interaction that substantially increases aripiprazole exposure.