Can aripiprazole (10 mg) be combined with bupropion (150 or 300 mg)?

Can Aripiprazole 10 mg Be Combined with Bupropion 150 or 300 mg?

Yes, aripiprazole 10 mg can be safely combined with bupropion 150-300 mg, and this combination is supported by clinical evidence for treatment-resistant depression, though you must monitor for a significant drug interaction that increases aripiprazole levels substantially.

Evidence Supporting the Combination

• Aripiprazole augmentation of bupropion is an established strategy for treatment-resistant depression, with case series demonstrating rapid improvement in depressive symptoms when low-dose aripiprazole (2.5-10 mg/day) was added to bupropion therapy 1
• The VAST-D trial, a large randomized study of 1,522 veterans with treatment-resistant depression, directly compared aripiprazole augmentation versus switching to bupropion, confirming both strategies are viable options 2
• Long-term safety data from a 52-week open-label study showed that 47 patients received bupropion plus aripiprazole with no unexpected adverse events, and the combination was well-tolerated with similar efficacy to SSRI/SNRI plus aripiprazole combinations 3

Critical Drug Interaction Warning

Bupropion significantly increases aripiprazole blood levels through CYP2D6 inhibition, which has major clinical implications:

• A preclinical study demonstrated that bupropion increased aripiprazole systemic exposure (AUC) by 5.65-fold and peak concentration (Cmax) by nearly 97% 4
• The exposure to aripiprazole's active metabolite (dehydroaripiprazole) also increased 4-fold 4
• This interaction means you may need to use lower aripiprazole doses than typical when combining with bupropion to avoid excessive drug levels and side effects 4

Practical Dosing Recommendations

Start with aripiprazole 2.5-5 mg daily when combining with bupropion, rather than the standard 10 mg starting dose:

• Case series showed effective antidepressant responses with aripiprazole doses of 2.5-10 mg/day when added to bupropion 150-450 mg/day 1
• If you're already using aripiprazole 10 mg, this dose is acceptable but monitor closely for side effects given the drug interaction 1
• For bupropion, use standard depression dosing: 150 mg twice daily (300 mg total) is the typical therapeutic target 5

Safety Monitoring Requirements

Watch for aripiprazole-related side effects more carefully due to increased drug levels:

• Akathisia is the most common concern—one patient in the case series developed akathisia that resolved with dose reduction 1
• Monitor for weight gain and metabolic effects (glucose, lipids), which occurred in both treatment groups in the 52-week study 3
• Screen for tardive dyskinesia risk, particularly important given higher aripiprazole exposure 6
• Monitor for insomnia worsening, as both medications can be activating 1
• Check blood pressure regularly, as bupropion can elevate BP 5, 7

Absolute Contraindications to Screen For

Before combining these medications, ensure the patient does NOT have:

• Active seizure disorder or seizure history—bupropion lowers seizure threshold with 0.1% risk at 300 mg/day 5, 7
• Eating disorders (bulimia/anorexia)—increases seizure risk with bupropion 5
• Current MAOI use or within 14 days of stopping MAOIs—risk of hypertensive crisis 7
• Uncontrolled hypertension—bupropion can worsen this 5, 7
• Moderate to severe hepatic impairment—reduce bupropion to maximum 150 mg daily 5
• Moderate to severe renal impairment—reduce bupropion dose by 50% 5

Timing and Administration

Optimize timing to minimize side effects:

• Give bupropion SR 150 mg in the morning and second dose before 3 PM to reduce insomnia risk 5
• Aripiprazole can be given once daily, typically in the morning 1
• Allow 6-8 weeks at therapeutic doses before assessing adequacy of response 5, 7

When This Combination Is Particularly Beneficial

Consider this combination specifically for patients with:

• Treatment-resistant depression who failed adequate bupropion monotherapy 1
• Depression with prominent low energy, apathy, or hypersomnia—bupropion's activating properties help 5
• Patients aged ≥65 years with treatment-resistant depression—VAST-D trial showed aripiprazole augmentation was more effective than switching to bupropion in this age group 2
• Patients with severe mixed hypomanic symptoms—augmentation strategies outperformed switching 2

Comparative Effectiveness Considerations

A 2025 risk-benefit analysis provides important context:

• In adults under 65 years, combination therapy with bupropion (adding it to another antidepressant) was preferred over aripiprazole augmentation when accounting for metabolic risks and tardive dyskinesia 6
• Aripiprazole augmentation offered only 8.0 depression-free day-equivalents after subtracting TD harms, and this became negative (-22.8 days) in overweight patients due to metabolic effects 6
• However, this analysis compared different treatment strategies; your question asks about combining both medications, which is a distinct approach 6

Common Pitfalls to Avoid

• Don't use standard aripiprazole starting doses without considering the interaction—start lower at 2.5-5 mg given the 5-fold increase in exposure 4
• Don't exceed bupropion 300 mg/day for depression to maintain seizure risk at 0.1% 5
• Don't discontinue abruptly—taper gradually to minimize withdrawal symptoms 5
• Don't forget to monitor metabolic parameters—fasting glucose and lipids should be checked, as 17.4% of patients on SSRI/SNRI plus aripiprazole developed abnormal fasting glucose in the 52-week study 3