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

Wellbutrin and Abilify Combination Therapy

Yes, Wellbutrin (bupropion) and Abilify (aripiprazole) can be safely taken together and this combination is commonly used in clinical practice, particularly for bipolar depression and treatment-resistant depression. 1

Safety Profile

The combination of bupropion and aripiprazole is explicitly endorsed by major medical organizations:

• The American Academy of Family Physicians recommends this combination as a standard treatment approach, particularly when patients have not responded adequately to initial antidepressant monotherapy 1
• This represents a well-established "next-step" treatment strategy for depression that has proven resistant to single-agent therapy 2, 3

Critical Safety Considerations

Seizure Risk (Primary Concern)

Bupropion is the main concern in this combination due to seizure risk:

• Bupropion lowers the seizure threshold and must not exceed 300 mg per day to minimize seizure risk 1
• Aripiprazole (quetiapine was mentioned in error in one source) does not significantly increase seizure risk 1
• Absolute contraindications include active seizure disorder, conditions lowering seizure threshold, or brain metastases 1

Cardiovascular Monitoring

Both medications can affect cardiovascular parameters:

• Monitor blood pressure and heart rate, particularly in patients with cardiovascular disease or hypertension 1
• Baseline and periodic vital signs are mandatory 1

Absolute Contraindications

Do not use this combination if the patient has: 1

• Active seizure disorder or conditions lowering seizure threshold
• Uncontrolled hypertension
• Concurrent MAO inhibitor use (within 14 days)
• Pregnancy or active attempts to conceive

Required Monitoring Protocol

Implement the following monitoring schedule: 1

• Baseline vital signs before initiation
• Periodic vital signs throughout treatment
• Watch for signs of serotonin syndrome
• Monitor for neuropsychiatric effects including suicidal ideation (particularly in first 12 weeks)
• Assess for any seizure activity, especially during dose escalation

Recommended Dosing Algorithm

For bupropion: 1

• Start at 150 mg once daily
• Increase to 150 mg twice daily after 3-7 days if tolerated
• Maximum dose: 300 mg/day (never exceed this)

For aripiprazole:

• Standard augmentation dosing applies (typically 2-15 mg daily based on indication)

Clinical Effectiveness

This combination demonstrates superior efficacy compared to monotherapy:

• In the VAST-D trial of 1,522 patients with treatment-resistant depression, augmentation with aripiprazole was one of three effective next-step strategies 2, 3
• Approximately two-thirds of patients who don't respond to initial antidepressant treatment require such next-step approaches 3
• Specific populations benefit most: patients ≥65 years old show better response to aripiprazole augmentation compared to switching strategies alone 3
• Patients with severe mixed hypomanic symptoms respond particularly well to aripiprazole augmentation 3

Common Adverse Effects to Anticipate

Expect and counsel patients about: 1

• Insomnia (dose bupropion earlier in day, not late afternoon/evening)
• Neuropsychiatric effects requiring close monitoring
• Potential metabolic effects from aripiprazole (though lower risk than other antipsychotics)
• Extrapyramidal symptoms possible with long-term aripiprazole use 4

Special Clinical Scenarios

This combination is particularly useful for:

• Bipolar depression (where aripiprazole provides mood stabilization) 4
• Treatment-resistant unipolar depression 2, 3
• Patients with comorbid anxiety (aripiprazole-mood stabilizer combinations show promise) 4
• Patients requiring smoking cessation support (bupropion provides dual benefit, though seizure vigilance increases) 5

Critical Pitfall to Avoid

Never combine bupropion with clozapine - this dramatically increases seizure risk, as both agents lower seizure threshold and may have synergistic rather than merely additive effects 5. The combination discussed here (bupropion + aripiprazole) does not carry this same compounded risk since aripiprazole does not lower seizure threshold 1.