Can a patient with Attention Deficit Hyperactivity Disorder (ADHD) or depression be on Wellbutrin (bupropion) and Strattera (atomoxetine) concurrently?

Can a Patient Be on Wellbutrin and Strattera Concurrently?

Yes, a patient can safely be on Wellbutrin (bupropion) and Strattera (atomoxetine) concurrently, as this combination is well-tolerated and addresses ADHD through complementary mechanisms without significant drug interactions. 1

Evidence Supporting Concurrent Use

The combination of atomoxetine and bupropion has been studied in clinical practice, with research demonstrating that:

• Combined therapy with atomoxetine and another antidepressant (fluoxetine) was well-tolerated in pediatric patients with ADHD and comorbid symptoms, with completion rates and discontinuation rates for adverse events similar to monotherapy 1

• Both medications work through different mechanisms: atomoxetine is a selective norepinephrine reuptake inhibitor, while bupropion works via noradrenergic/dopaminergic pathways, providing complementary therapeutic effects 2, 3

• Bupropion has demonstrated efficacy for ADHD symptoms with low-quality evidence showing decreased severity of ADHD symptoms (standardized mean difference -0.50) and increased clinical improvement rates (RR 1.50) 2

Clinical Advantages of This Combination

This combination may be particularly beneficial when:

• The patient has ADHD with comorbid depression, as bupropion addresses depressive symptoms while atomoxetine targets ADHD core symptoms 2, 3

• The patient requires non-stimulant ADHD treatment due to stimulant intolerance, abuse concerns, or inadequate response 2, 3

• The patient experiences low energy or apathy, as bupropion has activating properties that can improve these symptoms 4

Critical Safety Monitoring Required

Cardiovascular Monitoring

• Monitor blood pressure and heart rate at baseline and periodically during treatment, especially in the first 12 weeks, as both medications can cause elevations 4, 1
• The combination group showed greater increases in blood pressure and pulse than monotherapy in clinical trials, though these were generally well-tolerated 1

Seizure Risk Assessment

• Confirm the patient has no history of seizures or conditions predisposing to seizures before initiating bupropion, as it lowers seizure threshold 4, 2
• Maximum bupropion dose should not exceed 450 mg/day to maintain seizure risk at 0.1% 4
• Avoid bupropion in patients with eating disorders (bulimia/anorexia), brain tumors, or those abruptly discontinuing alcohol, benzodiazepines, or antiepileptic drugs 4

Psychiatric Monitoring

• Monitor for neuropsychiatric adverse effects including agitation, restlessness, and behavioral changes, particularly in patients under 24 years old who require close monitoring for suicidal ideation 4
• Assess mental status within 1-2 weeks of initiation, as the risk for suicide attempts is greatest during the first 1-2 months of treatment 4

Dosing Recommendations for Combination Therapy

Atomoxetine Dosing

• Start with 40 mg daily, titrating every 7-14 days to 60 mg then 80 mg as tolerated 5
• Maximum dose is the lesser of 1.4 mg/kg/day or 100 mg/day 5

Bupropion Dosing

• For depression: Start with 150 mg SR once daily for 3 days, then increase to 150 mg twice daily (300 mg total) 4
• For ADHD augmentation: Consider starting at 37.5 mg every morning, increasing by 37.5 mg every 3 days as tolerated, with maximum 300 mg/day 4
• Administer the second dose before 3 PM to minimize insomnia risk 4

Absolute Contraindications to This Combination

Do not use this combination if the patient has:

• Current seizure disorder or history of seizures (bupropion contraindication) 4, 2
• Uncontrolled hypertension (both medications can elevate blood pressure) 4
• Current or recent MAOI use (within 14 days) (bupropion contraindication) 4
• Eating disorders (bulimia or anorexia nervosa) (bupropion contraindication) 4
• Moderate to severe hepatic impairment without dose adjustment (both medications require dose reduction) 4

Drug Interaction Considerations

• Bupropion is a moderate CYP2D6 inhibitor, which can increase plasma concentrations of medications metabolized by this enzyme, including certain beta-blockers (metoprolol, propranolol, carvedilol) 6
• If the patient is on beta-blockers, monitor closely for hypotension, bradycardia, and falls when initiating bupropion 6
• Atomoxetine does not have significant CYP2D6 inhibitory effects, so the primary concern is with bupropion's interactions 1

Expected Timeline for Clinical Response

• Begin monitoring therapeutic response and adverse effects within 1-2 weeks of initiating the combination 4
• Allow 6-8 weeks at adequate doses before determining treatment response for depression and ADHD symptoms 4
• Energy levels may improve more rapidly with bupropion, sometimes within the first few weeks 4

Common Pitfalls to Avoid

• Do not exceed maximum bupropion doses (450 mg/day for XL, 400 mg/day for SR) to prevent seizure risk 4
• Do not administer bupropion doses late in the day, as this increases insomnia risk 4
• Do not abruptly discontinue either medication without tapering, particularly if the patient has been on treatment for extended periods 4
• Do not assume generic formulations are bioequivalent—monitor closely when switching between brand and generic bupropion formulations 4