Is it safe to dose 200mg of Wellbutrin (bupropion) twice a day with Adderall (amphetamine and dextroamphetamine) 5mg twice a day?

Bupropion 200mg BID with Adderall 5mg BID: Dosing Safety and Recommendations

Bupropion should not be dosed at 200mg twice daily (400mg total daily) as this exceeds the maximum recommended dose of 300mg/day for the sustained-release formulation and significantly increases seizure risk. 1, 2

Critical Dosing Limits for Bupropion

The FDA-approved maximum daily dose for bupropion SR is 400mg/day (200mg twice daily), but for bupropion XL it is 450mg/day. 2 However, the standard therapeutic dose for depression is 300mg/day total (150mg twice daily for SR formulation or 300mg once daily for XL formulation). 3, 1

• Seizure risk increases substantially above 450mg/day total dose, with documented seizure incidence of approximately 0.1% at therapeutic doses. 4, 5
• The maximum recommended dose for older adults is 300mg total daily, and doses should be administered in divided doses with the second dose before 3 PM to minimize insomnia. 1, 5

Safety of Combining Bupropion with Adderall

The combination of bupropion with Adderall (amphetamine/dextroamphetamine) is not contraindicated but requires careful monitoring due to additive stimulant effects. 4, 6

Overlapping Pharmacologic Effects

• Both medications increase norepinephrine and dopamine activity, which can lead to additive cardiovascular effects including elevated blood pressure, heart rate, and body temperature. 6
• Bupropion after sustained administration produces effects similar to methylphenidate, including decreased fatigue, increased diastolic blood pressure (67.9 vs 62.5 mm Hg for placebo), elevated body temperature, and weight loss. 6
• Both drugs can impair sleep onset and cause insomnia, particularly if dosed late in the day. 6

Critical Monitoring Requirements

• Monitor blood pressure and heart rate regularly, especially during the first 12 weeks, as both medications can cause elevations. 4, 1
• Avoid this combination in patients with uncontrolled hypertension, as bupropion should not be used in this population. 4, 5
• Watch for increased agitation or activation, as bupropion has activating properties that may be amplified when combined with stimulants. 4, 1

Absolute Contraindications and High-Risk Scenarios

Never use bupropion in patients with:

• Seizure disorders, history of seizures, or any condition that lowers seizure threshold (eating disorders, alcohol withdrawal, abrupt benzodiazepine discontinuation, head trauma, brain metastases, or structural brain lesions). 4, 1, 5
• Current MAOI use or within 14 days of MAOI discontinuation due to hypertensive crisis risk. 4, 2
• Active eating disorders (bulimia or anorexia nervosa) due to significantly increased seizure risk. 1

Recommended Dosing Strategy

If combining bupropion with Adderall 5mg BID, the appropriate bupropion dose is:

• Start bupropion SR at 150mg once daily in the morning for 3-7 days. 1, 2
• Increase to 150mg twice daily (300mg total) if tolerated, with the second dose administered before 3 PM. 1, 5
• Do not exceed 300mg total daily dose when combining with stimulants due to additive cardiovascular and CNS effects. 4, 6

Timing Considerations

• Administer first bupropion dose in the morning and second dose before 3 PM to minimize insomnia risk. 1, 5
• Coordinate Adderall dosing (typically morning and early afternoon) to avoid late-day stimulation. 1

Special Population Adjustments

For patients with hepatic impairment:

• Moderate to severe (Child-Pugh 7-15): Maximum 150mg every other day. 2
• Mild (Child-Pugh 5-6): Consider dose reduction and/or decreased frequency. 2

For patients with renal impairment (GFR <90 mL/min):

• Reduce bupropion dose by 50% and monitor closely for adverse reactions. 1, 2

Clinical Rationale for This Combination

This combination may be beneficial for patients with comorbid depression and ADHD, as bupropion addresses depression through norepinephrine/dopamine pathways while Adderall treats ADHD symptoms. 4, 7 Bupropion has demonstrated equivalent efficacy to methylphenidate for ADHD in controlled trials, though at higher doses (mean 3.3 mg/kg/day). 7

Common Pitfalls to Avoid

• Never exceed 450mg/day total bupropion dose under any circumstances, as seizure risk increases substantially. 5, 2
• Avoid rapid titration of bupropion, which increases seizure and adverse effect risk. 5
• Do not combine with tramadol, meperidine, or other medications that lower seizure threshold. 4
• Never use in patients undergoing abrupt alcohol, benzodiazepine, or antiepileptic drug withdrawal. 1