What is the recommended dose of Wellbutrin (bupropion) for treating depression and motivation issues in combination with Adderall (amphetamine and dextroamphetamine) for Attention Deficit Hyperactivity Disorder (ADHD)?

Wellbutrin Dosing for Depression and Motivation Combined with Adderall

Start with Adderall optimization first, then add bupropion SR 100-150 mg daily (or XL 150 mg daily) if ADHD symptoms improve but depression and motivation problems persist, titrating to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL), with a maximum of 450 mg per day. 1

Treatment Algorithm

Step 1: Optimize Stimulant Therapy First

• Begin with Adderall (or continue current dose) as the primary treatment for ADHD, as stimulants work rapidly and have 70-80% response rates for ADHD symptoms 1
• Typical Adderall dosing ranges from 10-50 mg daily when used in combination therapy 1
• Assess response within days to weeks, as stimulants provide quick feedback on efficacy 1
• The reduction in ADHD-related functional impairment from stimulants alone may indirectly improve depressive symptoms and motivation 1

Step 2: Add Bupropion if Needed

• If ADHD symptoms respond to Adderall but depression and motivation problems remain severe, add bupropion to the regimen 2, 1
• Start bupropion SR at 100-150 mg once daily or XL at 150 mg once daily 1
• Titrate to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL) 1
• Maximum dose is 450 mg per day 1
• This combination allows addressing both conditions without discontinuing effective ADHD treatment 1

Step 3: Monitor for Efficacy and Safety

• The combination of bupropion and stimulants may enhance ADHD symptom control, particularly when stimulants alone provide inadequate response 1
• Bupropion decreases ADHD symptom severity (effect size -0.50) and increases clinical improvement rates (50% greater than placebo) 3
• In one double-blind crossover trial, bupropion at mean dose 3.3 mg/kg per day showed equivalent efficacy to methylphenidate for ADHD symptoms 4

Critical Safety Considerations

Drug Interactions

• There are no specific warnings against combining bupropion with stimulants in FDA labeling, but careful monitoring is essential 1
• The combination may increase seizure risk, particularly at higher bupropion doses (risk increases above 450 mg/day) 1
• Unlike tricyclic antidepressants, no significant pharmacokinetic interactions occur between bupropion and stimulants 2

Common Side Effects to Monitor

• Bupropion commonly causes headache, insomnia, and anxiety 1
• When combined with stimulants, monitor for additive effects on appetite suppression, insomnia, and anxiety 1
• The tolerability of bupropion is generally similar to placebo in clinical trials 3

Substance Abuse Considerations

• Exercise caution when prescribing stimulants to patients with comorbid substance abuse disorders 2, 1
• If substance abuse history is present, consider long-acting stimulant formulations with lower abuse potential 1
• Bupropion may be preferred as monotherapy in active substance abuse, though stimulants remain more effective for ADHD 1

Important Clinical Pitfalls to Avoid

• Do not assume bupropion alone will effectively treat both ADHD and depression—no single antidepressant is proven for this dual purpose 1
• Bupropion and tricyclic antidepressants are second-line agents at best for ADHD treatment compared to stimulants 2, 1
• Do not use MAO inhibitors concurrently with either bupropion or stimulants due to risk of hypertensive crisis 2, 1
• Avoid treating severe major depressive disorder with psychosis or suicidality by adding medications to stimulants—address the depression as primary in these cases 2

Evidence Quality Note

The evidence supporting bupropion for ADHD is low quality due to small sample sizes and short study durations (6-10 weeks), with uncertainty regarding long-term outcomes 3. However, the combination approach is supported by guideline recommendations prioritizing stimulant optimization followed by adjunctive treatment for residual symptoms 1.