What is the recommended dosing for Wellbutrin (bupropion) in Attention Deficit Hyperactivity Disorder (ADHD)?

Wellbutrin (Bupropion) Dosing for ADHD

Bupropion is a second-line medication for ADHD that should only be considered after stimulants (methylphenidate or amphetamines) have failed, are not tolerated, or are contraindicated due to substance abuse history. 1

When to Consider Bupropion

Bupropion should be reserved for specific clinical scenarios rather than as first-line treatment:

• After stimulant failure: Try all three stimulant classes (methylphenidate, dextroamphetamine, and mixed amphetamine salts) before switching to bupropion, as stimulants have 70-80% response rates compared to bupropion's more modest efficacy 2, 1
• Active substance use disorder: Bupropion avoids the abuse potential of stimulants while still addressing ADHD symptoms 1, 3
• Comorbid depression with ADHD: When both conditions require treatment, though stimulants plus SSRIs remain preferred over bupropion monotherapy 1
• Stimulant intolerance: When patients cannot tolerate stimulant side effects like anxiety, insomnia, or cardiovascular effects 4

Specific Dosing Regimens

Extended-Release (XL) Formulation

• Starting dose: 150 mg once daily in the morning 5
• Titration: Increase to 300 mg once daily after 3-7 days if tolerated 5
• Maximum dose: 450 mg once daily 5
• Time to effect: Full therapeutic benefit requires 2-4 weeks, unlike stimulants which work within hours 1

Sustained-Release (SR) Formulation

• Starting dose: 100 mg once daily 3
• Titration: Increase weekly to target dose of 200 mg twice daily (400 mg total daily) 3
• Dosing schedule: Administer doses at least 8 hours apart to minimize seizure risk 3

Expected Efficacy

The evidence for bupropion in ADHD shows moderate effectiveness:

• Response rate: Approximately 53% of patients achieve ≥30% reduction in ADHD symptoms versus 31% with placebo 5
• Effect size: 0.5-0.6, which is substantially lower than stimulants' effect sizes of 0.9-1.0 4, 5
• Symptom coverage: Provides sustained benefit throughout morning, afternoon, and evening when using XL formulation 5
• ADHD with substance use disorder: Reduces ADHD symptoms by 43% but has negligible effects on substance use itself 3

Critical Safety Considerations

Seizure Risk

• Maximum single dose: Never exceed 150 mg for immediate-release, 200 mg for SR, or 450 mg for XL formulations to minimize seizure risk 5
• Contraindications: Avoid in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/benzodiazepines 4

Monitoring Requirements

• Baseline assessment: Screen for suicidality, particularly when comorbid depression exists 1
• Cardiovascular monitoring: Check blood pressure and pulse, though effects are less pronounced than with stimulants 1
• Psychiatric monitoring: Watch for worsening anxiety, agitation, or insomnia, especially in first 2-4 weeks 1

Common Pitfalls to Avoid

• Using bupropion as first-line: This deprives patients of the most effective treatment (stimulants) with the strongest evidence base 1
• Expecting rapid response: Unlike stimulants that work within hours, bupropion requires weeks to months for full effect 1
• Assuming it treats both ADHD and depression equally: No single antidepressant is proven to effectively treat both conditions simultaneously; combination therapy (stimulant + SSRI) is preferred 1
• Combining with MAO inhibitors: This combination risks hypertensive crisis; allow at least 14 days between discontinuing an MAOI and starting bupropion 1
• Using in patients with prominent hyperactivity or anxiety: Bupropion's activating properties can exacerbate these symptoms 1

Comparative Effectiveness

In head-to-head comparison, bupropion (mean 3.3 mg/kg/day) produced equivalent improvement to methylphenidate (mean 0.7 mg/kg/day) on multiple ADHD rating scales in a pediatric crossover trial 6. However, this single small study (n=15) contrasts with the broader evidence base showing stimulants as superior first-line agents 1.

Special Population: Adults

For adults with ADHD, the American Academy of Child and Adolescent Psychiatry recommends methylphenidate 5-20 mg three times daily or dextroamphetamine 5 mg three times daily to 20 mg twice daily as first-line treatment 2. Bupropion should be considered only after these options have been exhausted 1.