What is the efficacy of Wellbutrin (bupropion) for treating Attention Deficit Disorder (ADD)?

Efficacy of Wellbutrin (Bupropion) for ADD/ADHD

Bupropion (Wellbutrin) is a second-line treatment for ADHD with moderate efficacy (effect size approximately 0.7) compared to stimulants (effect size approximately 1.0), and should be considered when stimulants are contraindicated, not tolerated, or ineffective. 1

Treatment Hierarchy for ADHD

The American Academy of Pediatrics recommends the following treatment approach for ADHD:

1. First-line medications: Stimulants (methylphenidate, amphetamine derivatives)

   • Superior efficacy with effect size of approximately 1.0 1
   • Considered standard of care due to robust evidence base

2. FDA-approved non-stimulants:

   • Atomoxetine (Strattera)
   • Extended-release guanfacine (Intuniv)
   • Extended-release clonidine (Kapvay)
   • Effect sizes in the medium range (approximately 0.7) 1

3. Off-label options (including bupropion)

   • Used when first and second-line treatments are ineffective or contraindicated

Bupropion's Efficacy for ADHD

Bupropion has demonstrated efficacy for ADHD in multiple studies:

• A Cochrane systematic review found low-quality evidence that bupropion decreased ADHD symptom severity (standardized mean difference -0.50) and increased the proportion of adults achieving clinical improvement (RR 1.50) compared to placebo 2

• In a 6-week double-blind, placebo-controlled trial, bupropion showed significant improvement in ADHD symptoms compared to placebo 3

• A multisite study of bupropion XL demonstrated that 53% of patients responded to bupropion compared to 31% for placebo, with an effect size of 0.6 4

• Bupropion appears to provide sustained benefit throughout the day (morning, afternoon, and evening) 4

Comparative Efficacy

• Bupropion has shown efficacy comparable to methylphenidate in some head-to-head trials, but a large multicenter study found smaller effect sizes for bupropion compared to methylphenidate 5

• The effect size of bupropion (approximately 0.6-0.7) is lower than stimulants (approximately 1.0) but similar to other non-stimulant options 1, 4

Special Populations and Considerations

• Bupropion may be particularly useful in patients with:
  • Comorbid depression 5
  • Substance use disorders (improves ADHD symptoms but has limited effect on substance use) 6
  • Contraindications to stimulants

Practical Prescribing Information

• Dosing:

  • Starting dose: 150 mg sustained-release daily
  • Target dose: 300-450 mg daily (divided doses) 4
  • Titration: Increase gradually over several weeks

• Monitoring:

  • Efficacy: ADHD symptom reduction
  • Side effects: Headache, insomnia, dry mouth, nausea
  • Blood pressure and heart rate

Important Caveats

• Bupropion is not FDA-approved for ADHD treatment (off-label use)
• Evidence quality is generally low to moderate 2
• Long-term efficacy data is limited 2
• Response may be less robust than with stimulant medications 1
• Contraindicated in patients with seizure disorders or eating disorders

Clinical Decision Algorithm

1. Try FDA-approved stimulants first (methylphenidate or amphetamine derivatives)
2. If ineffective or not tolerated, try FDA-approved non-stimulants (atomoxetine, guanfacine, clonidine)
3. Consider bupropion if:
   • Previous options ineffective/not tolerated
   • Comorbid depression exists
   • Concern about stimulant misuse potential
   • Patient preference after discussing efficacy differences