What is the preferred formulation of Wellbutrin (bupropion) XL or IR for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)?

Bupropion XL for ADHD in Adults

For adults with ADHD, bupropion XL (extended-release) is the preferred formulation over IR (immediate-release) due to superior adherence, sustained symptom control throughout the day, and once-daily dosing convenience. 1

Formulation Selection

• Bupropion XL provides sustained benefit throughout the entire day (morning, afternoon, and evening symptom control) compared to placebo, making it the optimal choice for consistent ADHD management 1
• The extended-release formulation allows for once-daily dosing up to 450 mg/day, which significantly improves medication adherence compared to multiple daily doses required with IR formulations 1
• IR formulations are not studied or recommended for ADHD treatment in adults, as all clinical trials demonstrating efficacy have used long-acting bupropion formulations 1, 2

Dosing Protocol for Bupropion XL

• Start with 150 mg once daily in the morning 3
• Titrate to maintenance dose of 150-300 mg daily based on response and tolerability 3
• Maximum dose is 450 mg per day 3, 1
• Allow adequate time between dose adjustments to properly evaluate response before escalating 4

Evidence for Efficacy

• Bupropion XL demonstrated 53% responder rate (≥30% symptom reduction) versus 31% with placebo at 8 weeks, with significant improvement as early as week 2 1
• The treatment effect size was 0.6, indicating moderate clinical benefit 1
• Low-quality evidence from systematic review shows bupropion decreases ADHD symptom severity and increases clinical improvement rates (RR 1.50,95% CI 1.13-1.99) 2

Position in Treatment Algorithm

• Bupropion is a second-line, non-stimulant alternative when stimulants (methylphenidate or amphetamines) are contraindicated, not tolerated, or ineffective 3, 4
• Stimulants remain first-line treatment for adult ADHD due to superior efficacy and rapid onset 3, 4
• Consider bupropion as first-line in specific populations: active substance use disorders, comorbid depression, or smoking cessation needs 5, 6

Safety and Tolerability

• Bupropion XL was safe and well-tolerated with only 5% discontinuation rate due to adverse effects 1
• Tolerability is similar to placebo based on withdrawal rates (RR 1.20,95% CI 0.35-4.10) 2
• Do not combine bupropion with stimulants until further safety data are available 4
• Screen for seizure risk factors, as bupropion lowers seizure threshold 3

Critical Pitfalls to Avoid

• Never use IR formulations for ADHD - no evidence base exists and multiple daily dosing reduces adherence 1, 2
• Do not expect immediate response - bupropion requires 2-6 weeks for full therapeutic effect, unlike stimulants which work within hours 2, 5
• Avoid in patients with eating disorders, seizure history, or abrupt alcohol/benzodiazepine withdrawal due to increased seizure risk 3

Special Populations

• Bupropion may be particularly useful in adults with ADHD plus comorbid substance use disorders, showing 43% reduction in ADHD symptoms without worsening substance use 5
• In ADHD with comorbid bipolar disorder, bupropion SR reduced ADHD symptoms by 55% without significant mood destabilization when combined with mood stabilizers 6