What formulation of bupropion (Bupropion) is recommended for treating Attention Deficit Hyperactivity Disorder (ADHD), extended release or short acting?

Bupropion Extended Release (XL/SR) Formulation is Preferred for ADHD Treatment

For treating ADHD, the extended release formulation of bupropion (XL or SR) is recommended over immediate release due to better adherence, sustained efficacy throughout the day, and reduced frequency of administration. 1

Formulation Options and Dosing

Extended Release (XL) Formulation

• Starting dose: 150 mg once daily 2
• Maintenance dose: 150-300 mg once daily 2
• Maximum dose: 450 mg per day 2
• Advantages:
  • Once-daily dosing improves adherence
  • Provides sustained coverage throughout the day 1
  • Reduced peak-trough fluctuations 3
  • Better privacy for adolescents (no need for school dosing) 2

Sustained Release (SR) Formulation

• Starting dose: 100-150 mg once daily 2
• Maintenance dose: 100-150 mg twice daily 2
• Advantages:
  • Twice-daily dosing still preferable to three times daily IR
  • Bioequivalent to XL in terms of systemic exposure 4

Immediate Release (IR) Formulation

• Not recommended for ADHD due to:
  • Requires three times daily dosing 4
  • More frequent peak-trough fluctuations
  • Higher risk of adherence issues

Evidence Supporting Extended Release Formulations

Research specifically examining bupropion XL in adults with ADHD demonstrated:

• 53% response rate compared to 31% for placebo (p=0.004) 1
• Treatment effect size of 0.6 on ADHD Rating Scale 1
• Sustained benefit throughout the day (morning, afternoon, and evening) 1
• Low discontinuation rate (5%) due to adverse events 1

Clinical Considerations

Efficacy Across the Day

Extended release formulations provide more consistent blood levels, which is particularly important for ADHD symptoms that need management throughout the day 1. The XL formulation has a longer absorption phase (Tmax ~5 hours) compared to IR (Tmax ~1.5 hours) and SR (Tmax ~3 hours) 3.

Patient Populations

• Adolescents: Extended release formulations are particularly beneficial for adolescents to maintain privacy at school by avoiding mid-day dosing 2
• Adults with comorbid substance use disorders: Bupropion SR has shown 43% reduction in ADHD symptoms in this population 5

Safety Profile

All bupropion formulations have similar safety profiles, but extended release formulations may reduce peak-related side effects:

• Common side effects: headache, dry mouth, nausea, insomnia, constipation, and dizziness 6
• Lower incidence of sexual dysfunction, weight gain, and somnolence compared to many other antidepressants 6
• Seizure risk is dose-dependent; extended release formulations may help manage this risk through more gradual absorption 6

Important Cautions

• Seizure threshold: All bupropion formulations lower the seizure threshold; avoid in patients with seizure disorders 6
• Drug interactions: Bupropion inhibits CYP2D6 and may reduce clearance of medications metabolized by this enzyme 3
• Cardiovascular effects: Monitor for potential increases in blood pressure

Alternative Options

If bupropion is not suitable, atomoxetine is an appropriate alternative non-stimulant for ADHD with a different mechanism of action 7. Atomoxetine is dosed at 40 mg daily initially, titrated to 60-80 mg/day with a maximum of 1.4 mg/kg/day or 100 mg/day 7.

In summary, when choosing between bupropion formulations for ADHD treatment, extended release (XL) is the preferred option due to once-daily dosing, sustained efficacy throughout the day, and improved adherence. If XL is not available, sustained release (SR) is the next best option.