What is the half-life and dosage timeline of Wellbutrin (bupropion) XL for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Bupropion XL Pharmacokinetics and ADHD Dosing

Half-Life and Metabolism

While the provided evidence does not contain specific half-life data for bupropion XL, the American College of Obstetricians and Gynecologists guidelines indicate that bupropion has a long half-life sufficient to allow once-daily dosing with the XL formulation. 1

Dosing Protocol for ADHD

Start bupropion XL at 150 mg orally once daily, then titrate to a maintenance dose of 150-300 mg daily, with a maximum of 450 mg per day. 1, 2

Specific Dosing Timeline:

• Week 1: Begin with 150 mg XL once daily in the morning 1, 2
• Week 2-3: May increase to 300 mg once daily if needed for symptom control 1, 2
• Maximum dose: 450 mg per day (though most patients respond to 150-300 mg) 1, 2

Timeline for ADHD Symptom Relief

Expect initial response within 2 weeks, with full therapeutic effect by 6-8 weeks of treatment. 3

• Significant improvement over placebo can be observed as early as week 2 of treatment 3
• By week 6-8, approximately 53% of patients achieve response (defined as ≥30% reduction in ADHD symptoms) compared to 31% with placebo 3
• The effect size for ADHD symptom reduction is 0.6, which is moderate 3

Critical Considerations for ADHD Treatment

Bupropion requires daily dosing to maintain therapeutic levels—unlike stimulants, it cannot be used intermittently or "as needed." 2

Position in Treatment Algorithm:

• Bupropion is NOT first-line therapy for ADHD 2
• Stimulants (methylphenidate, amphetamines) should be tried first 1
• Second-line options include atomoxetine, guanfacine, or clonidine before bupropion 2
• Bupropion is particularly useful when:
  • Co-occurring depression exists 2
  • Stimulants are contraindicated or not tolerated 2
  • Active substance use disorders are present 4

Efficacy Profile:

• Bupropion provides sustained benefit throughout the day (morning, afternoon, and evening) 3
• In head-to-head comparison, bupropion showed equivalent efficacy to methylphenidate in one pediatric study, though this finding requires cautious interpretation given limited replication 5
• Bupropion is less efficacious than stimulants for core ADHD symptoms 2

Important Safety Warnings

Do not combine bupropion with stimulants without extreme caution—no safety studies exist for this combination. 2

• Bupropion is generally well-tolerated with low discontinuation rates (5%) 3
• The maximum dose of 450 mg/day should never be exceeded due to seizure risk 1, 2
• Monitor for activation of mania in patients with bipolar disorder, though bupropion appears relatively safe in this population when mood stabilizers are used concurrently 6