Can Wellbutrin (bupropion) be used as an alternative to Qelbree (viloxazine) to manage Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents?

Can Wellbutrin Be Used as an Alternative to Qelbree for ADHD Management?

Wellbutrin (bupropion) can be used as an alternative to Qelbree (viloxazine) for ADHD management, but both are second-line agents that should only be considered after FDA-approved first-line medications (stimulants and atomoxetine) have failed or are contraindicated. 1

Treatment Hierarchy for ADHD in Children and Adolescents

First-Line Treatment (Ages 6-18)

• Stimulant medications remain the gold standard, with evidence particularly strong for methylphenidate and amphetamines, achieving 70-80% response rates and the largest effect sizes from over 161 randomized controlled trials 1, 2
• For elementary school-aged children (6-11 years), FDA-approved medications should be prescribed, with evidence particularly strong for stimulants and sufficient but less strong for atomoxetine, extended-release guanfacine, and extended-release clonidine (in that order) 1
• For adolescents (12-18 years), FDA-approved medications should be prescribed with the assent of the adolescent 1

Second-Line Treatment: When to Consider Bupropion

Bupropion should be considered only when:

• Two or more stimulants have failed or caused intolerable side effects 2
• Active substance abuse disorder is present (though atomoxetine or alpha-2 agonists are preferred in this scenario) 1, 2
• Comorbid depression exists alongside ADHD, though even here the evidence suggests treating ADHD with stimulants first, then adding an SSRI if depressive symptoms persist 2

Evidence for Bupropion in ADHD

Efficacy Data

• A Cochrane systematic review found low-quality evidence that bupropion decreased ADHD symptom severity (standardized mean difference -0.50) and increased the proportion achieving clinical improvement (risk ratio 1.50) compared to placebo 3
• Head-to-head trials in children found bupropion had comparable efficacy to methylphenidate, though a large multicenter study found smaller effect sizes for bupropion than methylphenidate when using teacher and parent ratings 4, 5, 6
• Effect sizes of bupropion/placebo differences were somewhat smaller than for standard stimulant drugs 6

Clinical Considerations for Bupropion

• Dosing: 100-150 mg daily for children <30 kg; 150 mg daily for children >30 kg; adults can be titrated to 100-150 mg twice daily (SR) or 150-300 mg daily (XL), with maximum 450 mg per day 2, 4, 5
• Onset of action: Works more rapidly than atomoxetine (which requires 6-12 weeks) but slower than stimulants (which work within days) 1, 2
• Tolerability: Generally well-tolerated, with headache, insomnia, and anxiety as potential side effects 2, 6
• Seizure risk: Increases at higher doses, particularly when combined with stimulants 2

Evidence for Viloxazine (Qelbree)

• Viloxazine is a repurposed antidepressant classified as a serotonin norepinephrine modulating agent that has completed several pivotal clinical trials in children showing favorable efficacy and tolerability 2
• It has demonstrated efficacy in adults with ADHD 2
• As a newer medication, viloxazine has less extensive long-term safety data compared to bupropion

Critical Decision Algorithm

Step 1: Have FDA-approved first-line medications been adequately trialed?

• If NO → Trial stimulants (methylphenidate or amphetamines) first 1
• If stimulants are contraindicated → Consider atomoxetine (60-100 mg daily for adults) as it has stronger evidence than bupropion 1, 2

Step 2: Are there specific comorbidities that favor one agent?

• Comorbid depression + ADHD: Bupropion may address both, though evidence shows no single antidepressant effectively treats both conditions; preferred approach is stimulant + SSRI if needed 2, 7
• Comorbid anxiety: Avoid bupropion due to its activating properties; consider atomoxetine or alpha-2 agonists instead 1, 2
• Substance abuse history: Atomoxetine or alpha-2 agonists preferred over bupropion due to no abuse potential 1, 2

Step 3: If choosing between bupropion and viloxazine specifically:

• Bupropion advantages: Longer track record, more clinical experience, may help with comorbid depression, promotes weight loss 2, 3
• Viloxazine advantages: Newer data showing favorable tolerability, may have fewer activating side effects than bupropion 2

Common Pitfalls to Avoid

• Do not assume bupropion will effectively treat both ADHD and depression as a single agent; evidence specifically states no single antidepressant is proven for this dual purpose 2
• Do not use bupropion as first-line when stimulants have not been adequately trialed, as stimulants have significantly larger effect sizes 1, 2, 3
• Do not prescribe bupropion for patients with prominent hyperactivity or anxiety as its activating properties can worsen these symptoms 2
• Avoid concurrent use with MAO inhibitors due to risk of hypertensive crisis; at least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion 2
• Monitor closely for seizures when using bupropion, especially at higher doses or in combination with stimulants 2

Monitoring Requirements

When using bupropion for ADHD:

• Monitor blood pressure and pulse at baseline and regularly during treatment 1, 2
• Track height and weight, particularly in younger patients 1
• Screen for suicidality and clinical worsening, especially when comorbid depression exists 1, 2
• Assess for worsening hyperactivity, insomnia, anxiety, and agitation during the first 2-4 weeks 2