Can bupropion (antidepressant) be used to treat Attention Deficit Hyperactivity Disorder (ADHD)?

Bupropion for ADHD

Bupropion can be used as a second-line treatment for ADHD when stimulants are ineffective, cause intolerable side effects, or when there are concerns about stimulant misuse, but stimulants remain the first-line treatment with superior efficacy. 1

Treatment Hierarchy

First-Line Treatment

• Stimulant medications (methylphenidate and amphetamine-based stimulants) are the gold standard for ADHD treatment, with 70-80% response rates. 2, 1
• Stimulants work rapidly, allowing assessment of ADHD symptom response within days. 2
• Methylphenidate is recommended at 5-20 mg three times daily for adults, while dextroamphetamine is dosed at 5 mg three times daily to 20 mg twice daily. 2

Second-Line: When to Consider Bupropion

Bupropion should be considered in the following clinical scenarios:

• When stimulants are ineffective or cause intolerable side effects 1
• When there are concerns about stimulant misuse or diversion 1
• In patients with comorbid depression where dual treatment may be beneficial 2
• In patients with substance abuse history where stimulants pose higher risk 2

Bupropion Efficacy Evidence

Symptom Improvement

• Bupropion decreases ADHD symptom severity with a standardized mean difference of -0.50 (95% CI -0.86 to -0.15), though this is based on low-quality evidence. 3
• The proportion of patients achieving clinical improvement increases by 50% compared to placebo (RR 1.50,95% CI 1.13 to 1.99). 3
• Clinical Global Impression-Improvement scores show 78% greater improvement with bupropion versus placebo (RR 1.78,95% CI 1.27 to 2.50). 3
• Head-to-head trials found bupropion had comparable efficacy to methylphenidate, though one large multicenter study found smaller effect sizes for bupropion than methylphenidate. 4

Comparative Effectiveness

While bupropion shows benefit, its effect sizes are smaller than stimulants, making it clearly a second-line option. 1, 4

Dosing Protocol

Sustained-Release (SR) Formulation

• Start at 100-150 mg daily 1
• Titrate to maintenance dose of 100-150 mg twice daily 1
• Titration should be gradual to minimize side effects 1

Extended-Release (XL) Formulation

• Start at 150 mg daily 1
• Titrate to maintenance dose of 150-300 mg daily 1
• Maximum dose: 450 mg daily 2, 1

Safety Considerations

Common Side Effects

• Headache, insomnia, and anxiety are notable side effects. 2
• The proportion of patients withdrawing due to adverse effects is similar between bupropion and placebo (RR 1.20,95% CI 0.35 to 4.10), indicating tolerability comparable to placebo. 3

Serious Risks

• Seizure risk increases, particularly at higher doses, and this risk is further elevated when combined with stimulants. 2
• Bupropion has a narrow therapeutic window with maximum daily dosing of 450 mg. 5
• Cardiotoxicity including QT prolongation can occur in overdose situations. 5

Drug Interactions

• Never use MAO inhibitors concurrently with bupropion due to risk of severe hypertension and potential cerebrovascular accidents. 2
• When combining with stimulants, careful monitoring for side effects is necessary, though no specific FDA warnings exist against this combination. 2

Special Populations

Pregnancy

• Bupropion may be considered as an alternative to stimulants during pregnancy, though it has been associated with a small increased risk of certain cardiovascular malformations with first-trimester exposure. 2
• Limited data suggests bupropion does not appear to be associated with major congenital malformations. 1

Substance Abuse History

• Bupropion is particularly useful in patients with substance abuse history where stimulants pose diversion or misuse concerns. 2, 1
• Long-acting stimulant formulations like Concerta may still be preferred over bupropion in this population due to lower abuse potential. 2

Comorbid Bipolar Disorder

• Bupropion may be effective for ADHD in adults with comorbid bipolar disorder without significant activation of mania, though this requires adjunct mood stabilizers. 6

Combination Therapy

Adding bupropion to stimulant medication may enhance ADHD symptom control when stimulants alone are inadequate, particularly when comorbid depressive symptoms exist. 2

• Start bupropion SR at 100-150 mg daily or XL at 150 mg daily when adding to existing stimulant therapy 2
• Monitor carefully for increased seizure risk with combination therapy 2

Critical Pitfall to Avoid

Do not assume bupropion will effectively treat both ADHD and depression simultaneously—no single antidepressant is proven for this dual purpose. 2 If ADHD symptoms improve on stimulants but mood symptoms persist, consider adding an SSRI to the stimulant regimen rather than switching to bupropion monotherapy. 2