Bupropion for ADHD Treatment
Bupropion can be used to treat ADHD in adults, but it is a second-line agent—stimulant medications (methylphenidate or amphetamines) should be tried first due to their superior efficacy, with 70-80% response rates compared to bupropion's more modest effect sizes. 1, 2
Position in Treatment Algorithm
Stimulants remain the gold standard first-line treatment for ADHD, with the largest effect sizes and most robust evidence base from over 161 randomized controlled trials. 3, 2
Bupropion should be considered as a second-line option when: 2, 4
- Stimulants are contraindicated or not tolerated
- Patient has comorbid depression requiring treatment
- Patient has a history of substance abuse (bupropion is not a controlled substance)
- Patient has concerns about stimulant misuse or diversion
The American Academy of Child and Adolescent Psychiatry explicitly states that no single antidepressant, including bupropion, is proven to effectively treat both ADHD and depression simultaneously—if both conditions require treatment, combination therapy is typically needed. 1
Evidence for Bupropion's Efficacy
A Cochrane systematic review found low-quality evidence that bupropion decreased ADHD symptom severity (standardized mean difference -0.50) and increased the proportion of patients achieving clinical improvement (risk ratio 1.50) compared to placebo. 5
Head-to-head trials in children found bupropion had comparable efficacy to methylphenidate, though a large multicenter study showed smaller effect sizes for bupropion than methylphenidate based on teacher and parent ratings. 4
A randomized, double-blind study in adults demonstrated significant improvement in ADHD symptoms after 6 weeks of bupropion 150 mg/day compared to placebo. 6
Dosing and Administration
Start with bupropion SR 100-150 mg daily or XL 150 mg daily. 1
Titrate to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL), with a maximum dose of 450 mg per day. 1
Bupropion requires 2-4 weeks to achieve full therapeutic effect, unlike stimulants which work within days. 1, 2
Critical Safety Considerations
Common side effects include headache, insomnia, and anxiety—these can be mistaken for worsening ADHD symptoms and require close monitoring during the first 2-4 weeks. 1, 2
Never use MAO inhibitors concurrently with bupropion due to risk of hypertensive crisis and potential cerebrovascular accidents; allow at least 14 days between discontinuation of an MAOI and initiation of bupropion. 1, 2
Seizure risk increases at higher bupropion doses, particularly when combined with stimulants—use caution if considering combination therapy. 1, 2
Bupropion's activating properties can exacerbate hyperactivity, anxiety, or agitation, making it potentially problematic for patients with prominent hyperactivity or comorbid anxiety disorders. 1
Special Populations and Comorbidities
For patients with ADHD and substance abuse history, bupropion is a reasonable first-line alternative to stimulants since it is not a controlled substance and has lower abuse potential. 2, 4
For patients with ADHD and comorbid depression, consider starting with a stimulant first (which may indirectly improve mood by reducing ADHD-related functional impairment), then adding an SSRI if depressive symptoms persist—bupropion alone is not proven for dual treatment. 1, 2
For patients with ADHD and bipolar disorder, an open trial showed bupropion SR (up to 200 mg twice daily) reduced ADHD symptoms without significant activation of mania when used with adjunct mood stabilizers, though controlled trials are needed. 7
For pregnant patients, bupropion may be considered as an alternative to stimulants, though it carries a small increased risk of certain cardiovascular malformations with first-trimester exposure. 1, 2
Common Pitfalls to Avoid
Do not assume bupropion will adequately treat both ADHD and depression simultaneously—the evidence does not support this approach, and combination therapy is typically required. 1
Do not use bupropion as first-line when stimulants are appropriate—stimulants have significantly higher response rates (70-80% vs. more modest effects with bupropion) and faster onset of action. 1, 2
Monitor closely for worsening hyperactivity, insomnia, and anxiety during initial treatment, as bupropion's activating properties can worsen these symptoms rather than improve them. 1, 2
Be especially cautious in patients with comorbid anxiety disorders, as bupropion can exacerbate anxiety symptoms due to its activating mechanism of action. 1
Monitoring Requirements
Assess ADHD symptom response at 2-4 weeks and again at 6 weeks using standardized rating scales. 5, 6
Monitor for emergence or worsening of anxiety, insomnia, agitation, and headaches. 2, 4
Screen for suicidality, particularly when used in patients with comorbid depression. 3
Evaluate blood pressure and pulse, though cardiovascular effects are less pronounced than with stimulants. 3