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

Bupropion for ADHD: A Second-Line Alternative

Bupropion can be used to treat ADHD in adults, but it should be considered a second-line option after stimulants have been tried, are contraindicated, or when specific clinical circumstances make it preferable. 1, 2

Position in Treatment Algorithm

Stimulants remain the gold standard first-line treatment for ADHD, with 70-80% response rates and the largest effect sizes supported by over 161 randomized controlled trials. 1, 2 Bupropion should be considered only after stimulants (methylphenidate, dextroamphetamine, or mixed amphetamine salts) have failed, caused intolerable side effects, or are contraindicated. 1, 2

The evidence shows that bupropion has smaller effect sizes compared to stimulants, though it does demonstrate efficacy. 3 A 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. 3

Specific Clinical Scenarios Where Bupropion Is Preferred

Bupropion is particularly useful in the following situations:

• Active substance abuse disorder or history of stimulant misuse/diversion - Bupropion has no abuse potential and avoids the controlled substance concerns of stimulants. 1, 2
• Comorbid depression requiring treatment - Though no single antidepressant effectively treats both ADHD and depression as monotherapy, bupropion addresses both conditions simultaneously. 1, 2
• Need for weight loss - Bupropion is the only antidepressant consistently shown to promote weight loss. 1, 2
• Smoking cessation alongside ADHD treatment - Bupropion is FDA-approved for smoking cessation. 2
• Comorbid bipolar disorder - Open trial data suggests bupropion may treat ADHD in bipolar patients without activating mania when used with mood stabilizers. 4

Dosing and Administration

Start with bupropion SR 100-150 mg daily or XL 150 mg daily. 5, 2

Titrate to maintenance doses:

• SR formulation: 100-150 mg twice daily 5, 2
• XL formulation: 150-300 mg daily 5, 2
• Maximum dose: 450 mg per day 5, 2

Give the second SR dose before 3 p.m. to minimize insomnia risk. 2 Bupropion requires 2-4 weeks to achieve full therapeutic effect, unlike stimulants which work within days. 1, 2

Critical Safety Considerations and Contraindications

Absolute contraindications:

• Seizure disorders - Bupropion lowers seizure threshold. 2
• Current or recent MAO inhibitor use - At least 14 days must elapse between discontinuing an MAOI and starting bupropion due to hypertensive crisis risk. 1, 2

Use with extreme caution in:

• Patients with prominent hyperactivity or anxiety - Bupropion is inherently activating and can exacerbate these symptoms. 1, 2
• Eating disorders - Increased seizure risk. 2

Monitor closely during the first 2-4 weeks for:

• Worsening hyperactivity, insomnia, anxiety, and agitation 1, 2
• Suicidality, particularly in patients with comorbid depression 2
• Blood pressure and pulse (though cardiovascular effects are less pronounced than with stimulants) 1

Common side effects include headache, insomnia, and anxiety, which are generally less severe than with stimulants. 1, 2

When Combination Therapy Is Needed

If ADHD symptoms improve with bupropion but depressive symptoms persist after 4-6 weeks, add an SSRI to the regimen. 1, 2 There are no significant drug-drug interactions between bupropion and SSRIs. 1, 2

No single antidepressant, including bupropion, is proven to effectively treat both ADHD and depression as monotherapy - combination therapy is often required. 1, 2

Alternatively, if bupropion provides inadequate ADHD symptom control, adding a stimulant to bupropion may enhance efficacy, particularly when comorbid depressive symptoms are present. 1 There are no specific warnings against combining bupropion with stimulants, though careful monitoring for side effects is necessary. 1

Special Population: Pregnancy and Breastfeeding

Bupropion does not appear to be associated with major congenital malformations overall, though small absolute increases in left ventricular outflow tract obstruction and ventricular septal defects have been reported with first-trimester exposure. 5 Confounding by indication cannot be ruled out, and other studies have not consistently found these associations. 5

Caution is advised during breastfeeding - Bupropion is present in human milk at very low levels, with generally no adverse events reported, though two case reports of seizures in breastfed infants exist. 5

Common Pitfalls to Avoid

• Do not assume bupropion will adequately treat both ADHD and depression as monotherapy - Evidence does not support this approach. 1, 2
• Do not use bupropion as first-line when stimulants have not been tried - Stimulants have superior efficacy and should be attempted first unless contraindicated. 1, 2
• Do not prescribe bupropion to patients with prominent hyperactivity without warning them about potential worsening - The activating properties can exacerbate hyperactive symptoms. 1, 2
• Do not expect immediate results - Set appropriate expectations that 2-4 weeks are needed for full therapeutic effect. 1, 2