What are the effects of Wellbutrin (bupropion) on Attention Deficit Hyperactivity Disorder (ADHD) symptoms?

Wellbutrin (Bupropion) for ADHD: Effects on Symptoms

Bupropion is a second-line medication for ADHD that can reduce symptom severity, but stimulants (methylphenidate or amphetamines) remain the gold standard first-line treatment with superior efficacy. 1, 2

Evidence for Efficacy

Bupropion demonstrates moderate effectiveness for ADHD symptoms, though with smaller effect sizes compared to stimulants:

• 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). 3

• In a randomized controlled trial of 42 adults with ADHD, bupropion 150 mg/day showed significant improvement over placebo after 6 weeks on the Conners' Adult ADHD Rating Scales. 4

• A systematic review of pediatric studies found that bupropion demonstrated efficacy comparable to methylphenidate in head-to-head trials, though a large multicenter study showed smaller effect sizes for bupropion based on teacher and parent ratings. 5

• Stimulants achieve a 70-80% response rate for ADHD treatment, substantially higher than bupropion's response rates. 1, 2

Clinical Positioning in Treatment Algorithm

Bupropion should be considered as a second-line option when stimulants are contraindicated, not tolerated, or when patients have concerns about stimulant misuse or diversion. 1, 2

Specific scenarios where bupropion may be preferred include:

• Patients with comorbid substance use disorders, where atomoxetine or bupropion are preferred over stimulants due to lower abuse potential. 1
• Patients with comorbid depression requiring treatment for both conditions, though no single antidepressant is proven to effectively treat both ADHD and depression simultaneously. 1
• Patients who cannot tolerate stimulant side effects such as appetite suppression or sleep disturbances. 2
• Patients with comorbid smoking cessation needs or weight concerns from other medications. 1

Dosing Recommendations

For sustained-release (SR) formulation: start at 100-150 mg daily, titrate to maintenance dose of 100-150 mg twice daily. 2

For extended-release (XL) formulation: start at 150 mg daily, titrate to maintenance dose of 150-300 mg daily, with a maximum of 450 mg daily. 2

• Titration should be gradual to minimize side effects. 2
• Clinical studies have used dosages ranging from 150 mg to 450 mg daily over 6-10 week treatment periods. 3

Safety and Tolerability

Bupropion's tolerability profile is similar to placebo, with no significant difference in withdrawal rates due to adverse effects (risk ratio 1.20). 3

Common side effects to monitor include:

• Headache, insomnia, and anxiety (bupropion's activating properties). 1
• Seizure risk, particularly at higher doses or when combined with stimulants. 1
• Worsening of hyperactivity or agitation in patients with prominent hyperactive symptoms. 1

Bupropion is contraindicated with MAO inhibitors due to risk of hypertensive crisis; at least 14 days must elapse between discontinuation of an MAOI and initiation of bupropion. 1

Important Clinical Caveats

Bupropion may be inappropriate for patients with prominent hyperactivity or comorbid anxiety disorders, as its activating properties can exacerbate these symptoms. 1

• Monitor closely for worsening hyperactivity, insomnia, anxiety, and agitation during the first 2-4 weeks of treatment. 1
• Be especially cautious in patients with seizure disorders, as bupropion lowers the seizure threshold. 1
• When used for comorbid depression and ADHD, screen for suicidality, particularly during early treatment phases. 1

Combination Therapy Considerations

If ADHD symptoms improve on stimulants but depressive symptoms persist, adding an SSRI to the stimulant regimen is preferred over switching to bupropion alone. 1

• Bupropion can be added to stimulant medication to enhance ADHD symptom control when stimulants alone are insufficient, though careful monitoring for side effects is necessary. 1
• There are no significant pharmacokinetic interactions between bupropion and stimulants, but the combination may increase seizure risk. 1

Special Populations

In patients with substance use history, long-acting stimulant formulations or atomoxetine are generally preferred over bupropion as first-line treatment. 1

• An open trial in adults with ADHD and active substance use disorders found that bupropion-SR produced clinically significant reductions in ADHD symptoms (-43% on ADHD Rating Scale) but negligible effects on substance use. 6

During pregnancy, bupropion has been associated with a small increased risk of left ventricular outflow tract obstruction and ventricular septal defects with first-trimester exposure (adjusted odds ratio 2.9). 7