What is the typical dosing of Wellbutrin (bupropion) for Attention Deficit Hyperactivity Disorder (ADHD)?

Wellbutrin (Bupropion) Dosing for ADHD

For ADHD in adults, start bupropion sustained-release (SR) at 100-150 mg once daily, then titrate to a maintenance dose of 100-150 mg twice daily; for extended-release (XL), start at 150 mg daily and increase to a maintenance dose of 150-300 mg daily, with a maximum of 450 mg per day. 1

Dosing Algorithm

Sustained-Release (SR) Formulation

• Starting dose: 100-150 mg orally once daily 1
• Maintenance dose: 100-150 mg orally twice daily 1
• Titration approach: Increase weekly by 100 mg increments based on response and tolerability 2

Extended-Release (XL) Formulation

• Starting dose: 150 mg orally once daily 1
• Maintenance dose: 150-300 mg orally once daily 1
• Maximum dose: 450 mg per day (across all formulations) 1

Clinical Context and Evidence Quality

Bupropion is considered a second-line, off-label treatment for ADHD when stimulants (methylphenidate, amphetamines) are not tolerated, contraindicated, or ineffective. 1 The evidence base shows moderate efficacy with low-quality evidence overall. 3

Efficacy Data

• Symptom reduction: Bupropion decreases ADHD symptom severity with a standardized mean difference of -0.50 (95% CI -0.86 to -0.15), representing approximately a 43% reduction in ADHD Rating Scale scores 3, 2
• Clinical improvement: 50% increased likelihood of achieving clinical improvement compared to placebo (RR 1.50,95% CI 1.13 to 1.99) 3
• Time to effect: Clinical benefits typically emerge within 3-6 weeks of treatment 3, 2, 4

Special Populations

ADHD with Comorbid Substance Use Disorders

• Use the same dosing schedule: start at 100 mg SR, titrate weekly to target of 200 mg twice daily 2
• Important caveat: Bupropion effectively treats ADHD symptoms but shows minimal impact on active substance use itself 2
• This population may particularly benefit since stimulants carry abuse potential 2, 5

ADHD with Comorbid Bipolar Disorder

• Same dosing applies: up to 200 mg SR twice daily 6
• Requires concurrent mood stabilizers or antipsychotics for bipolar management 6
• Monitor closely for mood destabilization, though bupropion appears less likely to trigger mania than other antidepressants 6

Safety Considerations

Seizure Risk

Critical warning: Bupropion lowers seizure threshold. Absolute contraindication in patients with seizure disorders or conditions that increase seizure risk. 1 This is the primary safety concern limiting its use.

Tolerability

• Withdrawal rates due to adverse effects are similar to placebo (RR 1.20,95% CI 0.35 to 4.10) 3
• Common side effects include insomnia (give second dose before 3 PM), decreased appetite, and activation 1
• Avoid in agitated patients due to activating properties 1

Practical Implementation

When to Consider Bupropion

1. After stimulant failure: Try all three stimulant classes (methylphenidate, dextroamphetamine, mixed amphetamine salts) before switching to bupropion 1
2. Active substance use disorder: Bupropion is preferred over stimulants in this population 1, 2
3. Comorbid depression: Dual benefit for both conditions 1
4. Smoking cessation needed: Additional therapeutic benefit 3

Monitoring Parameters

• Baseline assessment: Screen for seizure history, eating disorders, abrupt alcohol/benzodiazepine discontinuation 1
• Ongoing monitoring: ADHD symptom scales (CAARS or ADHD-RS) at weeks 3 and 6 4
• Clinical Global Impression scales to track overall improvement 2, 4

Duration of Trial

Allow 6 weeks at therapeutic dose before declaring treatment failure, as onset of benefit may be gradual compared to stimulants' rapid effect. 3, 4

Evidence Limitations

The evidence quality is rated as low due to small sample sizes (total 438 participants across 6 studies) and methodological concerns including industry funding in most trials. 3 However, the consistency of findings across multiple studies supports clinical utility as a second-line agent. 3, 4