Wellbutrin (Bupropion) Dosing for ADHD
Bupropion is not FDA-approved for ADHD treatment, but when used off-label, start with sustained-release (SR) formulation at 100-150 mg daily, titrate to a maintenance dose of 100-150 mg twice daily, or use extended-release (XL) formulation starting at 150 mg daily with maintenance dosing of 150-300 mg daily, not exceeding a maximum of 450 mg per day. 1
Important Context: Off-Label Use
Bupropion is not a first-line treatment for ADHD. Stimulants (methylphenidate, lisdexamfetamine) should be used as first-line therapy, with non-stimulants like atomoxetine, guanfacine, or clonidine as second-line options before considering bupropion. 1 Bupropion is typically reserved for situations where stimulants are contraindicated, not tolerated, or when there are specific comorbidities like depression or smoking cessation needs. 2
Specific Dosing Regimens
Sustained-Release (SR) Formulation
- Starting dose: 100-150 mg orally once daily 1
- Maintenance dose: 100-150 mg orally twice daily (BID) 1
- Timing: Administer at 7 AM and 7 PM to provide coverage throughout the day 3
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 (applies to both formulations) 1
- Titration: In clinical trials, doses up to 450 mg/day were used with good tolerability 4
Evidence for Efficacy
Low-quality evidence suggests bupropion decreases ADHD symptom severity with a standardized mean difference of -0.50 and increases clinical improvement rates (RR 1.50). 2 The effect size is approximately 0.6, which is smaller than standard stimulant medications but clinically meaningful. 4
- Onset of action: Significant improvement can be seen as early as week 2-3 of treatment 5, 4
- Response rate: Approximately 53% of patients respond (defined as ≥30% reduction in ADHD symptoms) compared to 31% with placebo 4
- Duration of effect: XL formulation provides sustained benefit throughout morning, afternoon, and evening 4
Clinical Considerations
When to Consider Bupropion
- Comorbid depression: Bupropion is FDA-approved for depression and can address both conditions 2
- Comorbid bipolar disorder: May be safer than stimulants in patients with bipolar II disorder, though caution is still warranted 6
- Smoking cessation needs: Dual benefit for ADHD and nicotine dependence 2
- Stimulant non-responders or intolerance: Alternative when first-line agents fail 2
Safety Monitoring
- Seizure risk: This is the most critical concern—bupropion lowers seizure threshold, particularly at doses >450 mg/day 2
- Dermatological reactions: Monitor for rash and urticaria, which may require discontinuation 3
- Tolerability: Low-quality evidence suggests similar withdrawal rates to placebo (RR 1.20), indicating generally good tolerability 2
Common Pitfalls
- Exceeding maximum dose: Never exceed 450 mg/day due to dose-dependent seizure risk 1
- Expecting immediate results: Unlike stimulants, bupropion requires 2-6 weeks for full therapeutic effect 2, 5
- Using as first-line in children: Evidence is primarily in adults; pediatric use requires careful consideration and is less well-established 3
Special Populations
Pregnancy and Breastfeeding
- Pregnancy: Bupropion does not appear to increase major congenital malformations, though some studies suggest possible small increases in specific cardiac defects (left ventricular outflow tract obstruction, ventricular septal defects) 1
- Breastfeeding: Caution advised—bupropion is present in breast milk with two case reports of seizures in breastfed infants 1