Efficacy of Bupropion for ADHD Treatment
Bupropion is a second-line treatment for ADHD with moderate efficacy, showing approximately 53% response rate compared to 31% for placebo, but is less effective than stimulant medications which remain first-line therapy. 1
Treatment Algorithm for ADHD
First-line Treatment Options
- Stimulant medications (methylphenidate and amphetamine-based stimulants) are the first-line pharmacologic treatments for ADHD due to their superior efficacy, working for 70-80% of patients 2
- Methylphenidate is recommended for children and adolescents, while amphetamines are preferred for adults 2
Second-line Treatment Options (When to Consider Bupropion)
- When stimulants are ineffective or cause intolerable side effects 2
- For patients with comorbid depression 3
- For patients with concerns about stimulant misuse or diversion 2
- For adolescents with substance use disorders 4
Evidence for Bupropion's Efficacy in ADHD
Adult ADHD
- In a randomized, placebo-controlled study of 162 adults with ADHD, bupropion XL showed a 53% response rate compared to 31% for placebo (p=0.004) 1
- Effect size for bupropion in adult ADHD is approximately 0.6, which is moderate but lower than stimulants 1
- Bupropion provides sustained benefit throughout the day (morning, afternoon, and evening) compared to placebo 1
Children and Adolescents
- Head-to-head trials found bupropion had comparable efficacy to methylphenidate in children and adolescents, though with smaller effect sizes 4
- In a double-blind crossover trial, bupropion (mean dose 3.3 mg/kg/day) and methylphenidate (mean dose 0.7 mg/kg/day) showed equivalent improvement on the Iowa-Conners Teacher's Rating Scale 5
- Bupropion may be particularly beneficial in children with comorbid ADHD and conduct, substance use, or depressive disorders 4
Dosing Considerations
- For sustained-release (SR) formulation: Starting dose 100-150 mg daily, maintenance dose 100-150 mg twice daily 2
- For extended-release (XL) formulation: Starting dose 150 mg daily, maintenance dose 150-300 mg daily, maximum dose 450 mg daily 2
- Titration should be gradual to minimize side effects 2
Safety Profile
- Generally well-tolerated with a low rate of drug-related study discontinuation (5%) 1
- Headaches may be less frequent with bupropion compared to methylphenidate 4
- No serious or unexpected adverse events reported in clinical trials 1
- Caution is advised during pregnancy due to limited data, though it does not appear to be associated with major congenital malformations 2
- Limited data on use during breastfeeding - bupropion is present in breast milk at low levels 2
Clinical Caveats and Considerations
- Bupropion works through inhibition of dopamine and norepinephrine reuptake, which is relevant to ADHD pathophysiology 3
- The medication may be particularly useful in patients with comorbid depression and ADHD 3
- Evidence base for bupropion in ADHD is more limited than for stimulants and atomoxetine 4
- Current guidelines do not list bupropion as a first-line agent for ADHD treatment 2
- When considering bupropion for ADHD, the extended-release formulation (XL) provides better all-day coverage 1