Bupropion for ADHD Treatment

Position in Treatment Algorithm

The American Academy of Family Physicians suggests that bupropion should be considered as a second-line option when stimulants are contraindicated, not tolerated, or when there are concerns about stimulant misuse 1, 2
Stimulants remain the gold standard first-line treatment with 70-80% response rates and the strongest effect sizes for reducing core ADHD symptoms, supported by over 161 randomized controlled trials 1, 3

Bupropion is particularly useful in patients with a history of substance abuse where stimulants pose diversion risk 1
Bupropion is useful in patients who need weight loss, as it is the only antidepressant consistently shown to promote weight loss 1, 2
Bupropion can be used in patients requiring smoking cessation alongside ADHD treatment 4

The recommended starting dose is bupropion SR 100-150 mg daily or XL at 150 mg daily 5, 2
The dose can be titrated to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL) 5, 2
The maximum dose is 450 mg per day 5, 2
Bupropion requires 2-4 weeks to achieve full therapeutic effect, so set appropriate expectations with patients 1, 2

Bupropion is activating and can exacerbate anxiety, agitation, or hyperactivity 4, 1
Bupropion should not be used in patients with seizure disorders as it lowers seizure threshold 4
Monitor closely for worsening hyperactivity, insomnia, anxiety, and agitation during the first 2-4 weeks 1
Screen for suicidality, particularly when used in patients with comorbid depression 2
Never use MAO inhibitors concurrently with bupropion due to risk of hypertensive crisis—at least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion 1, 2
Give the second dose before 3 p.m. to minimize risk of insomnia 4

Common side effects include headache, insomnia, and anxiety, which are generally less severe than with stimulants 4, 1

If ADHD symptoms improve with bupropion but depressive symptoms persist after 4-6 weeks, add an SSRI to the regimen, as 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

The American College of Obstetricians and Gynecologists recommends starting with bupropion SR 100-150 mg daily or XL 150 mg daily, with titration to maintenance doses, for patients with ADHD, with a maximum dose of 450 mg per day 6, 7, 8, 9
The dosing regimen for bupropion SR formulation is 100-150 mg twice daily, and for XL formulation is 150-300 mg daily, for patients with ADHD 6, 7, 8, 9

The American College of Obstetricians and Gynecologists notes that bupropion does not appear to be associated with major congenital malformations overall, but small absolute increases in left ventricular outflow tract obstruction and ventricular septal defects have been reported with first-trimester exposure, in pregnant patients with ADHD 6, 7, 8, 9
Caution is advised during breastfeeding, as bupropion is present in human milk at very low levels, with generally no adverse events reported, but two case reports of seizures in breastfed infants exist, for patients with ADHD 6, 7, 8, 9