Drug Interactions and Precautions with Bupropion and Atomoxetine

Introduction to Combination Therapy

The American Academy of Child and Adolescent Psychiatry suggests that atomoxetine dosing should typically start at 40 mg daily with titration every 7-14 days to 60-80 mg/day, with maximum dosing at the lesser of 1.4 mg/kg/day or 100 mg/day 1, 2, 3
Bupropion dosing ranges from 100-150 mg daily (SR formulation BID) to 150-300 mg daily (XL formulation), with a maximum of 450 mg per day, as recommended by the American Academy of Child and Adolescent Psychiatry 1, 2, 3

Monitor for early signs of serotonin syndrome, including mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia), as advised by the Journal of the American Academy of Child and Adolescent Psychiatry 4
Symptoms of serotonin syndrome can arise within 24-48 hours after combining medications or dose changes, according to the Journal of the American Academy of Child and Adolescent Psychiatry 4

Start atomoxetine at a lower dose (consider 40 mg daily or less) if bupropion is already being taken, as recommended by the American Academy of Child and Adolescent Psychiatry 1, 2, 3
Watch for early signs of adverse effects, including agitation, tremor, insomnia, and autonomic symptoms in the first 24-48 hours after initiation or dose changes, as advised by the Journal of the American Academy of Child and Adolescent Psychiatry 4

The American Academy of Child and Adolescent Psychiatry notes that there are no published case reports of serious adverse events when combining bupropion with atomoxetine, and the principle of combining these agents extends to atomoxetine given its similar noradrenergic mechanism 5

The American Academy of Child and Adolescent Psychiatry recommends monitoring for cardiovascular effects, particularly in patients with pre-existing cardiac conditions, when combining atomoxetine and bupropion 5
Bupropion is absolutely contraindicated in patients with seizure disorders, history of stroke or brain metastases, and current MAO inhibitor use, and both medications require monitoring for neuropsychiatric effects and hepatic function 5

The American Academy of Child and Adolescent Psychiatry suggests scheduling follow-up at 2 weeks, then monthly, once stabilized on the combination of atomoxetine and bupropion 5