Non-Stimulant Medications for Adults with ADHD

Introduction to Non-Stimulant Medications

The American Academy of Child and Adolescent Psychiatry recommends atomoxetine as a first-line non-stimulant medication for adults with ADHD, with proven efficacy in multiple controlled trials 1
Atomoxetine demonstrates a 28-30% reduction in ADHD symptom scores versus 18-20% with placebo in controlled adult trials, although the full therapeutic effects require 6-12 weeks 2, 1
The medication provides continuous 24-hour symptom coverage without peaks and valleys 3, 1

The recommended dosing for atomoxetine is 40 mg/day for adults, then titrated to a target dose of 80-100 mg/day, with a maximum of 100 mg/day (or 1.4 mg/kg/day, whichever is lower) 1
Weight-based dosing for guanfacine is approximately 0.1 mg/kg once daily 2
Guanfacine is available in 1, 2, 3, and 4 mg tablets and should be administered in the evening due to sedation risk 2, 3

Non-controlled substance status eliminates abuse potential and allows easier prescription refills, particularly indicated for patients with comorbid substance use disorders where stimulants pose diversion risk 3, 4
Lower risk of exacerbating anxiety symptoms compared to stimulants 3
Fewer effects on appetite and growth with long-term use 3

FDA Black Box Warning: Monitor closely for suicidal ideation, especially during the first few weeks of treatment 1
Assess blood pressure and heart rate at baseline and with dose increases 1
Common adverse effects include somnolence, fatigue, irritability, insomnia, nightmares 2

Guanfacine extended-release should be considered when atomoxetine is ineffective or poorly tolerated, particularly in patients with comorbid anxiety, tics, or sleep disturbances 2, 3, 4
Bupropion may be considered as a third-line agent, particularly when comorbid depression is present, though it is not FDA-approved for ADHD 5, 6, 4
Viloxazine (Qelbree) is FDA-approved for adults with ADHD, offering another non-stimulant option, with a starting dose of 200 mg once daily and a maximum dose of 600 mg once daily 7

Start with atomoxetine unless specific contraindications exist (severe cardiovascular disease, narrow-angle glaucoma) 2, 1
Switch to guanfacine if atomoxetine is ineffective after 12 weeks at therapeutic dose, or if intolerable side effects from atomoxetine occur, or if comorbid tics, anxiety, or sleep disturbances are present 2, 1, 3, 4
Consider bupropion if both atomoxetine and guanfacine have failed, or if comorbid depression requires treatment 5, 6, 4

Baseline monitoring should include blood pressure, heart rate, weight, and suicidality assessment 1
Follow-up monitoring (2-4 weeks) should include vital signs, side effects, and early response 1
Therapeutic assessment (6-12 weeks for atomoxetine, 2-4 weeks for guanfacine) should include ADHD symptom scales, functional impairment, and quality of life 2, 1
Ongoing monitoring should include quarterly vital signs, annual growth parameters if applicable, and continuous suicidality monitoring 1

The American Academy of Child and Adolescent Psychiatry notes that atomoxetine has a delayed onset of action, substantially longer than stimulant medications, which work within 30 minutes to 2 hours after administration 8, 9