What non-stimulant, non-sedative medication options are available for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Non-Stimulant, Non-Sedative ADHD Medications

Atomoxetine is the first-line non-stimulant medication for ADHD when you need to avoid sedation, with FDA approval for both children and adults, providing 24-hour symptom coverage without abuse potential. 1, 2, 3

Primary Recommendation: Atomoxetine (Strattera)

Atomoxetine is your best option because it is the only non-stimulant that is definitively non-sedating and has the strongest evidence base. 1, 2

Dosing Protocol

• Adults: Start at 40 mg/day, then titrate to target dose of 80-100 mg/day (maximum 100 mg/day or 1.4 mg/kg/day, whichever is lower). 1, 2, 3
• Children/Adolescents: Target dose is 1.2 mg/kg/day, administered once or twice daily. 4
• Can be given as single morning dose or split into two doses to reduce adverse effects. 2

Expected Timeline

• Initial response: 2-4 weeks for early benefits. 1
• Full therapeutic effect: Requires 6-12 weeks at target dose. 1, 2
• Achieves 28-30% reduction in ADHD symptom scores versus 18-20% with placebo (effect size ~0.7). 1, 2

Key Advantages

• Non-sedating profile - does not cause somnolence like alpha-2 agonists. 2
• Provides continuous 24-hour symptom coverage without peaks and valleys. 1, 2
• Non-controlled substance with no abuse potential - easier prescription refills. 2, 5
• Lower risk of exacerbating anxiety compared to stimulants. 1, 2
• Less impact on appetite and growth versus stimulants. 2

Critical Safety Monitoring

• FDA Black Box Warning: Monitor closely for suicidal ideation, especially during first few weeks and dose adjustments. 1, 2
• Baseline assessment: blood pressure, heart rate, weight, suicidality screening. 1, 2
• Follow-up at 2-4 weeks: vital signs, side effects, early response. 1
• Therapeutic assessment at 6-12 weeks: ADHD symptom scales, functional impairment, quality of life. 1

Common Adverse Effects (Non-Sedating)

• Children/Adolescents: Dyspepsia, nausea, vomiting, decreased appetite, weight loss. 6
• Adults: Dry mouth, insomnia, nausea, decreased appetite, constipation, urinary retention, erectile dysfunction (~2%), dysmenorrhea, dizziness, decreased libido. 6, 5
• Discontinuation rate: 3.5% with atomoxetine versus 1.4% with placebo, dose-dependent (higher at >1.5 mg/kg/day). 6

Specific Indications Where Atomoxetine Excels

• Comorbid substance use disorders (no diversion risk). 2
• Comorbid anxiety or autism spectrum disorder. 2
• Tic disorders or Tourette's syndrome (does not worsen tics). 2
• Patients requiring continuous 24-hour coverage. 1, 2

Why NOT Guanfacine Extended-Release

Guanfacine is NOT appropriate for your request because it is inherently sedating, which directly contradicts your requirement for a non-sedative medication. 7, 1, 2

Sedation Profile of Guanfacine

• Somnolence/sedation is the most frequent adverse effect of guanfacine extended-release. 7, 1, 2
• Evening administration is preferable specifically due to sedating properties. 1, 2
• Also causes dizziness, dry mouth, bradycardia, hypotension, and abdominal pain. 7

When Guanfacine Would Be Considered (Despite Sedation)

• Second-line option only when atomoxetine fails after 12 weeks at therapeutic dose or causes intolerable side effects. 2
• Specifically indicated for comorbid tic disorders, anxiety disorders, or sleep disturbances where sedation is actually desired. 1, 2
• Dosing: ~0.1 mg/kg once daily, typical range 1-7 mg/day. 1, 2
• Must be tapered by 1 mg every 3-7 days upon discontinuation to avoid rebound hypertension. 7, 1, 2

Alternative Third-Line Options (Off-Label)

Viloxazine (Qelbree)

• FDA-approved non-stimulant for adults with ADHD. 2
• Starting dose: 200 mg once daily, maximum 600 mg once daily. 2
• Another non-sedating option if atomoxetine fails or is not tolerated. 2

Bupropion (Off-Label)

• Consider as third-line agent, particularly when comorbid depression is present. 2
• Not FDA-approved for ADHD but may be useful in specific circumstances. 2

Clinical Algorithm

1. Start with atomoxetine unless contraindications exist (severe cardiovascular disease, narrow-angle glaucoma). 2
2. Titrate to therapeutic dose (80-100 mg/day in adults) over 2-4 weeks. 1, 2
3. Assess response at 6-12 weeks - full therapeutic effect requires this duration. 1, 2
4. If inadequate response after 12 weeks at therapeutic dose: Consider viloxazine or bupropion (not guanfacine, due to sedation). 2
5. If intolerable side effects from atomoxetine: Switch to viloxazine or consider bupropion if comorbid depression. 2

Common Pitfalls to Avoid

• Do not discontinue atomoxetine prematurely - requires 6-12 weeks for full effect, unlike stimulants which work within 30 minutes to 2 hours. 2
• Do not use guanfacine if sedation is unacceptable - it is inherently sedating and contradicts the non-sedative requirement. 7, 1, 2
• Do not forget suicidality monitoring - FDA Black Box Warning requires close monitoring, especially early in treatment. 1, 2
• Do not abruptly discontinue guanfacine if it was ever used - must taper to avoid rebound hypertension. 7, 1, 2