What are non-stimulant medication options for Attention Deficit Hyperactivity Disorder (ADHD) in adults?

Non-Stimulant Medication Options for ADHD in Adults

First-Line Non-Stimulant: Atomoxetine

Atomoxetine should be your first-line non-stimulant choice for adult ADHD, starting at 40 mg/day and titrating to a target dose of 80-100 mg/day over several weeks, with full therapeutic effect expected in 6-12 weeks. 1, 2

Dosing Protocol

• Start at 40 mg/day, then titrate to target dose of 80-100 mg/day 1, 2
• Maximum dose is 100 mg/day or 1.4 mg/kg/day, whichever is lower 1, 3
• Can be administered once daily or split into two doses to reduce adverse effects 1
• Full therapeutic effect requires 6-12 weeks, substantially longer than stimulants which work within 30 minutes to 2 hours 1, 2

Efficacy Data

• Achieves 28-30% reduction in ADHD symptom scores versus 18-20% with placebo 1, 2, 4
• Effect size of approximately 0.7 compared to placebo 1
• Provides continuous 24-hour symptom coverage without peaks and valleys 1, 2

Key Advantages

• Non-controlled substance status eliminates abuse potential and allows easier prescription refills 2
• Lower risk of exacerbating anxiety symptoms compared to stimulants 1, 2
• Particularly beneficial for patients with comorbid substance use disorders, comorbid anxiety or autism spectrum disorder, and tic disorders 1, 2
• Fewer effects on appetite and growth with long-term use compared to stimulants 1, 2

Critical Safety Monitoring

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

Common Adverse Effects

• Most common in adults: dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems, and palpitations 4, 5
• Fewer and less pronounced adverse effects compared to guanfacine and clonidine 1
• Discontinuation rate of 7.8-9.3% versus 2.4-4.3% for placebo 4

---

Second-Line Non-Stimulant: Guanfacine Extended-Release

If atomoxetine is ineffective after 12 weeks at therapeutic dose or causes intolerable side effects, switch to guanfacine extended-release at approximately 0.1 mg/kg once daily (typical range 1-7 mg/day). 1, 2

Dosing Protocol

• Weight-based dosing: approximately 0.1 mg/kg once daily 1, 2
• Typical range: 1-7 mg/day 1
• Available in 1,2,3, and 4 mg tablets 2
• Administer in the evening due to sedation risk 1, 2
• Requires 2-4 weeks before clinical benefits are observed 1, 2

Efficacy Data

• Effect size of approximately 0.7 compared to placebo 1

Specific Indications

• Particularly indicated for patients with comorbid tic disorders, anxiety disorders, or sleep disturbances due to sedating properties 1, 2
• FDA-approved as adjunctive therapy to stimulants to increase treatment effects and/or decrease stimulant adverse effects, particularly sleep disturbances and cardiovascular effects 1

Critical Safety Warning

• FDA warning against abrupt discontinuation: Must be tapered by 1 mg every 3-7 days to avoid rebound hypertension 1, 2
• Frequent adverse effect of somnolence/sedation 1

---

Third-Line Option: Viloxazine (Qelbree)

Viloxazine is FDA-approved for adults with ADHD and offers another non-stimulant option when both atomoxetine and guanfacine have failed. 2, 6

Dosing Protocol

• Starting dose: 200 mg once daily 2
• Maximum dose: 600 mg once daily 2
• Classified as a serotonin norepinephrine modulating agent 6

---

Fourth-Line Option: Bupropion

Consider bupropion as a third-line agent, particularly when comorbid depression is present, though it is not FDA-approved for ADHD. 2, 6

Key Considerations

• Should only be considered if both atomoxetine and guanfacine have failed 2
• Particularly useful when comorbid depression requires treatment 2
• Not FDA-approved for ADHD 2
• Common side effects include headache, insomnia, and anxiety 7

---

Treatment Algorithm for Non-Stimulant Selection

1. Start with atomoxetine unless specific contraindications exist (severe cardiovascular disease, narrow-angle glaucoma) 2

2. Switch to guanfacine if:

   • Atomoxetine is ineffective after 12 weeks at therapeutic dose 2
   • Intolerable side effects from atomoxetine occur 2
   • Comorbid tics, anxiety, or sleep disturbances are present 2

3. Consider viloxazine if both atomoxetine and guanfacine have failed 2

4. Consider bupropion if:

   • Both atomoxetine and guanfacine have failed 2
   • Comorbid depression requires treatment 2

---

Ongoing Monitoring Parameters

• Quarterly vital signs (blood pressure and heart rate) 1, 2
• Annual growth parameters if applicable 1, 2
• Continuous suicidality monitoring, especially with atomoxetine 1, 2
• ADHD symptom scales, functional impairment, and quality of life assessments 1, 2

---

Common Pitfalls to Avoid

• Do not expect rapid response with atomoxetine: Full therapeutic effects require 6-12 weeks, unlike stimulants which work within hours 1, 2
• Do not abruptly discontinue guanfacine: Must taper by 1 mg every 3-7 days to avoid rebound hypertension 1, 2
• Do not prescribe atomoxetine first-line when fatigue is a chief complaint: Somnolence and fatigue are common adverse effects that would worsen the patient's symptoms 1
• Do not assume a single antidepressant will effectively treat both ADHD and depression: No single antidepressant is proven for this dual purpose 7