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

Non-Stimulant Medication Options for Adult ADHD

Atomoxetine is the primary FDA-approved non-stimulant medication for adult ADHD, with a recommended starting dose of 0.5 mg/kg/day and target dose of 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg/day). 1

First-Line Non-Stimulant Option

Atomoxetine (Strattera)

• Mechanism: Selectively inhibits norepinephrine transporters, enhancing noradrenergic transmission in the prefrontal cortex 1
• Dosing:
  • Starting dose: 0.5 mg/kg/day
  • Target dose: 1.2 mg/kg/day
  • Maximum dose: 1.4 mg/kg/day or 100 mg/day (whichever is lower)
  • Dose adjustments typically every 7-14 days 1
  • Can be administered once daily in the morning or as divided doses 2
• Efficacy: Moderate effectiveness with an effect size of ~0.7 (compared to ~1.0 for stimulants) 1
• Clinical evidence: Demonstrated significant improvement in ADHD symptoms compared to placebo in multiple clinical trials, with mean reductions in ADHD symptom scores of approximately 28-30% (vs. 18-20% for placebo) 3

Other Non-Stimulant Options

Antidepressants with Noradrenergic/Dopaminergic Effects

• Bupropion: Has shown demonstrable efficacy in adult ADHD 3
• Tricyclic antidepressants: Effective but limited by side effects 4
• Viloxazine: Recently studied with positive results for adult ADHD 3

Alpha-2 Adrenergic Agonists

• Guanfacine (extended-release): Evidence supports efficacy in adult ADHD 3
• Clonidine (extended-release): Less studied in adults but mentioned in guidelines 1

Clinical Considerations for Medication Selection

When to Consider Non-Stimulants

1. Patients who don't respond to stimulants (10-30% of ADHD patients) 4
2. Patients who cannot tolerate stimulant side effects 4
3. Patients with substance use concerns (non-stimulants have lower abuse potential) 1
4. Patients who prefer not to take a controlled substance 5

Monitoring Requirements

• Regular assessment of vital signs (blood pressure, heart rate) due to potential cardiovascular effects 1
• Monitoring for side effects:
  • Most common in adults: dry mouth, insomnia, nausea, decreased appetite, constipation, urinary issues, sexual dysfunction, dizziness 5
  • Withdrawal rates due to adverse events: approximately 7.8-9.3% (vs. 2.4-4.3% for placebo) 5
• Regular follow-up within 2-4 weeks after medication changes 1
• Screening for suicidal ideation, particularly when initiating therapy in young adults 1

Practical Approach to Non-Stimulant Treatment

1. Initial Assessment:

   • Confirm ADHD diagnosis
   • Screen for comorbidities (emotional/behavioral, developmental, physical conditions)
   • Assess for substance use concerns or contraindications to stimulants

2. Medication Selection Algorithm:

   • If stimulants are contraindicated, not tolerated, or ineffective → Atomoxetine as first non-stimulant choice
   • If atomoxetine is ineffective or not tolerated → Consider alpha-2 agonists or antidepressants based on comorbidities

3. Dosing Strategy for Atomoxetine:

   • Begin with 0.5 mg/kg/day
   • Titrate gradually every 1-2 weeks
   • Target 1.2 mg/kg/day for optimal effect
   • May administer once daily or in divided doses

4. Monitoring Schedule:

   • Follow-up within 2-4 weeks after initiation or dose changes
   • Regular assessment of vital signs and side effects
   • Evaluate treatment response using standardized measures

Important Caveats

• Non-stimulants generally have a slower onset of action compared to stimulants
• Atomoxetine may take 2-4 weeks to show full therapeutic effect
• When combining with other medications (especially SSRIs), monitor closely for drug interactions and serotonin syndrome 1
• Consider augmenting pharmacotherapy with Cognitive Behavioral Therapy (CBT), which is particularly effective when combined with medication 1