What is the recommended approach for using Strattera (Atomoxetine) versus Guanfacine to treat ADHD symptoms, including hyperactivity and restlessness?

Strattera vs. Guanfacine for ADHD Treatment

For ADHD treatment, atomoxetine (Strattera) should be used as first-line non-stimulant therapy for core ADHD symptoms, while guanfacine is better suited as an adjunctive therapy or for patients with predominant hyperactivity and restlessness symptoms. 1, 2

Medication Mechanisms and Indications

Atomoxetine (Strattera)

• Selective norepinephrine reuptake inhibitor that increases both norepinephrine and dopamine in the prefrontal cortex 3, 4
• FDA-approved for ADHD treatment in children (6+ years), adolescents, and adults
• Starting dose: 0.5 mg/kg/day
• Target dose: 1.2 mg/kg/day 2
• Can be administered once daily or in divided doses 4
• Particularly useful for patients with:
  • Substance use concerns (no abuse potential) 2, 4
  • Comorbid anxiety 4
  • Tics 4

Guanfacine (Intuniv)

• Alpha-2A adrenergic receptor agonist 5, 6
• FDA-approved for ADHD in children and adolescents
• Starting dose: 1 mg daily 2
• Primarily effective for hyperactivity and impulsivity symptoms 5
• FDA-approved as adjunctive therapy with stimulants 1

Efficacy Comparison

Atomoxetine

• Effect size of approximately 0.7 (vs. 1.0 for stimulants) 2
• Demonstrated efficacy in multiple controlled trials 4
• Effective for both inattentive and hyperactive/impulsive symptoms 3
• Efficacy extends into evening hours with morning dosing 4

Guanfacine

• Efficacy rate of 58.5% vs. 29.4% for placebo in short-term studies (<10 weeks) 5
• Particularly effective for hyperactivity symptoms 5, 6
• Better evidence for efficacy in children than adults 5

Side Effect Profiles

Atomoxetine

• Common side effects: appetite loss, abdominal pain, headaches, somnolence, nausea 1, 4
• Cardiovascular: mild increases in heart rate and blood pressure 1, 4
• Growth: potential initial growth velocity decrease (1-2 cm from predicted adult height) 1
• Black box warning for suicidal ideation (rare but significant) 3, 4
• Rare liver injury (monitor for signs of liver problems) 3

Guanfacine

• Common side effects: somnolence (38.6%), headaches (20.5%), fatigue (15.2%) 5
• Cardiovascular: decreased heart rate and blood pressure 1
• Risk of rebound hypertension with abrupt discontinuation (requires tapering) 1
• Dizziness, dry mouth, irritability 1

Treatment Algorithm

1. Initial Assessment:

   • Determine predominant ADHD symptoms (inattention vs. hyperactivity/impulsivity)
   • Screen for comorbidities (anxiety, tics, substance use concerns)
   • Check baseline vital signs, height, weight

2. First-line Non-stimulant Treatment:

   • For comprehensive ADHD symptom treatment: Atomoxetine
     • Start at 0.5 mg/kg/day
     • Titrate to target dose of 1.2 mg/kg/day
     • Can be given once daily or divided into two doses

3. For Predominant Hyperactivity/Impulsivity:

   • Consider guanfacine as monotherapy
     • Start at 1 mg daily
     • Titrate based on response and tolerability

4. Inadequate Response to Initial Treatment:

   • If partial response to atomoxetine: Consider adding guanfacine as adjunctive therapy 1, 2
   • If inadequate response to guanfacine: Consider switching to atomoxetine

5. Monitoring:

   • Atomoxetine: Monitor for suicidal ideation, liver function, vital signs, growth
   • Guanfacine: Monitor blood pressure, heart rate, sedation levels

Special Considerations

• Substance use concerns: Atomoxetine preferred (no abuse potential) 2
• Cardiovascular issues:
  • With hypertension: Guanfacine may be beneficial due to BP-lowering effects
  • With hypotension: Atomoxetine may be preferred 1
• Sleep issues: Guanfacine may cause more sedation; atomoxetine less likely to exacerbate sleep problems 4
• Comorbid anxiety: Atomoxetine may be more beneficial 4

Important Caveats

• Never abruptly discontinue guanfacine due to risk of rebound hypertension 1
• Atomoxetine may take 4-6 weeks to reach full efficacy (unlike stimulants which work more quickly) 4
• Consider ECG before starting either medication in patients with cardiac risk factors 1
• Both medications require regular monitoring of vital signs and growth parameters 1, 2
• When combining medications, monitor closely for additive side effects 2