Strattera (Atomoxetine) for ADHD: Dosing and Treatment Protocol
Position in Treatment Algorithm
Atomoxetine is FDA-approved as a second-line medication for ADHD, positioned after stimulants due to its smaller effect size (0.7 vs 1.0 for stimulants) and delayed onset of action requiring 6-12 weeks for full therapeutic effect. 1, 2
However, atomoxetine should be considered first-line in specific clinical scenarios:
- Patients with comorbid substance use disorders or at risk for substance abuse 1, 2
- Patients with comorbid tic disorders or Tourette's syndrome 2
- Adolescents at high risk for medication diversion 1
- Patients who prefer a non-controlled substance 3, 4
- Patients with sleep disturbances on stimulants 2
Dosing Protocol
Children and Adolescents (≤70 kg)
Start atomoxetine at 0.5 mg/kg/day, titrate after minimum 3 days to target dose of 1.2 mg/kg/day, with maximum dose of 1.4 mg/kg/day. 2, 5, 6
Children and Adolescents (>70 kg) and Adults
Start at 40 mg/day, titrate to target dose of 80 mg/day, with maximum dose of 100 mg/day. 2, 6
Administration Options
- Can be given as single daily dose (morning or evening) 2, 6
- Can be split into two evenly divided doses to reduce side effects 2, 3
- Provides 24-hour "around-the-clock" symptom coverage 2, 7
Dose Adjustments Required
Reduce dose by 50% in patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine), known CYP2D6 poor metabolizers, or those with moderate hepatic impairment. 6, 3
Age-Specific Considerations
Preschool Children (<6 years)
Atomoxetine is NOT recommended for preschool-aged children as it has not been adequately studied in this population. 1, 5
Elementary School-Aged Children (6-11 years)
Prescribe FDA-approved stimulant medications as first-line, with atomoxetine as second-line option when stimulants are contraindicated or ineffective. 1
Adolescents (12-18 years)
Prescribe FDA-approved medications with adolescent's assent; consider atomoxetine when substance abuse risk is present or medication diversion is a concern. 1
Critical Safety Monitoring
Black Box Warning: Suicidal Ideation
The FDA requires close monitoring for suicidal ideation, clinical worsening, and unusual behavior changes, especially during the first few months of treatment or with dose changes. 8, 2, 5, 6
This warning is based on meta-analysis showing increased risk of suicidal ideation in children and adolescents, though no completed suicides occurred in clinical trials. 6, 3
Hepatotoxicity
Discontinue atomoxetine immediately and do not restart if jaundice or laboratory evidence of liver injury develops. 8, 6
Rare cases of severe liver injury have been reported postmarketing. 3
Cardiovascular Monitoring
Obtain cardiac history and physical examination before initiating treatment; monitor blood pressure and heart rate at each visit. 8, 2, 6
- Atomoxetine causes statistically but not clinically significant increases in heart rate and blood pressure 8, 3
- Generally should not be used in patients with serious structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm abnormalities 6
- Contraindicated in pheochromocytoma, narrow-angle glaucoma, and severe cardiovascular disorders 6
Growth Monitoring
Monitor height and weight at each visit, as atomoxetine is associated with 1-2 cm decrease in expected height, most pronounced in first 1-2 years of treatment. 8, 5
Growth effects diminish by year 3 of treatment. 8
Common Adverse Effects
The most frequent side effects include:
- Decreased appetite, nausea, vomiting, abdominal pain 2, 7, 3
- Headache 2, 7
- Somnolence (especially initially), fatigue 2, 7, 3
- Dizziness 2
These side effects are generally mild to moderate and transient. 7, 3
Titration and Follow-Up Schedule
Conduct weekly check-ins during dose adjustments using parent and teacher rating scales to assess response. 8
Schedule monthly visits until symptoms are stabilized, then transition to maintenance monitoring every 3-6 months. 8
Assess full therapeutic response only after 6-12 weeks, as atomoxetine has delayed onset of action compared to stimulants. 2, 7
Clinical Advantages Over Stimulants
- No abuse potential; not a controlled substance 2, 7, 3
- No symptom rebound upon discontinuation 7, 3
- Continuous 24-hour coverage without peaks and valleys 2, 7
- May cause less sleep disturbance than stimulants 2, 3
- Fewer effects on appetite and growth long-term compared to stimulants 2
When to Switch from Atomoxetine
If atomoxetine is ineffective after 6-12 weeks or poorly tolerated, switch to stimulant medication (methylphenidate or amphetamine derivatives) or consider alternative non-stimulants like extended-release guanfacine or clonidine. 2
Contraindications
Atomoxetine is contraindicated in:
- Hypersensitivity to atomoxetine 6
- Use within 2 weeks of MAOI discontinuation 6
- Narrow-angle glaucoma 6
- Pheochromocytoma or history of pheochromocytoma 6
- Severe cardiovascular disorders 6
Special Populations
Patients with Comorbid Conditions
Atomoxetine efficacy is not affected by presence of comorbid anxiety, oppositional defiant disorder, conduct disorder, or tic disorders, and may improve symptoms of these conditions. 7, 3
CYP2D6 Poor Metabolizers
These patients (approximately 7% of Caucasian population) have 10-fold higher atomoxetine exposure and require dose reduction by 50%. 6, 3