Atomoxetine Treatment for ADHD: Dosage and Recommendations
Atomoxetine (Strattera) is recommended as a second-line treatment for ADHD with a maximum recommended dosage of 1.4 mg/kg/day or 100 mg/day (whichever is lower), following a sequential weight-based titration approach. 1
Mechanism of Action and Formulations
- Atomoxetine is a selective norepinephrine reuptake inhibitor that increases both noradrenaline and dopamine in the prefrontal cortex synapses 1
- Available in capsules containing 10,18,25,40,60,80, or 100 mg of atomoxetine hydrochloride and as an oral solution (4 mg/ml) 1
- Primarily metabolized through the cytochrome P450 2D6 (CYP2D6) pathway, with approximately 7% of the population being poor metabolizers 1
Dosing Recommendations
Children and Adolescents
- Initial daily dose: 0.5 mg/kg 1, 2
- Target total daily dose: 1.2 mg/kg 1, 2
- Maximum daily dose: 1.4 mg/kg (not to exceed 100 mg/day) 1, 2
Adults and Children over 70 kg
Administration Schedule
- Can be administered either as a single daily morning dose or split into two evenly divided doses (morning and late afternoon) 1, 3
- Once-daily morning dosing has been shown to be effective into the evening 3
- For patients experiencing side effects, splitting the dose may help reduce adverse effects 1
Treatment Algorithm
First-line treatment: Stimulants (methylphenidate or amphetamines) are generally recommended as first-line therapy due to their larger effect sizes 1
When to use atomoxetine as first-line:
When to use atomoxetine as second-line:
Monitoring and Safety Considerations
- Suicidal ideation: Monitor closely for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months of treatment or with dose changes (FDA black box warning) 1
- Cardiovascular effects: Check pulse and blood pressure; use with caution in patients with hypertension, tachycardia, or cardiovascular disease 1
- Liver function: Discontinue if jaundice or laboratory evidence of liver injury develops 2
- Growth: Monitor height and weight in pediatric patients 1
- CYP2D6 interactions: Dose adjustment may be necessary with strong CYP2D6 inhibitors (e.g., some SSRIs) or in known CYP2D6 poor metabolizers 1, 2
Common Adverse Effects
- Most common adverse effects in children and adolescents: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence 1
- In adults: dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, sexual problems, and palpitations 5, 4
- Atomoxetine generally shows lower effects on appetite and growth compared to stimulants 1
Efficacy and Onset of Action
- Atomoxetine has medium effect sizes for reducing ADHD symptoms, smaller than those of stimulants 1
- Treatment effects typically take 6-12 weeks to fully manifest, unlike stimulants which have a rapid onset 1
- Provides "around-the-clock" effects rather than time-limited coverage 1
- Effective in improving both ADHD core symptoms and quality of life 3
Special Considerations
- Not recommended as first-line treatment for preschool-aged children (4-5 years) due to insufficient rigorous study in this population 1
- May be particularly beneficial in patients with ADHD and comorbid conditions such as anxiety disorders, tic disorders, or substance use disorders 1, 3
- Discontinuation should be gradual to avoid withdrawal symptoms 1
By following these evidence-based recommendations for atomoxetine treatment in ADHD, clinicians can optimize outcomes while minimizing adverse effects, ultimately improving patients' quality of life and reducing functional impairment.