What is the recommended treatment and dosage of atomoxetine (Strattera) for Attention Deficit Hyperactivity Disorder (ADHD)?

Atomoxetine Treatment for ADHD

Recommended Dosing and Administration

Atomoxetine should be initiated at 0.5 mg/kg/day in children and adolescents up to 70 kg (or 40 mg/day in those over 70 kg and adults), then titrated after a minimum of 7-14 days to a target dose of 1.2 mg/kg/day, with a maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 1

Weight-Based Dosing Algorithm

• Children and adolescents ≤70 kg: 1

  • Initial dose: 0.5 mg/kg/day
  • Target dose: 1.2 mg/kg/day
  • Maximum dose: 1.4 mg/kg/day

• Children and adolescents >70 kg and adults: 1

  • Initial dose: 40 mg/day
  • Target dose: 80 mg/day
  • Maximum dose: 100 mg/day

Administration Options

• Atomoxetine can be given as a single daily dose in the morning or evening, or split into two evenly divided doses (morning and late afternoon/early evening) to minimize side effects. 2, 1

• Split dosing may reduce gastrointestinal side effects and initial somnolence, particularly during dose titration. 2

Position in Treatment Algorithm

Stimulant medications (methylphenidate or amphetamines) remain first-line therapy for ADHD due to larger effect sizes, with atomoxetine positioned as second-line treatment in most guidelines. 3, 2

When to Consider Atomoxetine as First-Line

Atomoxetine may be preferred initially in specific clinical scenarios: 2

• Comorbid substance use disorders (no abuse potential)
• Comorbid tic disorders or Tourette syndrome
• Patients requiring 24-hour symptom coverage without stimulant peaks and valleys
• Sleep disturbances caused by stimulants in patients with autism spectrum disorder and ADHD
• Patient or family preference to avoid controlled substances

Critical Monitoring Requirements

Black Box Warning

The FDA mandates close monitoring for suicidal ideation in children and adolescents, especially during the first few months of treatment or with dose changes. 1

• No suicides occurred in clinical trials, but increased risk of suicidal thoughts was observed. 1

Cardiovascular Assessment

Obtain personal and family cardiac history before initiating treatment; perform ECG if risk factors are present. 3

• Monitor blood pressure and heart rate at baseline and regularly during treatment. 3, 2
• Atomoxetine may cause modest increases in heart rate and blood pressure. 3
• Use with caution in patients with hypertension, tachycardia, or cardiovascular disease. 3

Hepatic Monitoring

Discontinue atomoxetine immediately if jaundice or laboratory evidence of liver injury develops; do not restart. 1

• Severe liver injury, though rare, has been reported. 3

Expected Timeline and Efficacy

Atomoxetine has a delayed onset of therapeutic effect requiring 6-12 weeks for full benefit, unlike stimulants which work within hours. 2

• Assess treatment response only after 6-12 weeks of therapy at target dose. 2
• Effect size is smaller than stimulants but provides continuous 24-hour symptom control. 2
• In clinical trials, atomoxetine showed 28-30% reduction in ADHD symptom scores versus 18-20% with placebo in adults. 4

Common Adverse Effects

The most frequent side effects include: 3, 2

• Gastrointestinal: Decreased appetite, nausea, vomiting, abdominal pain
• Neurological: Headache, somnolence (especially early), dizziness, fatigue
• Urological: Urinary hesitancy or retention
• Growth effects: Temporary growth delays in first 1-2 years, with catch-up growth by 2-3 years 3

Gastrointestinal symptoms are particularly common if dose is increased too rapidly; slower titration minimizes these effects. 3

Dose Adjustments Required

CYP2D6 Considerations

In patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) or known CYP2D6 poor metabolizers, initiate at standard dose but titrate to only 50% of the usual target dose. 1

Hepatic Impairment

Moderate hepatic impairment (Child-Pugh Class B): Reduce dose to 50% of normal 1

Severe hepatic impairment (Child-Pugh Class C): Reduce dose to 25% of normal 1

Special Populations

Preschool Children (Ages 4-5 Years)

No nonstimulant medication, including atomoxetine, has sufficient evidence to recommend use in preschool-aged children with ADHD. 3

• Methylphenidate is the only medication with adequate (though still off-label) evidence in this age group. 3

Comorbid Autism Spectrum Disorder

Atomoxetine demonstrates efficacy and acceptable tolerability in children with comorbid ADHD and ASD, particularly when stimulants cause problematic sleep disturbances. 2, 5

• In a retrospective study of 3-6 year-olds with ADHD and ASD, 62.4% showed "very much improved" symptoms at target doses of 1.2-1.8 mg/kg/day. 5
• Discontinuation rate due to adverse events was 17.3%, with all adverse events resolving after cessation. 5

When to Switch or Augment

If atomoxetine is ineffective after 6-12 weeks at target dose or poorly tolerated, switch to a stimulant medication (methylphenidate or amphetamine) or consider alternative nonstimulants like extended-release guanfacine or clonidine. 2

• Extended-release guanfacine and clonidine are FDA-approved for adjunctive use with stimulants. 3
• Limited evidence supports combining atomoxetine with stimulants for augmentation. 3

Key Clinical Pearls

• Atomoxetine is not a controlled substance, simplifying prescription refills and making it appropriate for patients at risk for substance abuse. 6, 4

• Around-the-clock coverage benefits patients needing symptom control for evening studying or homework without additional dosing. 2

• Patient counseling is essential regarding the 6-12 week delay before full therapeutic benefit to prevent premature discontinuation. 2

• Priapism, though rare, requires immediate medical attention if suspected. 1

• Monitor height and weight in pediatric patients throughout treatment due to potential growth effects. 3, 1