What are the considerations and potential side effects for a child, adolescent, or adult with Attention Deficit Hyperactivity Disorder (ADHD) when using Strattera (atomoxetine)?

Strattera (Atomoxetine) for ADHD: Key Considerations and Side Effects

Atomoxetine is a second-line, non-stimulant medication for ADHD that is FDA-approved for children (6+ years), adolescents, and adults, but carries a black box warning for increased suicidal ideation in pediatric patients and requires 6-12 weeks to achieve full therapeutic effect. 1, 2

Critical Safety Warnings

Suicidal Ideation Risk

• The FDA mandates a black box warning: atomoxetine increases the risk of suicidal ideation in children and adolescents (0.4% vs 0% with placebo). 1, 3
• Monitor patients closely, especially during the first few months of treatment or with dose changes. 2
• Families and caregivers must be advised to watch for suicidal thinking, clinical worsening, or unusual behavioral changes. 1

Hepatotoxicity

• Extremely rare cases of hepatitis have occurred; discontinue immediately if jaundice or clinically significant liver dysfunction develops. 3

Cardiovascular Effects

• Atomoxetine causes mild increases in heart rate and blood pressure, which are generally clinically insignificant but require monitoring. 3
• 5-10% of pediatric patients experience potentially clinically important changes in cardiovascular parameters. 3
• Obtain baseline blood pressure and heart rate before starting treatment. 2

Positioning in Treatment Algorithm

Stimulants remain first-line therapy due to larger effect sizes (1.0 vs 0.7 for atomoxetine). 4, 2

When to Consider Atomoxetine First-Line:

• Patients with comorbid substance use disorders or at risk for stimulant diversion (particularly adolescents). 4, 2
• Patients with tic disorders or Tourette's syndrome. 2
• Patients who prefer non-controlled substances. 5, 6
• Patients requiring 24-hour symptom coverage without stimulant "peaks and valleys." 2

Dosing and Administration

Pediatric Dosing (Children/Adolescents ≤70 kg):

• Start: 0.5 mg/kg/day 2
• Target: 1.2 mg/kg/day 2
• Maximum: 1.4 mg/kg/day or 100 mg/day, whichever is lower 2, 1
• Titrate every 7-14 days. 2

Adult Dosing (>70 kg):

• Start: 40 mg/day 2
• Target: 80-100 mg/day 2
• Maximum: 100 mg/day 2

Administration Options:

• Can be given once daily (morning or evening) or split into two evenly divided doses to reduce side effects. 2, 3
• Take with or without food. 1
• Swallow capsules whole—do not crush, chew, or open. 1
• If capsule contents contact skin or eyes, wash immediately and contact physician. 1

Common Side Effects

Gastrointestinal (Most Common):

• Decreased appetite, nausea, vomiting, abdominal pain (24.1% in pediatric studies). 3, 5
• These are particularly prominent if dosage is increased too rapidly. 4, 3
• Mitigation strategy: Split dosing or evening-only administration. 3

Neuropsychiatric:

• Initial somnolence (common early in treatment). 4, 3
• Headache, dizziness, fatigue. 2, 5
• Aggression or hostility (12.8% in young children). 7
• Increased hyperactivity (9.0% in young children). 7

Other Common Effects:

• Dry mouth (adults). 5, 6
• Constipation (adults). 5, 6
• Sexual side effects (adults). 1
• Urinary hesitancy or retention. 1

Rare but Serious:

• Priapism: Erections lasting >4 hours require immediate medical attention. 1

Growth and Development Considerations

• Growth delays may occur in the first 1-2 years of treatment, with return to expected measurements after 2-3 years. 3
• Atomoxetine has fewer appetite and growth problems compared to stimulants. 2, 3
• Monitor height and weight regularly during treatment. 1

Pharmacogenetic Considerations

Approximately 7% of Caucasians and 2% of African Americans are CYP2D6 poor metabolizers. 2

• Poor metabolizers experience 10-fold higher drug exposure and 24-hour half-life (vs 5.2 hours in extensive metabolizers). 2, 8
• This results in significantly higher rates of adverse effects. 3
• CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) produce similar effects in extensive metabolizers. 8

Onset of Action and Monitoring

Critical expectation-setting: Full therapeutic effects require 6-12 weeks, unlike stimulants which work within hours. 2

• Assess response only after this timeframe. 2
• This delayed onset is a major limitation compared to stimulants. 2

Monitoring Schedule:

• Baseline: Blood pressure, heart rate, liver function, psychiatric symptoms. 2, 3
• Follow-up: Vital signs at each visit, height/weight regularly, suicidal ideation monitoring (especially first few months). 2, 1

Special Populations

Preschool Children (4-5 years):

• Not FDA-approved for children under 6 years. 4
• Behavior therapy should be initiated first in this age group. 4

Adolescents:

• Particular concern for diversion and substance abuse. 4
• Atomoxetine is preferred when abuse potential is a concern. 4
• Consider longer-acting coverage for driving safety. 4

Comorbid Conditions:

• Effective in patients with comorbid anxiety, tics, or oppositional-defiant disorder. 9, 5
• Recent data support efficacy in young children (3-6 years) with ADHD and autism spectrum disorder, though close monitoring is essential. 7

Discontinuation

Atomoxetine can be discontinued without tapering, though gradual tapering over 1-2 weeks is recommended to minimize potential adverse effects. 10

• No evidence of rebound symptoms or acute discontinuation syndrome. 9, 5
• Monitor for return of ADHD symptoms during and after discontinuation. 10
• Continue cardiovascular monitoring during tapering. 10
• Allow 1-week washout before initiating another non-stimulant. 10

Combination Therapy

Only extended-release guanfacine and extended-release clonidine have FDA approval for adjunctive use with ADHD medications. 4

• Clonidine can be added to atomoxetine for persistent hyperactivity, aggression, or sleep disturbances. 2
• Start clonidine at 0.05 mg at bedtime, never exceeding 0.3 mg/day. 2
• Obtain baseline cardiovascular assessment and rule out family history of sudden death, fainting, or arrhythmias before adding clonidine. 2

Key Clinical Pitfalls to Avoid

• Do not expect immediate response—counsel patients about 6-12 week onset. 2
• Do not increase dose too rapidly—this causes gastrointestinal side effects. 3
• Do not ignore suicidal ideation screening, especially in first few months. 1
• Do not crush or open capsules—risk of eye/skin irritation. 1
• Do not forget cardiovascular monitoring throughout treatment. 3
• Do not assume poor response before 6-12 weeks of adequate dosing. 2