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

Strattera (Atomoxetine) for ADHD: Treatment Recommendations

Strattera (atomoxetine) is an FDA-approved nonstimulant medication for ADHD that 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), titrated to a target dose of 1.2 mg/kg/day (or 80 mg/day), with a maximum of 1.4 mg/kg/day (or 100 mg/day). 1

Positioning in Treatment Algorithm

• Atomoxetine is a second-line medication for ADHD, reserved for situations where stimulants are ineffective, not tolerated, contraindicated, or when there are concerns about substance abuse or medication diversion. 2
• Stimulant medications remain first-line pharmacological treatment due to superior efficacy (effect size ~1.0 for stimulants vs ~0.7 for atomoxetine). 3
• Atomoxetine is significantly less effective than extended-release methylphenidate formulations and extended-release mixed amphetamine salts, though it does not differ significantly from immediate-release methylphenidate. 4, 5

Dosing Protocol

Children and Adolescents (≤70 kg body weight):

• Initial dose: 0.5 mg/kg/day 1
• Target dose: 1.2 mg/kg/day (typically reached after a minimum of 3 days at initial dose) 1
• Maximum dose: 1.4 mg/kg/day 1
• Can be administered as single morning dose or divided into two equal doses (morning and late afternoon/early evening) 1, 4

Children and Adolescents (>70 kg) and Adults:

• Initial dose: 40 mg/day 1
• Target dose: 80 mg/day (after minimum 3 days at initial dose) 1
• Maximum dose: 100 mg/day 1
• Dosing can be once daily or divided into two doses 1, 6

Dose Adjustments Required:

• Hepatic impairment: Reduce dose to 50% of normal in moderate impairment, 25% in severe impairment 1
• CYP2D6 poor metabolizers or concurrent strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine): Initial dose should be maintained for 4 weeks before increasing, with target dose of 80 mg/day (not 1.2 mg/kg/day) 1, 4

Clinical Considerations for Use

Specific Patient Populations Where Atomoxetine is Preferred:

• Adolescents at risk for substance abuse or with active substance use concerns 2, 3
• Patients with comorbid anxiety disorders (atomoxetine does not exacerbate anxiety) 2, 4
• Patients with comorbid tic disorders 4, 7
• Patients or families who refuse controlled substances 8, 6
• Patients requiring medication coverage throughout waking hours into evening (single morning dose provides all-day coverage) 7

Onset and Duration of Action:

• Treatment effects typically not observed until 2-4 weeks after initiation, unlike stimulants which have rapid onset 9
• Duration of action extends throughout waking hours with single morning dose 7
• Continued efficacy demonstrated in long-term studies up to 18 months 7

Mandatory Safety Monitoring

Pre-Treatment Assessment:

• Obtain detailed personal and family cardiac history (sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, long QT syndrome) 2
• Consider ECG if cardiac risk factors present 2
• Screen for bipolar disorder before initiating treatment (atomoxetine may precipitate manic episode) 1
• In adolescents, assess for substance abuse symptoms 3

Ongoing Monitoring Requirements:

• Monitor for suicidal ideation closely, especially in first few months (FDA black box warning for increased suicidal thoughts in children/adolescents) 1, 4
• Monitor blood pressure and heart rate at each visit (atomoxetine causes mild increases in both) 2
• Assess weight at each visit (decreased appetite is common; growth delays may occur in first 1-2 years) 2
• Monitor for hepatotoxicity (discontinue immediately if jaundice or laboratory evidence of liver injury) 1
• Assess for urinary hesitancy/retention 1
• Monitor for priapism (rare but requires immediate medical attention) 1

Common Adverse Effects

Most Frequent Side Effects:

• Gastrointestinal: Nausea, abdominal pain, vomiting, constipation (especially if dose increased too rapidly) 2, 4
• Appetite/Weight: Decreased appetite, initial weight loss 2, 4
• Neurological: Somnolence (particularly early in treatment), headache, dizziness 2, 4
• Cardiovascular: Modest increases in heart rate (1-2 bpm) and blood pressure (1-4 mmHg) 2
• Other: Dry mouth, irritability 2, 6

Critical Safety Concerns:

• Suicidal ideation (monitor closely, particularly in first months) 1, 4
• Severe liver injury (extremely rare; discontinue if occurs) 1, 4
• Cardiovascular effects (generally mild but monitor in patients with pre-existing conditions) 2, 1
• Emergence of psychotic or manic symptoms (consider discontinuation) 1
• Aggressive behavior or hostility (monitor for appearance or worsening) 1

Discontinuation

• No evidence of rebound symptoms or acute discontinuation syndrome 7
• Can be stopped abruptly without tapering (unlike guanfacine/clonidine) 7
• Modest increases in heart rate and blood pressure gradually decrease on cessation 8, 6

Adjunctive Therapy

• Atomoxetine may be used in combination with stimulant medications when stimulant monotherapy is insufficient, though this is off-label with limited evidence 2
• Behavioral therapy has positive effects when combined with atomoxetine for core ADHD symptoms and comorbid conditions 3

Key Advantages Over Stimulants

• No abuse potential or risk of diversion (not a controlled substance) 4, 8, 6
• Convenient repeat prescriptions during long-term treatment 8, 6
• May be less likely to exacerbate sleep problems compared to methylphenidate 4
• Does not worsen tics or anxiety 4, 7
• Single daily dosing provides all-day symptom coverage 7

Critical Pitfalls to Avoid

• Do not expect immediate response (allow 2-4 weeks to assess efficacy, unlike stimulants) 9
• Do not increase dose too rapidly (increases gastrointestinal side effects) 2
• Do not use in patients taking MAOIs or within 2 weeks of MAOI discontinuation 1
• Do not ignore cardiac history (obtain before starting; consider ECG if risk factors present) 2
• Do not restart if hepatotoxicity occurs 1
• Do not use as first-line in preschool children (insufficient evidence in ages 4-5 years) 2, 3