What is the recommended initial dose of Strattera (atomoxetine) based on patient weight and age, and how should it be adjusted in hepatic or renal impairment?

Starting Dose of Strattera (Atomoxetine)

For adults and children over 70 kg, start atomoxetine at 40 mg orally once daily; for children and adolescents up to 70 kg, start at approximately 0.5 mg/kg/day. 1, 2

Weight-Based Dosing Algorithm

Children and Adolescents ≤70 kg

• Initial dose: 0.5 mg/kg/day (approximately 40 mg for most patients) 1, 2
• Titration schedule: Increase after a minimum of 7-14 days to 60 mg daily, then to 80 mg daily 1, 2
• Target dose: 1.2 mg/kg/day 2, 3, 4
• Maximum dose: The lesser of 1.4 mg/kg/day or 100 mg/day 1, 2, 5

Adults and Children >70 kg

• Initial dose: 40 mg orally once daily 1, 2, 5
• Titration schedule: Increase every 7-14 days to 60 mg, then 80 mg daily 1, 2
• Target dose: 60-100 mg daily 2, 5
• Maximum dose: 100 mg/day 1, 2, 5

Dosing Frequency Options

Atomoxetine can be administered as a single morning dose or split into two evenly divided doses (morning and late afternoon/early evening). 6, 4, 7 Split dosing may reduce adverse effects, particularly gastrointestinal symptoms and initial somnolence. 5 Evening-only dosing is also an option if daytime sedation is problematic. 5

Hepatic Impairment Adjustments

For patients with moderate hepatic insufficiency (Child-Pugh Class B), reduce the initial and target doses to 50% of the normal dose. 8 For severe hepatic insufficiency (Child-Pugh Class C), reduce to 25% of the normal dose. 8 Hepatic impairment increases atomoxetine exposure significantly due to reduced first-pass metabolism. 8

Renal Impairment Adjustments

No dose adjustment is required for renal impairment, as atomoxetine is primarily metabolized hepatically via CYP2D6, not renally excreted. 8 However, monitor cardiovascular parameters more closely in patients with any significant organ dysfunction. 2

CYP2D6 Poor Metabolizers

Patients who are CYP2D6 poor metabolizers (approximately 7% of Caucasians) will have 10-fold higher steady-state plasma concentrations. 8 While no initial dose adjustment is required, these patients may need lower maintenance doses and experience a longer time to steady state (approximately 5 days vs. 2 days in extensive metabolizers). 8 The half-life extends from 5.2 hours in extensive metabolizers to 21.6 hours in poor metabolizers. 8

Potent CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) will convert extensive metabolizers into phenotypic poor metabolizers, requiring similar dose adjustments. 8

Critical Titration Principles

Maintain the initial dose for at least 7-14 days before increasing, as atomoxetine requires 6-12 weeks to achieve full therapeutic effect, unlike stimulants which work within days. 2, 5, 6 Slow titration minimizes behavioral activation, agitation, and gastrointestinal side effects. 2

Increase doses by small increments (typically 10-20 mg) no more frequently than every 7-14 days. 2 Rapid dose escalation increases the risk of behavioral activation, particularly in younger patients. 2

Baseline and Monitoring Requirements

Before initiating atomoxetine:

• Obtain baseline blood pressure, heart rate, height, and weight 2, 5
• Screen for suicidal ideation and document psychiatric history, as atomoxetine carries an FDA black box warning for increased suicidal ideation in children and adolescents 5, 6, 7
• Obtain detailed cardiac and family cardiac history (syncope, arrhythmias, sudden death, structural heart disease) 2, 9

During treatment:

• Monitor blood pressure and pulse at each visit during titration and quarterly during maintenance 2, 5
• Track height and weight at every visit, particularly in pediatric patients 2, 5, 9
• Systematically assess for suicidal ideation, clinical worsening, and unusual behavioral changes, especially during the first few months or at dose changes 1, 2, 5

Common Pitfalls to Avoid

Do not prescribe atomoxetine first-line when fatigue is a chief complaint, as somnolence and fatigue are among the most common adverse effects and would directly worsen this symptom. 5, 6, 3 Consider stimulants or bupropion instead in this scenario. 5

Do not assume atomoxetine will adequately treat comorbid depression, despite its initial development as an antidepressant—evidence does not support efficacy for depression. 5 If mood symptoms persist after ADHD improvement, add an SSRI. 2, 5

Never abruptly discontinue atomoxetine in patients taking it chronically, though discontinuation is generally well tolerated with low incidence of withdrawal symptoms. 6, 3 Gradual tapering is prudent for any long-term psychotropic medication.

Do not exceed 1.4 mg/kg/day or 100 mg/day, whichever is lower, as higher doses do not improve efficacy and increase adverse effects. 1, 2, 5