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

Atomoxetine for ADHD: Treatment Recommendations and Dosing

Atomoxetine is an FDA-approved nonstimulant medication for ADHD in children ≥6 years and adolescents, with an initial dose of 0.5 mg/kg/day, titrated to a target of 1.2 mg/kg/day (maximum 1.4 mg/kg or 100 mg/day in patients ≤70 kg), and is particularly indicated when stimulants are contraindicated, ineffective, or in patients with comorbid anxiety, tics, or substance abuse risk. 1

Age-Specific Treatment Positioning

Preschool Children (Ages 4-5 Years)

• No nonstimulant medication, including atomoxetine, has sufficient evidence for use in preschool-aged children with ADHD. 2
• Methylphenidate remains the only medication with adequate (though still off-label) evidence in this age group. 2

Elementary School-Aged Children (Ages 6-11 Years)

• FDA-approved medications for ADHD should be prescribed, with stimulants as first-line and atomoxetine as an alternative nonstimulant option. 2
• The evidence hierarchy is: stimulants (strongest) > atomoxetine > extended-release guanfacine > extended-release clonidine. 2
• Atomoxetine is particularly appropriate for children with comorbid anxiety disorders, tics, Tourette syndrome, or substance abuse risk. 2

Adolescents (Ages 12-18 Years)

• FDA-approved ADHD medications should be prescribed with the adolescent's assent, with atomoxetine serving as an effective nonstimulant alternative. 2

Dosing Algorithm

Standard Dosing (Children and Adolescents)

For patients ≤70 kg: 1

• Initial dose: 0.5 mg/kg/day
• Target dose: 1.2 mg/kg/day (typically reached after minimum 3 days at initial dose)
• Maximum dose: 1.4 mg/kg/day

For patients >70 kg and adults: 1

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

Dosing Schedule Options

• Can be administered once daily in the morning OR divided into two doses (morning and late afternoon/early evening). 1
• Once-daily dosing has demonstrated equivalent efficacy to divided dosing. 1

Dose Adjustments Required

Hepatic impairment: 1

• Moderate impairment (Child-Pugh Class B): Reduce to 50% of normal dose
• Severe impairment (Child-Pugh Class C): Reduce to 25% of normal dose

CYP2D6 poor metabolizers or concurrent strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): 1

• Reduce target dose to 0.5 mg/kg/day in children ≤70 kg
• Reduce target dose to 40 mg/day in patients >70 kg
• Only increase to usual target doses if symptoms fail to improve after 4 weeks AND initial dose is well-tolerated

Expected Response Timeline

Critical counseling point: Atomoxetine has a gradual onset of action, unlike stimulants. 3

• Initial response may appear within 1 week, but median time to response is 23 days. 3
• Robust response (≥40% symptom reduction) often requires 3+ months of treatment. 3
• Response at 4 weeks may predict 6-9 week outcomes, but probability of robust response continues increasing beyond 6-9 weeks. 3

Safety Monitoring Requirements

Cardiovascular Assessment

Before initiating atomoxetine: 2

• Obtain personal history of cardiac symptoms (chest pain, syncope, palpitations)
• Obtain family history of sudden death, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, long QT syndrome
• If ANY risk factors present: obtain ECG and consider cardiology referral if abnormal

During treatment: 2

• Monitor heart rate and blood pressure (atomoxetine causes mild increases: 1-2 bpm HR, 1-4 mmHg BP on average)
• 5-15% of patients experience more substantial increases requiring monitoring. 2

Critical Safety Warnings

FDA Black Box Warning - Suicidal Ideation: 1

• Increased risk in children and adolescents
• Monitor closely for suicidality, clinical worsening, and unusual behavioral changes, especially early in treatment
• No completed suicides occurred in clinical trials. 1

Severe Liver Injury: 1

• Extremely rare but documented
• Discontinue immediately and do not restart if jaundice or laboratory evidence of liver injury develops

Other Important Adverse Effects: 2

• Initial somnolence and gastrointestinal symptoms (especially if titrated too rapidly)
• Decreased appetite
• Growth delays in first 1-2 years (returns to expected trajectory by 2-3 years, primarily in children taller/heavier than average at baseline)
• Urinary hesitancy/retention
• Priapism (rare but requires immediate medical attention)

Titration Caution

Increase dosage slowly to minimize gastrointestinal side effects and somnolence. 2 Wait minimum 3 days at initial dose before increasing. 1

Adjunctive Therapy Considerations

• Atomoxetine can be used off-label in combination with stimulants when monotherapy provides insufficient response. 2
• Limited evidence supports this combination approach for augmentation. 2
• Extended-release guanfacine and extended-release clonidine have stronger FDA-approved evidence for adjunctive use with stimulants. 2

Contraindications

Absolute contraindications: 1

• Hypersensitivity to atomoxetine
• Use within 2 weeks of MAOI discontinuation
• Narrow-angle glaucoma
• Pheochromocytoma or history thereof
• Severe cardiovascular disorders that might deteriorate with increases in heart rate/blood pressure

Special Populations

Patients with comorbid conditions: 4

• Atomoxetine appears well-tolerated in children ages 3-6 with ADHD and autism spectrum disorder (though this is off-label use below age 6)
• Preliminary data suggest benefit for comorbid anxiety and oppositional symptoms. 5

Geographic variations in maximum dosing: 2

• Japan: 120 mg/day or 1.8 mg/kg/day
• Malaysia: 100 mg/day
• India: 100 mg/day
• South Korea: 1.4 mg/kg/day

Efficacy Data

• Effect sizes versus placebo: 0.6-1.3 at 6-18 weeks. 3
• Doses of 1.2 mg/kg/day and 1.8 mg/kg/day show equivalent efficacy; 1.8 mg/kg/day provides no additional benefit. 6
• The 0.5 mg/kg/day dose shows intermediate efficacy between placebo and higher doses. 6
• Discontinuation rate due to adverse events: <5% in registration trials. 6, 5