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

Atomoxetine Treatment for ADHD

Atomoxetine is FDA-approved as a selective norepinephrine reuptake inhibitor for ADHD treatment in children, adolescents, and adults, with recommended dosing starting at 0.5 mg/kg/day (or 40 mg/day for patients >70 kg) and titrating to a target of 1.2 mg/kg/day, with a maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 1, 2

Positioning in Treatment Algorithm

• Stimulants remain first-line therapy due to larger effect sizes compared to atomoxetine, which is positioned as second-line treatment 1
• Consider atomoxetine as first-line in specific clinical scenarios:
  • Patients with comorbid substance use disorders 1
  • Patients with tic disorders or Tourette's syndrome 1
  • Patients experiencing sleep disturbances from stimulants 1
  • Patients who prefer a non-controlled substance 3, 4

Dosing Protocol

Children and Adolescents ≤70 kg:

• Initial dose: 0.5 mg/kg/day 1, 2
• Target dose: 1.2 mg/kg/day 1, 2
• Maximum dose: 1.4 mg/kg/day 1, 2
• Titration schedule: Increase every 7-14 days based on clinical response 1

Children and Adolescents >70 kg and Adults:

• Initial dose: 40 mg/day 1, 2
• Target dose: 80 mg/day 1, 2
• Maximum dose: 100 mg/day 1, 2

Administration Options:

• Once-daily dosing (morning or evening) is effective and convenient 1, 2
• Split dosing (morning and late afternoon/early evening) may reduce side effects initially 1
• The 1.8 mg/kg/day dose provides no additional benefit over 1.2 mg/kg/day 2, 5

Dose Adjustments Required

Reduce dose by 50% in the following situations:

• Moderate hepatic impairment 2
• Concomitant use of strong CYP2D6 inhibitors 1, 2
• Known CYP2D6 poor metabolizers 1, 2

Reduce dose by 75% in severe hepatic impairment 2

Clinical Advantages

• Provides 24-hour symptom coverage without the peaks and valleys of stimulants 1
• No abuse potential and not a controlled substance, allowing easier prescription refills 3, 4
• Fewer effects on appetite and growth compared to stimulants during long-term treatment 1
• Effective in comorbid conditions including autism spectrum disorder with ADHD 1, 6

Critical Monitoring Requirements

Black Box Warning:

• Increased risk of suicidal ideation in children and adolescents 1, 2
• Monitor closely during the first few months and with dose changes 1, 2
• No suicides occurred in clinical trials 2

Cardiovascular Monitoring:

• Assess for cardiovascular disease before initiating treatment 2
• Monitor blood pressure and heart rate at baseline and regularly during treatment 1, 2
• Do not use in patients with serious structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm abnormalities 2
• Modest increases in heart rate and blood pressure are common but generally well tolerated 3, 4

Hepatic Monitoring:

• Discontinue immediately if jaundice or laboratory evidence of liver injury develops 2
• Do not restart atomoxetine in patients who develop liver injury 2

Other Monitoring:

• Screen for bipolar disorder prior to starting treatment 2
• Monitor for emergence of psychotic or manic symptoms 2
• Watch for aggressive behavior or hostility, especially early in treatment 2
• Monitor growth (height and weight) in pediatric patients 2

Common Adverse Effects

The most frequent side effects include:

• Decreased appetite, nausea, vomiting, and abdominal pain 1, 3, 4
• Headache and somnolence (particularly early in treatment) 1
• Dry mouth, constipation, and dizziness 3, 4
• Urinary hesitancy or retention 2
• Sexual dysfunction in adults 3, 4

Discontinuation rates due to adverse events range from 2.8% to 9.3% in clinical trials 3, 4, 7

Timeline for Efficacy Assessment

• Full therapeutic effects require 6-12 weeks to develop 1
• Assess response after 6-12 weeks before determining treatment failure 1
• This delayed onset is a key disadvantage compared to stimulants, which work within hours 1

Efficacy Data

• Mean symptom reduction of 28-30% on ADHD rating scales versus 18-20% with placebo in adults 3, 4
• Doses of 1.2 mg/kg/day and 1.8 mg/kg/day showed superior efficacy to placebo in pediatric trials 2, 5
• The 0.5 mg/kg/day dose was not superior to placebo 2, 5
• Continued efficacy demonstrated in extension studies up to 34 weeks 3, 4

Alternative Options if Ineffective

If atomoxetine fails after adequate trial (6-12 weeks at target dose):

• Switch to stimulant medication (methylphenidate or amphetamine derivatives) 1
• Consider alpha-2 agonists (extended-release guanfacine or clonidine), particularly if sleep disturbances are prominent 1

Special Populations

Autism Spectrum Disorder with ADHD:

• Atomoxetine at 1.2-1.8 mg/kg/day appears well tolerated and effective in children aged 3-6 years with comorbid ASD and ADHD 6
• Close monitoring remains essential in this population 6

Patients with Sleep Disturbances:

• Atomoxetine is particularly useful when stimulants cause insomnia 1
• Can be dosed in the evening if needed 1

Contraindications

Absolute contraindications include:

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