Atomoxetine Dosing and Treatment Protocol for ADHD
Recommended Dosing Regimen
Atomoxetine should be initiated at 0.5 mg/kg/day in children and adolescents up to 70 kg (or 40 mg/day for those over 70 kg and adults), then titrated to a target dose of 1.2 mg/kg/day, with a maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower. 1, 2
Weight-Based Dosing Algorithm
For 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 interval: Increase dose every 7-14 days 1
For children and adolescents >70 kg and adults:
Administration Options
Atomoxetine can be given as a single daily dose (morning or evening) or split into two evenly divided doses to minimize gastrointestinal side effects. 1, 2, 3
Position in Treatment Algorithm
Stimulant medications (methylphenidate or amphetamines) remain first-line therapy for ADHD due to larger effect sizes, with atomoxetine positioned as second-line therapy. 1, 4
When to Consider Atomoxetine as First-Line
Atomoxetine should be considered as first-line treatment in specific clinical scenarios:
- Comorbid substance use disorders (stimulants carry abuse potential) 4
- Comorbid tic disorders or Tourette syndrome 4
- Comorbid anxiety disorders 4
- Comorbid autism spectrum disorder 4, 1
- Patients with sleep disturbances on stimulants 4, 1
- Patients refusing controlled substances 3
Pre-Treatment Assessment
Before initiating atomoxetine, obtain:
- Personal and family cardiac history to identify cardiovascular risk factors 4
- Baseline blood pressure and heart rate (atomoxetine increases both parameters) 4, 2
- Screen for bipolar disorder (atomoxetine may precipitate manic episodes) 2
- Assess for narrow-angle glaucoma (absolute contraindication) 2
- Assess for pheochromocytoma (absolute contraindication) 2
- Obtain baseline liver function tests (rare but serious hepatotoxicity reported) 4, 2
If cardiac risk factors are present, obtain an ECG and consider cardiology referral before starting treatment. 4
Monitoring During Treatment
Timeline for Response Assessment
Atomoxetine has a delayed onset of action requiring 6-12 weeks for full therapeutic effect, unlike stimulants which work within hours. 1, 5
Assess treatment response after 6-12 weeks of therapy at target dose. 1
Ongoing Monitoring Parameters
At each follow-up visit, monitor:
- Blood pressure and heart rate (expect modest increases) 4, 1, 2
- Suicidal ideation (FDA black box warning for increased risk in children/adolescents) 4, 1, 2
- Aggressive behavior or hostility (may emerge or worsen) 2
- Height and weight in pediatric patients (growth delays observed in first 1-2 years) 4, 1
- Liver function if jaundice or symptoms of hepatotoxicity develop 4, 2
Common Adverse Effects and Management
The most common side effects include:
- Decreased appetite, nausea, vomiting, abdominal pain (minimize by split dosing or taking with food) 4, 1, 2
- Initial somnolence (consider evening dosing) 4, 1
- Headache and dizziness 1, 2
- Dry mouth, constipation 3
- Urinary hesitancy or retention 2
These effects are typically mild to moderate and transient, often resolving with continued treatment. 5, 6
Dose Adjustments for Special Populations
Reduce atomoxetine dose by 50% in:
- Patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) 2
- Known CYP2D6 poor metabolizers 2
Reduce atomoxetine dose in hepatic impairment:
- Moderate hepatic impairment: Reduce to 50% of normal dose 2
- Severe hepatic impairment: Reduce to 25% of normal dose 2
Contraindications
Absolute contraindications to atomoxetine:
- Use within 14 days of MAOI discontinuation 2
- Narrow-angle glaucoma 2
- Pheochromocytoma or history thereof 2
- Severe cardiovascular disorders that may deteriorate with increased heart rate/blood pressure 2
- Hypersensitivity to atomoxetine 2
Adjunctive Therapy Considerations
If stimulant monotherapy provides partial response, atomoxetine can be added as adjunctive therapy, though evidence is limited compared to alpha-2 agonists (guanfacine, clonidine). 4
Extended-release guanfacine and clonidine have stronger evidence for adjunctive use with stimulants and are FDA-approved for this indication. 4
Clinical Pearls and Pitfalls
Key advantages of atomoxetine:
- Provides 24-hour symptom coverage without peaks and valleys 1
- No abuse potential (not a controlled substance) 3
- Can be prescribed with refills (more convenient than stimulants) 3
- May improve comorbid anxiety symptoms 4
Critical pitfalls to avoid:
- Do not expect immediate response like stimulants; counsel patients about 6-12 week delay 1, 5
- Do not abruptly discontinue if switching to another medication; taper is not required but monitor for symptom recurrence 2
- Do not ignore suicidal ideation screening, especially in first few months or after dose changes 4, 2
- Do not restart atomoxetine if jaundice or laboratory evidence of liver injury develops 2
- Do not use in patients with structural cardiac abnormalities without cardiology clearance 2
Special Population: Preschool Children (Age 4-5 Years)
Atomoxetine is not recommended for preschool-aged children due to insufficient evidence in this population. 4
Methylphenidate is the preferred medication for preschool ADHD if behavioral interventions fail, though this remains off-label. 4