Strattera (Atomoxetine) Dosing and Treatment Guidelines for ADHD
Atomoxetine is a second-line, non-stimulant medication for ADHD that should be started at 0.5 mg/kg/day and titrated to a target dose of 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg/day, whichever is lower), with full therapeutic effects taking 6-12 weeks to develop. 1, 2, 3
Position in Treatment Algorithm
Stimulants remain first-line therapy due to their larger effect sizes (~1.0 for stimulants vs ~0.7 for atomoxetine), with atomoxetine positioned as second-line treatment. 4, 1 However, atomoxetine should be considered as first-line in specific clinical scenarios: 1
- Patients with comorbid substance use disorders or at risk for substance abuse 4, 1
- Patients with comorbid tic disorders or Tourette's syndrome 4, 1
- Adolescents at risk for medication diversion 4
- Patients who prefer not to take a controlled substance 5, 6
- Patients with comorbid anxiety disorders 5, 7
- Patients experiencing significant sleep disturbances on stimulants 1
Age-Specific Dosing Guidelines
Children and Adolescents (6-18 years)
For patients weighing ≤70 kg: 1, 2, 3
- Initial dose: 0.5 mg/kg/day
- Target dose: 1.2 mg/kg/day (after minimum 3 days)
- Maximum dose: 1.4 mg/kg/day
For patients weighing >70 kg and adults: 1, 3
- Initial dose: 40 mg/day
- Target dose: 80 mg/day
- Maximum dose: 100 mg/day
Titration schedule: Increase dose every 7-14 days based on response and tolerability. 1
Preschool-Aged Children (<6 years)
Atomoxetine is NOT recommended for preschool-aged children (4-5 years) as it has not received sufficient rigorous study in this population. 4, 2 For this age group, evidence-based behavioral therapy is first-line, with methylphenidate considered only for moderate-to-severe dysfunction unresponsive to behavioral interventions. 4
Administration Options
Atomoxetine can be administered as: 1, 3, 5
- Once-daily dosing: Single morning or evening dose
- Split dosing: Two evenly divided doses (morning and evening) to reduce side effects
Evening dosing may be preferred when somnolence is problematic, while morning dosing provides coverage throughout the day and evening for studying. 1
Dose Adjustments for Special Populations
CYP2D6 Poor Metabolizers or Strong CYP2D6 Inhibitors
Reduce the target dose when atomoxetine is used with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) or in patients known to be CYP2D6 poor metabolizers, as these patients have 10-fold higher plasma concentrations. 1, 3, 5
Hepatic Impairment
Dose reduction is required in patients with hepatic insufficiency due to increased atomoxetine exposure. 3, 5
Critical Safety Monitoring
Black Box Warning: Suicidal Ideation
The FDA requires close monitoring for suicidal ideation, particularly in children and adolescents during the first few months of treatment or with dose changes. 1, 2, 3 No suicides occurred in clinical trials, but increased risk of suicidal ideation was demonstrated in meta-analyses. 3, 5
Cardiovascular Monitoring
Obtain personal and family cardiac history before starting treatment. 8, 3 Monitor for: 1, 3
- Blood pressure and heart rate increases (modest but consistent)
- Orthostatic hypotension and syncope
- Consider ECG if cardiac risk factors are present
Atomoxetine should generally not be used in patients with serious structural cardiac abnormalities, cardiomyopathy, or serious heart rhythm abnormalities. 3
Hepatotoxicity
Discontinue atomoxetine immediately if jaundice or laboratory evidence of liver injury develops, and do not restart. 3 Rare cases of serious liver injury have been reported postmarketing. 5
Growth Monitoring
Monitor height and weight regularly in pediatric patients, as atomoxetine has been linked to growth delays in the first 1-2 years of treatment, though growth typically normalizes long-term. 2, 5
Common Adverse Effects
Most frequent side effects include: 1, 2, 3, 5
- Decreased appetite
- Nausea and abdominal pain
- Headache
- Somnolence (especially initially)
- Fatigue
- Vomiting
Less common but important: 3, 5
- Urinary hesitancy/retention
- Priapism (requires prompt medical attention)
- Allergic reactions including anaphylaxis
Psychiatric Monitoring
Screen for bipolar disorder before initiating treatment, as atomoxetine may precipitate manic episodes. 4, 3 Monitor for: 3
- Emergence of new psychotic or manic symptoms
- Aggressive behavior or hostility (especially early in treatment)
- Clinical worsening or unusual behavior changes
Timeline for Therapeutic Response
Full therapeutic effects require 6-12 weeks, unlike stimulants which have rapid onset. 1 This delayed onset requires patience during initial treatment and means assessment of response should occur after 6-12 weeks, not earlier. 1
Advantages Over Stimulants
Atomoxetine provides "around-the-clock" symptom control without the peaks and valleys of stimulant medications. 1 Additional benefits include: 1, 5, 6
- No abuse potential (not a controlled substance)
- No risk of diversion
- May improve sleep compared to stimulants
- Fewer effects on appetite and growth long-term
- Effective for comorbid anxiety
When to Consider Switching
If atomoxetine is ineffective after 6-12 weeks or poorly tolerated, consider: 1
- Trial of stimulant medication (methylphenidate or amphetamine derivatives)
- Extended-release guanfacine or clonidine
- Combination therapy with stimulants (atomoxetine as adjunctive)
Discontinuation
Atomoxetine can be discontinued without tapering, as there is no evidence of rebound symptoms or acute discontinuation syndrome. 5, 9 This contrasts with alpha-2 agonists which require tapering. 8