What is the initial dose of atomoxetine (Strattera) for a patient who has not responded to Adderall (amphetamine and dextroamphetamine) or methylphenidate?

Atomoxetine Dosing After Stimulant Failure

For patients who have not responded to Adderall or methylphenidate, start atomoxetine at 40 mg once daily if the patient weighs over 70 kg (adults and larger adolescents), or 0.5 mg/kg/day for those under 70 kg. 1

Initial Dosing Strategy

For Adults and Adolescents Over 70 kg:

• Start at 40 mg once daily 1
• Increase after a minimum of 3 days to a target dose of 80 mg/day 1
• Can be given as a single morning dose or split into morning and late afternoon/evening doses 1
• After 2-4 additional weeks, may increase to maximum of 100 mg/day if optimal response not achieved 1

For Children and Adolescents Under 70 kg:

• Start at approximately 0.5 mg/kg/day 2, 1
• Increase after minimum of 3 days to target of 1.2 mg/kg/day 1
• Maximum dose should not exceed 1.4 mg/kg/day or 100 mg daily, whichever is less 2

Critical Titration Principles

Slow, gradual dose escalation is essential to minimize adverse effects and avoid behavioral activation. 2

• Maintain initial dose for at least 1-2 weeks before increasing 2
• Increase by small increments (typically 10-25 mg) no more frequently than every 1-2 weeks 2
• Rapid dose increases can cause behavioral activation, agitation, motor restlessness, insomnia, impulsiveness, and aggression, particularly in younger patients 2

Important Clinical Considerations

Delayed Onset of Action:

Unlike stimulants which work within hours, atomoxetine requires 6-12 weeks to achieve full therapeutic effect 3. Set appropriate expectations with patients about this delayed response timeline.

Dosing Flexibility:

• Can be taken with or without food 1
• May split total daily dose into morning and evening to reduce adverse effects 3
• Can even give entire dose in evening if needed 3
• Do not open capsules; must be swallowed whole 1

Special Populations Requiring Dose Adjustment:

If patient is taking strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) or is a known CYP2D6 poor metabolizer:

• Start at 0.5 mg/kg/day for patients under 70 kg 1
• Start at 40 mg/day for patients over 70 kg 1
• Only increase to usual target dose after 4 weeks if symptoms fail to improve and initial dose is well tolerated 1

For hepatic impairment:

• Moderate impairment (Child-Pugh Class B): Reduce initial and target doses to 50% of normal 1
• Severe impairment (Child-Pugh Class C): Reduce to 25% of normal dose 1

Safety Monitoring

Monitor closely for suicidality, clinical worsening, and unusual behavioral changes, especially during the first few months and at dose changes 2. This is a black box warning consideration.

Common adverse effects include nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence 2. These are generally less severe than with alpha-2 agonists like clonidine or guanfacine 3.

Evidence for Use After Stimulant Failure

Atomoxetine is specifically recommended as second-line treatment when stimulants fail or are not tolerated 3. In one head-to-head trial, 43% of methylphenidate non-responders subsequently responded to atomoxetine 4, demonstrating that stimulant failure does not predict atomoxetine failure.

The medication can be discontinued without tapering 1, though symptoms typically return upon discontinuation 3.