What is the recommended protocol for switching from Vyvanse (lisdexamfetamine) to Strattera (atomoxetine)?

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Switching from Vyvanse to Strattera

You can switch directly from Vyvanse (lisdexamfetamine) to Strattera (atomoxetine) without a washout period or cross-taper, starting atomoxetine the day after stopping Vyvanse.

Switching Protocol

Discontinuation of Vyvanse

  • Stop Vyvanse abruptly without tapering, as stimulants do not require gradual discontinuation and withdrawal syndromes are not a significant concern with these medications 1.
  • The last dose of Vyvanse should be taken in the morning as usual 1.

Initiation of Strattera

  • Start atomoxetine the following day after the last Vyvanse dose 2, 3.
  • Begin with the standard starting dose based on body weight 2:
    • For children and adolescents up to 70 kg: Start at 0.5 mg/kg/day for a minimum of 3 days
    • After 3 days, increase to target dose of 1.2 mg/kg/day
    • For children and adolescents over 70 kg and adults: Start at 40 mg/day for a minimum of 3 days
    • After 3 days, increase to target dose of 80 mg/day
  • Atomoxetine can be administered as a single morning dose or split into two evenly divided doses 2, 3.

Critical Timing Considerations

Expect a Therapeutic Gap

  • Atomoxetine takes 2-4 weeks to achieve full therapeutic effect, unlike Vyvanse which works within hours 2, 3.
  • Warn patients that ADHD symptoms will likely worsen during the first 2-4 weeks of the switch 2.
  • This gap is unavoidable and represents the most significant challenge of this switch.

No Overlap Needed

  • Unlike switching between antidepressants or antipsychotics, no cross-taper or overlap period is required when switching from a stimulant to a non-stimulant 4, 5.
  • There is no risk of serotonin syndrome or drug-drug interactions that would necessitate a washout period 2.

Monitoring During Transition

First 4 Weeks

  • Monitor ADHD symptoms weekly during the initial month, as this is when patients are most vulnerable to symptom exacerbation 2, 3.
  • Assess for emergence of atomoxetine side effects including decreased appetite, nausea, somnolence, and abdominal pain 2, 3.
  • Monitor blood pressure and heart rate at baseline and after dose increases, though changes are typically not clinically significant 2.

Efficacy Assessment

  • Evaluate therapeutic response after at least 4 weeks on the target dose of atomoxetine 2, 3.
  • If inadequate response after 4 weeks at target dose, consider dose optimization before declaring treatment failure 2.

Important Caveats

Efficacy Differences

  • Atomoxetine is significantly less effective than Vyvanse (extended-release amphetamine formulation) based on head-to-head comparisons 2, 3.
  • Set realistic expectations with patients that symptom control may not be as robust as with Vyvanse 2, 3.

When This Switch Makes Sense

  • Atomoxetine is particularly appropriate for patients with substance abuse risk, comorbid anxiety or tics, or those who prefer a non-controlled substance 1, 2, 3.
  • Consider this switch for adolescents with diversion concerns or those who need "around-the-clock" symptom coverage without stimulant effects 1, 6.

Alternative Approach

  • If the reason for switching is insurance coverage rather than clinical indication, consider appealing for Vyvanse coverage or trying other covered stimulants (methylphenidate formulations or amphetamine mixed salts) before moving to the less effective non-stimulant option 6.
  • Methylphenidate formulations are first-line alternatives that maintain stimulant efficacy and are generally well-covered by insurance 6.

Metabolizer Status

  • Screen for CYP2D6 inhibitor use (such as paroxetine, fluoxetine) as these significantly increase atomoxetine exposure and side effects 2.
  • Poor CYP2D6 metabolizers (7-10% of Caucasians) will have higher atomoxetine levels and may require dose adjustment 2.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Switching and stopping antidepressants.

Australian prescriber, 2016

Research

Rationale and strategies for switching antipsychotics.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2002

Guideline

Alternative Treatments for ADHD When Vyvanse is Not Covered by Insurance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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