Switching from Adderall to Atomoxetine: Protocol and Considerations
When switching from Adderall (amphetamine and dextroamphetamine) to atomoxetine, a cross-tapering approach is recommended to minimize withdrawal symptoms and maintain symptom control during the transition period. 1
Step-by-Step Switching Protocol
Week 1: Initiation Phase
- Continue full dose of Adderall
- Start atomoxetine at 0.5 mg/kg/day (typically as a morning dose)
- Monitor for side effects including nausea, fatigue, and somnolence
Week 2: Cross-Tapering Phase
- Reduce Adderall to half of the original dose
- Increase atomoxetine to 1.2 mg/kg/day (target dose)
- Maximum dose: 1.4 mg/kg/day or 100 mg/day, whichever is lower 2
Weeks 3-7: Atomoxetine Monotherapy
- Discontinue Adderall completely
- Continue atomoxetine at 1.2 mg/kg/day
- Allow 6-8 weeks for full evaluation of atomoxetine efficacy 1
Important Monitoring Parameters
Cardiovascular Monitoring
- Check blood pressure and heart rate at baseline
- Monitor at each dose increase
- Expect small increases in both diastolic and systolic blood pressure (approximately 2.4 mm Hg) 3
- Heart rate may increase by approximately 9 bpm 3
Psychiatric Monitoring
- Monitor closely for suicidal ideation, especially in children and adolescents during the first few months of treatment 2
- Watch for clinical worsening or unusual changes in behavior
- Assess for emergence of irritability, anxiety, or mood changes
Efficacy Expectations
- Approximately 50% of non-responders to stimulants will respond to atomoxetine 1
- Approximately 75% of responders to stimulants will also respond to atomoxetine 1
- Full therapeutic effects may take 6-12 weeks to develop, unlike the rapid onset of stimulants 2
- Atomoxetine provides "around-the-clock" effects rather than time-limited coverage 2
Common Side Effects to Anticipate
- Most common: nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence 2, 3
- Most side effects are mild to moderate in severity
- Somnolence is more common with atomoxetine compared to stimulants 4
- Insomnia is less common with atomoxetine compared to stimulants 4
Special Considerations
Metabolism Considerations
- Atomoxetine is metabolized through CYP2D6
- Approximately 7% of the population are poor metabolizers, which may lead to higher plasma levels and more side effects 2
- Avoid co-administration with CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) which can elevate atomoxetine levels 2
Advantages of Atomoxetine Over Stimulants
- Not classified as a controlled substance - beneficial for patients with substance use concerns 4
- Effective for patients with comorbid anxiety, tics, or sleep disturbances 4
- Lower risk of abuse or misuse 4
- No rebound effects if doses are missed 1
Potential Pitfalls and How to Avoid Them
Premature efficacy assessment: Avoid concluding lack of efficacy before 6-8 weeks of atomoxetine treatment 1
Inadequate dosing: Ensure proper weight-based dosing (target: 1.2-1.4 mg/kg/day) 2
Poor tolerability during transition: Consider divided doses of atomoxetine initially to minimize side effects 1
Withdrawal symptoms from Adderall: The cross-tapering approach helps minimize this risk 3
Overlooking cardiovascular effects: While generally modest, monitor blood pressure and heart rate regularly 3
If atomoxetine monotherapy proves insufficient after an adequate trial, some evidence suggests that combination therapy with stimulants may benefit certain treatment-resistant patients, though this is an off-label approach requiring careful consideration 5.