What is the recommended titration for atomoxetine (Attention Deficit Hyperactivity Disorder medication) and bupropion (antidepressant)?

Titration Protocols for Atomoxetine and Bupropion

Atomoxetine Titration

For atomoxetine, start with 40 mg once daily in the morning, then increase to 60 mg after 7-14 days, followed by 80 mg after another 7-14 days if needed, with a maximum dose of 100 mg/day (or 1.4 mg/kg/day, whichever is less). 1

Starting Dose

• Begin with 40 mg orally once daily 1, 2
• Can be administered as a single morning dose or split into two equal doses (morning and evening) to reduce adverse effects 1

Titration Schedule

• Adjust dose every 7-14 days based on clinical response and tolerability 1, 2
• Increase to 60 mg daily after the first 7-14 days 1
• Increase to 80 mg daily (target dose) after another 7-14 days if needed 1
• Maximum dose: 100 mg/day or 1.4 mg/kg/day, whichever is less 1, 2

Important Timing Considerations

• Therapeutic effects typically require 6-12 weeks to fully manifest, which is significantly longer than stimulants 1
• This delayed onset means patience is essential during titration—do not increase doses too rapidly expecting immediate results 1

Special Populations

• CYP2D6 poor metabolizers (approximately 7% of population) require lower doses due to increased drug exposure 2, 3
• Patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) also require dose adjustment 2, 3

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Bupropion Titration

For bupropion, the titration depends on the formulation: SR formulation starts at 100-150 mg once daily, increasing to 100-150 mg twice daily; XL formulation starts at 150 mg once daily, increasing to 300 mg once daily, with a maximum of 450 mg/day. 1

Sustained-Release (SR) Formulation

• Starting dose: 100-150 mg once daily 1
• Maintenance dose: 100-150 mg twice daily 1
• Increase dose by 37.5 mg every 3 days as tolerated 1

Extended-Release (XL) Formulation

• Starting dose: 150 mg once daily 1
• Maintenance dose: 150-300 mg once daily 1
• Maximum dose: 450 mg per day 1

Timing Considerations

• Give second dose before 3 PM to minimize insomnia risk 1
• Bupropion is activating and may provide rapid improvement in energy levels 1
• Therapeutic effects for ADHD typically require 2-4 weeks to assess adequacy 4

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Critical Safety Monitoring During Titration

For Atomoxetine

• Monitor for suicidality closely, especially during the first few months and at dose changes 2
• Assess cardiovascular parameters: heart rate and blood pressure increases are common 2, 3
• Monitor growth parameters in pediatric patients (height and weight) 2
• Common adverse effects include nausea, vomiting, fatigue, decreased appetite, and somnolence 2, 3

For Bupropion

• Contraindicated in patients with seizure disorders or conditions that increase seizure risk 1
• Monitor for activation, agitation, and insomnia 1
• Assess for cardiovascular effects, though generally well-tolerated 4

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Practical Titration Algorithm

1. Week 0-1: Start atomoxetine 40 mg daily OR bupropion SR 100-150 mg daily (or XL 150 mg daily)
2. Week 1-2: Continue initial dose, assess tolerability
3. Week 2-3: Increase atomoxetine to 60 mg daily OR bupropion SR to twice daily dosing (or XL to 300 mg daily)
4. Week 3-4: Continue and assess response
5. Week 4-6: If needed, increase atomoxetine to 80 mg daily (maximum 100 mg)
6. Week 6-12: Continue monitoring—remember atomoxetine requires 6-12 weeks for full therapeutic effect 1

Key pitfall to avoid: Do not abandon atomoxetine prematurely—its delayed onset of 6-12 weeks means inadequate trial duration is a common reason for perceived treatment failure 1. For bupropion, ensure adequate trial of at least 4 weeks before declaring inefficacy 4.