What is the recommended cross-taper protocol from Wellbutrin (bupropion) to atomoxetine for a patient with Attention Deficit Hyperactivity Disorder (ADHD)?

Cross-Taper from Wellbutrin to Atomoxetine for ADHD

Use a 2-week cross-taper protocol: start atomoxetine at 0.5 mg/kg/day while continuing full-dose bupropion for week 1, then increase atomoxetine to 1.2 mg/kg/day while reducing bupropion to half-dose for week 2, followed by atomoxetine monotherapy. 1

Evidence-Based Cross-Taper Protocol

The most direct evidence for switching between these medications comes from a study that successfully transitioned patients from stimulants to atomoxetine using a stepwise approach 1. While this study focused on stimulants, the same pharmacodynamic principles apply when switching from bupropion, as both require time to establish therapeutic levels.

Week 1: Initiation Phase

• Continue current bupropion dose (whether SR 100-150 mg BID or XL 150-300 mg daily) 2, 3
• Start atomoxetine at 40 mg orally once daily (approximately 0.5 mg/kg/day) 2, 1
• This overlap prevents symptom worsening during the transition period 1

Week 2: Transition Phase

• Increase atomoxetine to 60-80 mg daily (approximately 1.2 mg/kg/day) 2, 1
• Reduce bupropion to half the current dose 1
• Monitor for overlapping side effects, particularly cardiovascular changes 2

Week 3 Onward: Monotherapy Phase

• Discontinue bupropion completely (can be stopped abruptly without tapering) 3
• Continue atomoxetine at 60-80 mg daily, with option to titrate every 7-14 days up to maximum of 100 mg/day or 1.4 mg/kg/day, whichever is less 2, 4

Critical Monitoring During Cross-Taper

Cardiovascular Parameters

• Monitor heart rate and blood pressure at each visit, as both medications can increase these parameters 2, 4
• Expect mild increases in heart rate (mean 9.2 bpm) and blood pressure (mean 2.4 mm Hg systolic and diastolic) during atomoxetine initiation 1
• Obtain baseline cardiac history including family history of sudden death, arrhythmias, or structural heart disease before starting 4

Neuropsychiatric Effects

• Watch for mood changes, agitation, irritability, or suicidal ideation, particularly in the first 24-48 hours after dose changes 2, 4
• Atomoxetine carries an FDA black box warning for suicidal ideation, though this risk is uncommon 4, 5
• Both medications can affect mood, so monitor closely during the overlap period 2

Common Side Effects

• Somnolence and fatigue are more common with atomoxetine than bupropion 5, 1
• Initial gastrointestinal symptoms (nausea, abdominal pain) may occur with atomoxetine, especially if dose escalation is too rapid 4, 1
• Decreased appetite can occur with both medications 4, 1
• Insomnia may persist during transition as both medications can cause sleep disturbances 2

Important Clinical Considerations

Efficacy Timeline

• Allow 6-8 weeks on atomoxetine monotherapy before evaluating full therapeutic response 6
• Atomoxetine requires daily dosing to build and maintain therapeutic levels, unlike stimulants which work immediately 3
• Approximately 50% of patients who don't respond fully to one ADHD medication will respond to atomoxetine 6

Safety of Co-Administration

• The combination of bupropion and atomoxetine can be safely administered during the cross-taper period with appropriate monitoring 2
• No specific drug-drug interactions are documented between these medications 2
• However, both affect cardiovascular parameters, so cumulative effects require monitoring 2, 1

Contraindications and Cautions

• Bupropion is contraindicated in patients with seizure disorders, so if this was the reason for switching, ensure complete discontinuation 2
• Atomoxetine requires dose adjustment in hepatic insufficiency and in patients taking CYP2D6 inhibitors 5
• Consider slower titration in patients who are CYP2D6 poor metabolizers, as they have greater atomoxetine exposure 5

Common Pitfalls to Avoid

• Do not abruptly stop bupropion before starting atomoxetine, as this creates a treatment gap that may worsen ADHD symptoms 1
• Do not rush atomoxetine titration, as rapid dose increases cause more gastrointestinal side effects and somnolence 4, 1
• Do not evaluate atomoxetine efficacy too early, as it requires 6-8 weeks to reach full therapeutic effect 6
• Do not forget cardiovascular monitoring, as both medications can increase heart rate and blood pressure, with potentially additive effects during overlap 2, 1