What is the recommended protocol for tapering off Wellbutrin (bupropion) and starting Venlafaxine (venlafaxine)?

Switching from Wellbutrin (Bupropion) to Venlafaxine

Taper bupropion by reducing the dose by 10% of the most recent dose every 5-7 days until discontinuation, then initiate venlafaxine at 37.5 mg once or twice daily after a washout period is not required since these medications do not interact significantly. 1

Bupropion Discontinuation Protocol

Tapering Strategy

• Reduce the dose by increments of the initial dose every 5-7 days until complete discontinuation 1
• For example, if taking 150 mg twice daily (300 mg total):
  • Week 1: Reduce to 150 mg once daily
  • Week 2: Reduce to 75 mg once daily (if available) or 150 mg every other day
  • Week 3: Discontinue 1
• The taper should take 10-14 days minimum to limit withdrawal symptoms 1

Managing Withdrawal Symptoms

• Bupropion withdrawal is generally mild compared to serotonergic antidepressants, but patients may experience fatigue, mood changes, or irritability 2
• If withdrawal symptoms occur, return to the previous well-tolerated dose and slow the taper rate 2
• Consider symptomatic treatment with acetaminophen or NSAIDs for any muscle aches 1

Initiating Venlafaxine

Starting Dose

• Begin venlafaxine at 37.5 mg once or twice daily 1
• No washout period is required between bupropion and venlafaxine as they work through different mechanisms (bupropion affects dopamine/norepinephrine via different pathways than venlafaxine's serotonin/norepinephrine reuptake inhibition) 1

Titration Schedule

• Increase by 75 mg each week as tolerated 1
• Target therapeutic dose is typically 150-225 mg/day 1
• Maximum dose is 225 mg/day 1
• Allow 2-4 weeks to reach an efficacious dosage 1

Monitoring During Titration

• Monitor blood pressure, as venlafaxine can cause dose-dependent increases 1
• Prescribe with caution in patients with cardiac disease due to potential cardiac conduction abnormalities 1
• Assess for common side effects including nausea, sweating, tremors, nervousness, insomnia or somnolence, dizziness, and gastrointestinal disturbances 1

Cross-Titration Approach (Alternative Strategy)

You can overlap the medications during the transition rather than completing the bupropion taper first:

• Start venlafaxine at 37.5 mg daily while maintaining current bupropion dose 1
• After 3-7 days, begin reducing bupropion by 10% increments every 5-7 days 1
• Simultaneously increase venlafaxine by 37.5-75 mg weekly as tolerated 1
• This approach may minimize any gap in antidepressant coverage and reduce withdrawal risk 2

Critical Pitfalls to Avoid

• Never abruptly discontinue bupropion, even though its withdrawal syndrome is milder than SSRIs/SNRIs - this can still cause significant distress and missed work days 2
• Do not rush the venlafaxine titration - it requires 2-4 weeks minimum to reach therapeutic doses, and faster titration increases side effects 1
• Remember that venlafaxine itself requires careful tapering when eventually discontinued due to its short half-life and well-documented withdrawal syndrome 1, 2
• Do not abandon the patient during this transition - close monitoring and support are essential, with clinician availability to manage symptoms and address fears 1

Patient Education

• Inform patients that withdrawal symptoms from bupropion, if they occur, are typically mild and self-limiting 2
• Explain that venlafaxine may take 4-6 weeks at therapeutic doses to show full antidepressant effects 1
• Reassure patients that symptoms are usually transient and can be managed by adjusting the taper rate 2
• Advise taking the second dose of venlafaxine before 3 p.m. if using twice-daily dosing to minimize insomnia risk 1