What is the recommended tapering schedule for a patient being discontinued from Wellbutrin (bupropion) 450mg XL to 150mg XL?

Tapering Wellbutrin from 450mg XL to 150mg XL

For patients tapering bupropion from 450mg XL to 150mg XL, reduce directly to 300mg XL for 1-2 weeks, then to 150mg XL for 4-6 weeks before considering complete discontinuation if needed. 1

Recommended Tapering Protocol

Initial Dose Reduction

• Reduce from 450mg XL directly to 300mg XL and maintain this dose for 1-2 weeks 2
• This represents a 33% reduction from the starting dose, which is consistent with general antidepressant tapering principles 3

Second Reduction to Target Dose

• After tolerating 300mg XL for 1-2 weeks, reduce to 150mg XL 2, 1
• Maintain 150mg XL for 4-6 weeks before any further reduction or discontinuation 1
• This extended period at 150mg allows assessment of withdrawal symptoms and stabilization

If Planning Complete Discontinuation

• After the 4-6 week period at 150mg XL, consider alternating 150mg daily with 150mg every other day for 1-2 weeks before stopping completely 1
• This final step provides a gentler transition off the medication entirely

Why Bupropion Requires Less Aggressive Tapering

• Bupropion's mechanism of dopamine/norepinephrine reuptake inhibition produces less severe withdrawal symptoms compared to serotonergic antidepressants (SSRIs/SNRIs) 1
• The standard NCCN dosing for smoking cessation demonstrates that bupropion can be initiated at 150mg daily and increased to 300mg daily after just 3 days, suggesting the medication has relatively forgiving dose transitions 2
• Unlike SSRIs which require hyperbolic tapering to very low doses, bupropion can typically be reduced in larger increments 4

Monitoring for Withdrawal Symptoms

Common Withdrawal Symptoms to Watch For

• Somatic symptoms: dizziness, light-headedness, fatigue, lethargy, myalgia, flu-like symptoms, sleep disturbances 3
• Psychological symptoms: anxiety, agitation, crying spells, irritability 3
• These symptoms typically emerge within days of dose reduction and are generally mild and self-limiting 3

If Withdrawal Symptoms Become Problematic

• Return to the previous well-tolerated dose temporarily 5
• Extend the time between dose reductions (e.g., stay at 300mg for 3-4 weeks instead of 1-2 weeks) 5
• Consider even slower tapering by extending the 150mg phase to 8-12 weeks 1
• Time the final discontinuation when the patient has fewer life stressors 5

Critical Pitfalls to Avoid

• Do not confuse withdrawal symptoms with relapse of depression - withdrawal symptoms typically occur within days of dose reduction and include physical symptoms like dizziness, while relapse develops more gradually over weeks 3, 6
• Do not set arbitrary time limits for completing the taper - individualize based on patient response and tolerance 5
• Do not abruptly discontinue - even though bupropion has milder withdrawal than SSRIs, gradual tapering minimizes distressing symptoms that could lead to missed work and decreased productivity 3
• Reassure patients that mild withdrawal symptoms are usually transient and self-limiting 3

Special Considerations

• The maximum therapeutic dose of 300mg daily for depression means that 150mg represents a sub-therapeutic maintenance dose, making it an appropriate stopping point if continuing treatment 2
• For patients using bupropion for smoking cessation, the standard treatment duration is 7-12 weeks, suggesting that extended use at lower doses is well-tolerated 2
• Monitor for neuropsychiatric symptoms (depression, suicidal ideation) during tapering, though these are uncommon 2

Timeline Summary

• Week 1-2: 300mg XL daily
• Week 3-8 (or longer): 150mg XL daily
• Week 9-10 (if discontinuing completely): Alternate 150mg daily with every other day
• Week 11+: Complete discontinuation if appropriate

This approach balances the need to prevent withdrawal symptoms while avoiding unnecessary complexity, recognizing that bupropion's pharmacology makes it more forgiving than serotonergic antidepressants 1, 3.