Wellbutrin Discontinuation Protocol
For patients on bupropion XL 300 mg daily, reduce to 150 mg once daily before complete discontinuation; this gradual taper minimizes withdrawal symptoms and is the FDA-recommended approach. 1
FDA-Approved Tapering Strategy
The FDA label explicitly states that when discontinuing bupropion extended-release tablets at 300 mg per day, decrease the dose to 150 mg once daily before stopping the medication entirely. 1 This represents the highest-quality guidance available, as it comes directly from the manufacturer's approved prescribing information.
- The 150 mg step-down dose should be maintained for a reasonable period (typically 1-2 weeks based on general antidepressant tapering principles) before complete cessation 1, 2
- Bupropion XL should be swallowed whole in the morning and may be taken with or without food 1
Formulation-Specific Considerations
Different bupropion formulations require different tapering approaches:
- Bupropion SR (sustained-release): When tapering from 300 mg daily, reduce to 150 mg once daily before discontinuation 3
- Bupropion XL (extended-release): Follow the FDA protocol of 300 mg to 150 mg to discontinuation 1
- SR formulations require twice-daily dosing adjustments, while XL is dosed once daily 3
Special Populations Requiring Modified Tapering
Older adults need slower, more gradual tapers:
- Consider smaller dose reductions such as 37.5 mg decrements in elderly patients due to increased risk of adverse reactions 3
- Patients with hepatic impairment (moderate to severe) should already be on reduced dosing (maximum 150 mg every other day), making discontinuation simpler 1
- Those with renal impairment may require extended tapering periods given altered drug clearance 1
Critical Monitoring During Discontinuation
Monitor specific populations and parameters closely:
- Patients under 24 years: Watch for changes in mood, behavior, or emergence of suicidal ideation during the taper 3
- All patients: Monitor blood pressure throughout the discontinuation process, as bupropion affects cardiovascular parameters 3
- Combination therapy patients: If bupropion is part of naltrexone-bupropion for weight management, discontinue before any procedure requiring opioid analgesia 3
Withdrawal Symptom Recognition
Bupropion withdrawal symptoms, though less common than with SSRIs, can occur:
- Documented symptoms include irritable mood, anxiety, sleeplessness, headache, and generalized aches and pains following abrupt discontinuation 4
- These symptoms are distinct from the more severe discontinuation syndromes seen with serotonergic antidepressants 2
- If withdrawal symptoms emerge, reinstate the previous dose and taper more slowly 2
Common Pitfalls to Avoid
Do not make these errors:
- Never abruptly discontinue without attempting a taper, even though bupropion has a lower risk of discontinuation syndrome than SSRIs 4, 2
- Do not ignore formulation differences: SR requires twice-daily considerations while XL is once-daily 3
- Avoid rapid tapers in elderly patients who metabolize medications more slowly 3
- Do not confuse bupropion tapering with SSRI tapering protocols: Bupropion's norepinephrine-dopamine mechanism differs substantially from serotonergic agents 4
When to Extend the Taper
Consider a slower, more gradual approach if:
- The patient is elderly or has multiple comorbidities 3
- Previous antidepressant discontinuation attempts resulted in significant symptoms 2
- The patient has been on bupropion for an extended period (years rather than months) 2
- Withdrawal symptoms emerge during the initial dose reduction 4, 2
Patient Education Points
Inform patients that:
- The taper process typically takes 1-2 weeks minimum for the standard 300 mg to 150 mg to zero protocol 1
- Withdrawal symptoms, if they occur, are generally mild compared to other antidepressants 4
- They should report any mood changes, anxiety, or physical symptoms immediately 3, 4
- Compliance with the tapering schedule reduces the risk of withdrawal symptoms 4