Weaning Off Wellbutrin XL (Bupropion)
For patients on Wellbutrin XL 300 mg daily, taper to 150 mg once daily before discontinuation; patients on lower doses may discontinue without tapering, though gradual reduction over 1-2 weeks minimizes potential withdrawal symptoms. 1
FDA-Approved Tapering Protocol
The FDA label provides explicit guidance for discontinuing Wellbutrin XL:
- Patients taking 300 mg daily: Decrease to 150 mg once daily prior to complete discontinuation 1
- Duration at reduced dose: The FDA label does not specify a minimum duration at 150 mg, but maintaining this dose for at least 1-2 weeks before stopping is prudent based on general antidepressant discontinuation principles
- Patients on 150 mg daily: The FDA label does not mandate tapering for this dose, though gradual reduction may still be beneficial 1
Clinical Context and Withdrawal Risk
While bupropion is not typically associated with severe discontinuation syndromes like SSRIs, withdrawal symptoms can occur:
- Documented withdrawal symptoms: Irritable mood, anxiety, sleeplessness, headache, and generalized aches and pains have been reported with abrupt bupropion discontinuation 2
- Risk factors: Longer duration of treatment and higher doses increase withdrawal risk, though specific thresholds are not well-established for bupropion 2
Practical Tapering Approach
For 300 mg XL formulation:
- Week 1-2: Reduce to 150 mg once daily in the morning 1
- Week 3: Discontinue completely, or consider extending 150 mg for another 1-2 weeks if patient has been on treatment for >6 months
For 150 mg XL formulation:
- May discontinue directly, or
- Consider splitting to every-other-day dosing for 1-2 weeks if patient has been on treatment for extended periods (>6 months) or has history of withdrawal symptoms with other medications
Important Caveats
- Timing considerations: Continue morning administration during taper to maintain the established routine and minimize insomnia risk 3
- Do not split tablets: Wellbutrin XL must be swallowed whole and cannot be crushed, divided, or chewed, which limits flexible tapering options 1
- Monitor for symptom recurrence: The primary concern during discontinuation is return of depressive symptoms rather than withdrawal symptoms; assess mood, energy, and functioning throughout the taper 1
- Patient education: Inform patients about potential mild withdrawal symptoms and the importance of not abruptly stopping medication 2
Special Populations
- Hepatic impairment: Patients with moderate to severe hepatic impairment already on reduced dosing (150 mg every other day) may discontinue without further tapering 1
- Renal impairment: Patients with reduced dosing due to renal impairment may discontinue their current reduced dose without additional tapering 1
The key principle is that bupropion discontinuation is generally straightforward compared to other antidepressants, with the main FDA-mandated step being reduction from 300 mg to 150 mg before complete cessation. 1