Tapering Wellbutrin 300 mg for Depression
For a patient on Wellbutrin (bupropion) 300 mg daily for depression, reduce to 150 mg once daily for 1-2 weeks before complete discontinuation. 1
FDA-Approved Tapering Protocol
The FDA label for bupropion extended-release explicitly states: "When discontinuing treatment in patients treated with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation." 1
This is the only FDA-specified tapering instruction for bupropion and should be followed as the standard approach. 1
Recommended Timeline
Week 1-2: Reduce from 300 mg to 150 mg once daily in the morning 2, 1
Week 3: Discontinue completely after tolerating 150 mg for 1-2 weeks 2
The 150 mg dose represents a sub-therapeutic maintenance level for depression (standard therapeutic dose is 300 mg), making it an appropriate intermediate step before complete cessation. 2
Why Bupropion Requires Less Aggressive Tapering
Unlike SSRIs, bupropion's mechanism of dopamine/norepinephrine reuptake inhibition produces less severe withdrawal syndromes than serotonergic agents. 2 The standard NCCN dosing demonstrates that bupropion tolerates relatively rapid dose transitions—it can be initiated at 150 mg and increased to 300 mg after just 3 days, suggesting forgiving pharmacokinetics. 2
General antidepressant discontinuation guidelines recommend 10-14 days for tapering, and bupropion's unique mechanism makes it less prone to withdrawal syndromes compared to SSRIs. 2
Monitoring for Withdrawal Symptoms
While uncommon, watch for:
These symptoms have been reported with abrupt bupropion discontinuation, reinforcing the importance of gradual tapering. 3
Special Consideration: Depression Symptom Rebound
Highly nicotine-dependent smokers treated with bupropion experience decreased depressive symptoms during active treatment but may experience rebound depression when bupropion is discontinued. 4 While this study focused on smoking cessation, the principle applies to depression treatment—monitor closely for mood deterioration after discontinuation. 4
If Withdrawal Symptoms Emerge
For patients experiencing withdrawal symptoms during the standard taper, consider:
- Extending the 150 mg phase to 4-6 weeks before discontinuation 2
- Alternating 150 mg daily with 150 mg every other day for 1-2 weeks before complete cessation 2
Critical Safety Points
- Never stop abruptly from 300 mg—always step down to 150 mg first 1
- Educate patients about potential withdrawal symptoms and the benefits of compliance 3
- Reassess the need for continued antidepressant treatment before discontinuation 1
- If depression symptoms worsen during tapering, consider maintaining treatment rather than forcing discontinuation 1
Comparison to Other Antidepressants
SSRIs require much more gradual, hyperbolic tapering down to doses far below therapeutic minimums to minimize withdrawal. 5 Bupropion's simpler two-step taper (300→150→0) over 2-3 weeks contrasts sharply with SSRI tapers that may require months and exponential dose reductions. 5, 6