How should I taper bupropion (Wellbutrin) 300 mg daily in an adult?

How to Properly Wean Off Wellbutrin 300mg

When discontinuing bupropion 300 mg daily, reduce the dose to 150 mg once daily for at least one week before complete discontinuation. 1

FDA-Approved Tapering Protocol

The FDA label provides explicit guidance for discontinuing bupropion extended-release formulations:

• For patients on 300 mg once daily, decrease to 150 mg once daily before stopping the medication entirely. 1
• This represents the only FDA-specified tapering regimen for bupropion discontinuation. 1

Duration of Taper and Clinical Monitoring

The minimum duration of the 150 mg step should be at least one week, though the FDA label does not specify an exact timeframe beyond stating to "taper the dose." 1

• Monitor patients within 1–2 weeks of any dosing change to assess for withdrawal symptoms, mood changes, or suicidal ideation—particularly in patients younger than 24 years. 2
• The risk of suicide attempts remains elevated during treatment transitions, especially in the first 1–2 months of any antidepressant change. 2

Evidence for Withdrawal Symptoms

Although bupropion is often described as having minimal discontinuation syndrome compared to SSRIs, withdrawal symptoms can occur:

• Case reports document irritability, anxiety, insomnia, headache, and generalized aches following abrupt bupropion discontinuation. 3
• These symptoms mirror nicotine withdrawal and may be confused with relapse of depression. 3
• A slow taper is recommended to minimize withdrawal symptoms, with patient education about the benefits of gradual discontinuation. 3

Formulation-Specific Considerations

Close monitoring is essential when switching between bupropion formulations (brand to generic, SR to XL) due to historical bioequivalence issues that may lead to loss of antidepressant effect. 4

• If you are discontinuing Wellbutrin SR (150 mg twice daily), the equivalent taper would be to reduce to 150 mg once daily before stopping. 4
• For Wellbutrin XL 300 mg once daily, follow the FDA protocol: reduce to 150 mg once daily, then discontinue. 1

Practical Tapering Algorithm

Standard taper (most patients):

1. Week 1–7+: Reduce from 300 mg daily to 150 mg daily 1
2. Week 8+: Discontinue completely after at least one week at 150 mg 1
3. Monitor closely for withdrawal symptoms, mood changes, or suicidal ideation during weeks 1–2 of each dose change 2

Slower taper (high-risk patients):

For patients with a history of severe withdrawal from other antidepressants, multiple prior depressive episodes, or significant anxiety about discontinuation:

1. Weeks 1–2: Reduce from 300 mg daily to 150 mg daily 1
2. Weeks 3–4: Continue 150 mg daily with close monitoring 2
3. Weeks 5–6: Consider reducing to 150 mg every other day (this dosing interval is established as safe in hepatic impairment) 4
4. Week 7+: Discontinue completely 1

Critical Safety Screening Before Discontinuation

Verify adequate treatment duration before stopping:

• First episode of depression requires at least 4–9 months of treatment before discontinuation should be considered. 2
• Recurrent depression (≥2 episodes) requires ≥1 year of maintenance therapy, as relapse risk reaches 70% after two episodes and 90% after three episodes. 2
• Do not discontinue prematurely unless significant adverse effects occur. 4

Management of Withdrawal Symptoms During Taper

If withdrawal symptoms emerge:

• Slow the taper rate by extending the interval between dose reductions from one week to 2–4 weeks. 5
• Consider adjunctive medications such as trazodone 100 mg nightly for insomnia and anxiety. 5
• Increase monitoring frequency with follow-up visits or phone calls every 1–2 weeks. 5

Common Pitfalls to Avoid

• Do not abruptly discontinue bupropion 300 mg without tapering—case reports document significant withdrawal symptoms with abrupt cessation. 3
• Do not assume generic formulations are equivalent—historical bioequivalence issues mean any formulation change requires close monitoring. 4
• Do not discontinue before adequate treatment duration (minimum 4 months for first episode) unless adverse effects necessitate stopping. 4
• Do not skip intensive monitoring during the first 1–2 weeks after dose reduction, as this period carries the highest risk for mood destabilization. 2

Special Populations

Older adults or patients with renal/hepatic impairment:

• Consider even slower tapers due to increased risk of adverse effects during withdrawal. 5
• For patients with moderate to severe hepatic impairment already on reduced dosing, the taper may need to extend over several weeks. 4