How do you safely discontinue Wellbutrin (bupropion)?

Discontinuing Wellbutrin (Bupropion)

For patients on 300 mg daily, taper to 150 mg once daily before complete discontinuation; for those on 150 mg daily, discontinuation can proceed without further tapering. 1

FDA-Approved Tapering Protocol

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

• Patients taking 300 mg/day: Decrease to 150 mg once daily prior to complete discontinuation 1
• Patients taking 150 mg/day or less: Can discontinue without further dose reduction 1
• Timing for seasonal affective disorder: Taper and discontinue in early spring after winter season treatment 1

This represents the most authoritative guidance available, as it comes directly from the FDA-approved prescribing information.

Formulation-Specific Considerations

Sustained-Release (SR) formulation: If tapering from 300 mg/day (150 mg twice daily), reduce to 150 mg once daily before stopping 2

Extended-Release (XL) formulation: Follow the same principle—step down from 300 mg to 150 mg once daily before complete cessation 1

The tapering approach minimizes potential discontinuation effects, though bupropion is generally associated with fewer withdrawal symptoms compared to other antidepressants due to its unique mechanism of action (dopamine-norepinephrine reuptake inhibition rather than serotonergic effects). 3, 4

Duration of Taper

While the FDA label does not specify an exact duration for the 150 mg maintenance phase before stopping, clinical practice typically involves:

• Maintain 150 mg daily for 1-2 weeks before complete discontinuation to allow gradual adjustment 1
• For patients with history of severe depression or multiple relapses: Consider extending the 150 mg phase to 2-4 weeks 5

Monitoring During Discontinuation

Watch for these specific symptoms during and after tapering:

• Mood changes: Increased sadness, irritability, or anxiety that may signal relapse rather than withdrawal 5
• Physical symptoms: Headache, insomnia, or fatigue (though these are less common with bupropion than with serotonergic antidepressants) 6, 4
• Return of original symptoms: Monitor for re-emergence of depression or other indication for which bupropion was prescribed 1

Critical Timing Considerations

Do not abruptly discontinue bupropion at higher doses (300 mg or above) without tapering, as this bypasses the FDA-recommended safety protocol 1

For smoking cessation: Treatment typically lasts 7-12 weeks, after which discontinuation follows the same tapering protocol if the patient was on 300 mg daily 2

Special Population Adjustments

Patients with hepatic impairment: Those on reduced doses (150 mg every other day for severe impairment) can typically stop without further taper 1

Patients with renal impairment: Those already on reduced dosing may discontinue their current dose without additional tapering 1

Older adults: Follow standard tapering protocol, though these patients may already be on lower maintenance doses 2, 7

Common Pitfalls to Avoid

Do not confuse bupropion discontinuation with SSRI discontinuation: Bupropion has a different mechanism and generally causes fewer withdrawal symptoms than serotonergic antidepressants 3, 4

Do not use prolonged, complex tapering schedules: The evidence supports a simple one-step reduction from 300 mg to 150 mg, not gradual decrements over many weeks 1

Do not stop abruptly in patients with bipolar disorder: These patients require careful monitoring during any medication changes due to risk of mood destabilization 7

When Psychological Support May Be Needed

For patients discontinuing after long-term use (6+ months) for recurrent depression, consider:

• Preventive cognitive therapy or mindfulness-based cognitive therapy during the discontinuation process may help prevent relapse, though evidence is of low certainty 5
• Close follow-up: Schedule visits at 2 weeks and 4-6 weeks post-discontinuation to assess for relapse 5

The evidence for psychological support during antidepressant discontinuation is limited and of low quality, but may be reasonable for high-risk patients with recurrent depression. 5