How to discontinue Wellbutrin (bupropion) in a patient with a history of suicidal ideation taking Wellbutrin (bupropion) 300mg XL, trazodone 100mg QHS, and duloxetine 60mg daily, while continuing trazodone and duloxetine?

Discontinuing Wellbutrin (Bupropion) While Continuing Trazodone and Duloxetine

Direct Tapering Protocol

For a patient on Wellbutrin 300mg XL, taper by decreasing to 150mg once daily for at least one week before complete discontinuation. 1

The FDA-approved prescribing information explicitly states that when discontinuing bupropion hydrochloride extended-release tablets (XL) 300mg once daily, you should decrease the dose to 150mg once daily prior to discontinuation. 1 This gradual reduction minimizes potential withdrawal symptoms, though bupropion has a relatively favorable discontinuation profile compared to SSRIs. 2

Critical Monitoring During Discontinuation

Suicidal Ideation Surveillance

• Monitor closely for increased suicidal ideation, particularly since this patient has a documented history of suicidal thoughts. 2
• The risk is especially elevated in patients under 24 years old, though vigilance is warranted at any age given the patient's psychiatric history. 2
• Recent evidence from the VAST-D trial demonstrates that approximately 1 in 5 patients experience emergent or worsening suicidal ideation during antidepressant treatment changes, necessitating vigilance through the entire transition period. 3

Energy and Mood Changes

• Watch for fatigue or decreased energy levels, as bupropion has activating properties and patients may experience withdrawal-related lethargy. 2
• The patient may notice reduced motivation or increased apathy as the dopaminergic/noradrenergic effects of bupropion diminish. 2
• Monitor for return of depressive symptoms over several weeks following complete discontinuation, as mood changes may not manifest immediately. 4

Timing Considerations

Complete the taper over a minimum of 1-2 weeks total. 1, 2

• Week 1: Reduce from 300mg XL to 150mg XL once daily in the morning 1
• Week 2 onward: Discontinue completely after at least 7 days at 150mg 1

The Mayo Clinic notes that while a slower taper is generally safer, unnecessarily prolonged tapers can become a source of patient anxiety. 2 The FDA-recommended one-week minimum at the reduced dose balances safety with practicality. 1

Why Continue Duloxetine and Trazodone

Maintaining duloxetine 60mg daily and trazodone 100mg QHS provides continued antidepressant coverage and sleep support during the bupropion discontinuation. 5

• Duloxetine addresses serotonergic and noradrenergic pathways, providing robust antidepressant effects that can compensate for bupropion withdrawal. 5
• Trazodone continues to manage sleep disturbances and provides additional serotonergic activity. 4
• Evidence suggests that switching between antidepressant classes (in this case, removing the dopaminergic agent while maintaining serotonergic coverage) is an effective strategy in treatment-resistant depression. 5

Drug Interaction Considerations

Be aware that the combination of duloxetine and bupropion involves CYP2D6 inhibition by both agents, which may have contributed to adverse effects. 6

• Both duloxetine and bupropion inhibit cytochrome P450 2D6, potentially leading to elevated hydroxybupropion levels and increased dopaminergic activity. 6
• In elderly patients, this combination has been associated with delirium, though your patient's age is not specified. 6
• Discontinuing bupropion eliminates this interaction risk while maintaining duloxetine's therapeutic benefits. 6

Post-Discontinuation Follow-Up

Schedule follow-up within 1-2 weeks after complete bupropion discontinuation to assess for withdrawal symptoms and mood stability. 2

• Monitor for depressive symptom recurrence over the subsequent 4-8 weeks, as mood changes may emerge gradually. 4
• Assess whether the remaining medication regimen (duloxetine + trazodone) provides adequate symptom control. 5
• If depressive symptoms worsen after bupropion discontinuation, consider that the patient may have been benefiting from the combination therapy, and alternative augmentation strategies may be needed. 7

Common Pitfalls to Avoid

• Do not discontinue bupropion abruptly from 300mg without the intermediate 150mg step. 1 The FDA label specifically requires this taper for the 300mg dose.
• Do not assume the patient will be stable immediately after stopping bupropion. 4 Extended monitoring over weeks to months may be required to identify delayed symptom return.
• Do not neglect suicide risk assessment during the transition period. 3 Recent evidence shows significant rates of emergent suicidal ideation during antidepressant treatment changes, even when switching or discontinuing rather than initiating therapy.