If a patient is not experiencing psychotic features, should I discontinue risperidone and add bupropion (Wellbutrin) to sertraline (Zoloft)?

Discontinuing Risperidone and Adding Bupropion to Sertraline

Yes, you should discontinue risperidone if the patient is not experiencing psychotic features, as antipsychotics are not indicated for behavioral symptoms without psychosis. 1

Rationale for Discontinuing Risperidone

Guideline consensus clearly states that antipsychotics should only be used for behavioral symptoms when psychotic features (hallucinations, delusions causing distress) are present. 1 The American Geriatrics Society consensus panel specifically found that they did not reach consensus supporting the use of antipsychotics for behavioral symptoms in the absence of psychotic features, even despite some positive trial data. 1

• Pharmacological treatments used only for behavioral symptoms should be evaluated for tapering or discontinuation within 6 months after symptoms stabilize, with attempts at discontinuation every 6 months thereafter. 1

• Continuing risperidone without psychotic features exposes the patient to unnecessary risks including extrapyramidal symptoms, metabolic effects, and potential for increased mortality in elderly patients with dementia. 2

Adding Bupropion to Sertraline: Cross-Taper Approach

If augmenting sertraline with bupropion for depression, use a cross-taper method while simultaneously discontinuing risperidone. 3

Specific Dosing Protocol

• Start bupropion SR at 150 mg once daily while maintaining current sertraline dose. 3

• After 3 days, increase bupropion to 150 mg twice daily (300 mg total daily dose). 3

• Take the second bupropion dose before 3 PM to minimize insomnia risk. 3

• Taper risperidone gradually over 1-2 weeks to minimize withdrawal symptoms and monitor for symptom recurrence. 2

Critical Safety Considerations

Seizure Risk

• Bupropion lowers seizure threshold—do not use if patient has seizure disorder or conditions predisposing to seizures. 3, 4

• The combination of bupropion with sertraline and risperidone has been associated with spontaneous seizures in case reports, though this occurred in the context of ECT. 4

• Do not exceed 300 mg/day of bupropion SR to minimize seizure risk. 3

Serotonin Syndrome Risk

• The combination of bupropion and SSRIs (like sertraline) carries a documented risk of serotonin syndrome, though rare. 5

• Bupropion inhibits cytochrome P450 2D6, which can increase sertraline blood levels and precipitate serotonin syndrome. 5

• Monitor closely for serotonin syndrome symptoms in the first 24-48 hours after adding bupropion: confusion, agitation, tremors, muscle rigidity, autonomic instability (hypertension, tachycardia, diaphoresis). 1

• Notably, the combination of risperidone and SSRIs has also been associated with serotonin syndrome in elderly patients, so discontinuing risperidone may actually reduce this risk. 6

Drug Interaction Monitoring

• Sertraline interacts with drugs metabolized by CYP2D6, which includes some effects on bupropion metabolism. 1

• Start bupropion at a low dose and increase gradually while monitoring for adverse effects. 3

Special Population Adjustments

• For older adults, start bupropion at 50% of the standard dose (75 mg once daily). 3

• For moderate to severe hepatic impairment, do not exceed 150 mg total daily dose of bupropion. 3

• For moderate to severe renal impairment, reduce total daily bupropion dose by half. 3

Monitoring Schedule

• Schedule follow-up within 2 weeks of initiating the medication switch to assess efficacy and side effects. 3

• Monitor blood pressure at follow-up visits, as bupropion can elevate blood pressure. 3

• Assess for improvement in depressive symptoms after 4-6 weeks on target bupropion dose. 3

• If no response after 6-8 weeks at adequate bupropion dose, consider alternative treatment strategies. 3

• Monitor for neuropsychiatric adverse effects, particularly in patients younger than 24 years. 3

Common Pitfalls to Avoid

• Taking bupropion late in the day significantly increases insomnia risk—emphasize timing with patient. 3

• Exceeding recommended bupropion doses dramatically increases seizure risk. 3

• Abruptly discontinuing risperidone may precipitate symptom relapse if psychotic features were previously present—taper gradually and monitor. 2

• Misinterpreting early serotonin syndrome symptoms (agitation, confusion) as worsening depression and escalating doses rather than discontinuing medications. 5