Should I continue Wellbutrin (bupropion) and naltrexone in a patient with schizoaffective disorder who presents with psychosis due to methamphetamine use?

Discontinue Wellbutrin Immediately in This Patient with Active Methamphetamine-Induced Psychosis

You should discontinue bupropion (Wellbutrin) immediately in this patient presenting with active psychosis due to methamphetamine use, as bupropion can precipitate or worsen psychotic symptoms, particularly in vulnerable populations with schizoaffective disorder. Naltrexone can be continued as it poses minimal risk and may help with substance use disorder. 1, 2, 3

Rationale for Discontinuing Bupropion

Risk of Bupropion-Induced Psychosis

• Bupropion has dopaminergic effects that can precipitate or worsen psychosis, particularly in patients with preexisting psychotic disorders like schizoaffective disorder 2, 3
• The literature demonstrates that bupropion-induced psychotic episodes occur in approximately one-third of cases in patients with histories of psychiatric conditions, including mood and psychotic disorders 1
• Higher doses of bupropion (300 mg/day) are more likely to be associated with severe psychotic outcomes, and the combination of methamphetamine use (which is also dopaminergic) creates a dangerous synergistic risk 2
• Psychotic symptoms from bupropion typically manifest with auditory, visual, or cenesthetic hallucinations (85% of cases), often accompanied by delusional episodes and restlessness 1

Protective Role of Antipsychotics

• The critical distinction is that concurrent use of antipsychotics at adequate doses appears to be protective against bupropion-induced psychosis 2, 3
• However, in your patient presenting with active methamphetamine-induced psychosis, the antipsychotic coverage is clearly inadequate at this moment, making bupropion continuation dangerous 3
• A systematic review found that 229 schizophrenic patients on stable antipsychotic regimens were successfully treated with bupropion without developing psychosis, but this requires stable baseline psychiatric status 3

Management of Naltrexone

Continue Naltrexone

• Naltrexone can be safely continued as it does not have dopaminergic effects and may actually help with methamphetamine use disorder 4
• Naltrexone has been studied as adjunctive treatment in patients with schizophrenia and comorbid substance abuse, with evidence suggesting potential benefit 4
• The naltrexone-bupropion combination is being investigated for methamphetamine use disorder, but this is in the context of stable patients without active psychosis 5

Immediate Clinical Actions

Acute Psychosis Management

• Initiate or optimize antipsychotic treatment immediately for the methamphetamine-induced psychosis using a benzodiazepine or conventional/atypical antipsychotic as monotherapy 6
• For acute agitation, consider using haloperidol, droperidol, or a benzodiazepine (lorazepam or midazolam) as effective monotherapy 6
• Use an antipsychotic as both management of agitation and initial drug therapy for this patient with known schizoaffective disorder 6

Timeline for Bupropion Discontinuation

• Discontinue bupropion immediately without tapering given the acute psychotic presentation 1
• Expect complete remission of bupropion-related psychotic symptoms within an average of 10 days after discontinuation 1
• Note that bupropion-induced psychotic episodes share similarities with acute organic or toxic psychosis, particularly amphetamine-induced psychosis 1

When Bupropion Might Be Reconsidered

Future Reintroduction Criteria

• Bupropion could potentially be reconsidered only after the patient achieves stable psychiatric status on an adequate antipsychotic regimen for at least 4 weeks 6, 3
• The patient must be completely abstinent from methamphetamine with documented negative urine drug screens 2
• Close monitoring for psychotic symptoms would be mandatory if bupropion is ever reintroduced 3
• Consider alternative smoking cessation or depression treatments that don't carry dopaminergic risks in this vulnerable population 1

Critical Pitfalls to Avoid

• Do not continue bupropion during active psychosis, even if the patient was previously stable on it, as the combination of methamphetamine use and bupropion creates compounded dopaminergic stimulation 2, 3
• Do not assume the psychosis is solely from methamphetamine if bupropion is on board—both contribute to the clinical picture 1
• Do not restart bupropion until psychiatric stability is achieved and documented for at least 4 weeks on therapeutic antipsychotic doses 6, 3