Considerations When Adding Bupropion to Antipsychotic Regimens in Schizophrenia or Schizoaffective Disorder
Bupropion should not be used in patients with schizophrenia or schizoaffective disorder who are agitated or have seizure disorders, but can be safely added to stable antipsychotic regimens for treating depression, negative symptoms, or for smoking cessation when proper monitoring is in place. 1
Safety Profile and Risk Assessment
Psychosis Risk
The risk of bupropion-induced psychosis is negligible in patients who are:
- On stable antipsychotic medication
- Using the extended-release formulation (rather than immediate-release)
- Properly monitored 2
93% of reported bupropion-induced psychotic episodes occurred in patients without concomitant antipsychotic medication 2
Seizure Risk
- Bupropion lowers seizure threshold and carries a dose-related seizure risk of 0.4% at recommended doses 3
- Special caution needed when combining with clozapine, which has a cumulative seizure risk of 10% over 3.8 years of treatment 3
- The combination of bupropion and clozapine may have additive or potentially synergistic seizure risk 3
Dosing Protocol
Initial Dosing and Titration
- Start with 37.5 mg every morning
- Increase by 37.5 mg every 3 days
- Maximum recommended dose: 150 mg twice daily 1
- To minimize insomnia risk, administer second dose before 3 PM 1
Special Populations
- For patients with hepatic impairment:
- Moderate to severe impairment: 150 mg every other day
- Mild impairment: Consider reduced dose and/or frequency 4
- For patients with renal impairment:
- Consider reducing dose and/or frequency 4
Clinical Benefits
Depression Management
- Effective for treating depressive symptoms in schizophrenia when added to stable antipsychotic regimens 5
- Activating properties can help improve energy levels 1
Negative Symptoms
- May improve negative symptoms including anhedonia, amotivation, alogia, affective flattening, and passive social withdrawal 6
- Studies show significant improvement in negative symptoms when added to antipsychotic regimens 5
Smoking Cessation
- Significantly increases smoking abstinence rates compared to placebo in patients with schizophrenia 7
- 50% of patients achieved 7-day point prevalence smoking abstinence with bupropion vs. 12.5% with placebo 7
- More effective when combined with atypical antipsychotics 7
Monitoring Protocol
Baseline Assessment
- Evaluate for seizure risk factors
- Document baseline negative and depressive symptoms
- Obtain baseline EEG if possible, especially if combined with clozapine 5
- Screen for agitation and history of seizure disorders 1
Ongoing Monitoring
- Monitor for emergence of psychotic symptoms
- Watch for EEG abnormalities, which occur frequently 2, 5
- Assess for common side effects: dry mouth, gastrointestinal symptoms, headache, and insomnia 7
Common Pitfalls and Contraindications
Absolute Contraindications
- Seizure disorder
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Concomitant use of MAOIs (must wait 14 days after stopping MAOIs before starting bupropion)
- Known hypersensitivity to bupropion 4
Relative Contraindications
- Agitated patients
- Patients with high seizure risk
- Patients not on stable antipsychotic regimens 1
Drug Interactions
- Bupropion inhibits CYP2D6 and can increase concentrations of many antipsychotics
- May require dose adjustment of antipsychotics metabolized by CYP2D6 (e.g., haloperidol, risperidone, thioridazine) 4
- Atypical antipsychotics may enhance smoking cessation outcomes with bupropion 7
By following these guidelines, bupropion can be safely and effectively added to antipsychotic regimens in patients with schizophrenia or schizoaffective disorder to address depression, negative symptoms, or for smoking cessation, while minimizing the risk of adverse events.