Is Wellbutrin (bupropion) safe for smoking cessation in a stable patient with schizophrenia who is currently on Olanzapine (olanzapine)?

Bupropion (Wellbutrin) for Smoking Cessation in Stable Schizophrenia on Olanzapine

Bupropion is safe and effective for smoking cessation in stable schizophrenic patients on olanzapine, with evidence showing it does not worsen psychotic symptoms and significantly improves abstinence rates compared to placebo. 1, 2, 3

Evidence for Safety in Schizophrenia

The combination of bupropion with antipsychotic medications, including olanzapine, has been specifically studied and found to be well-tolerated without worsening clinical symptoms of schizophrenia. 4, 1, 2

• A double-blind placebo-controlled trial demonstrated that bupropion 300 mg/day in schizophrenic patients showed no worsening of positive symptoms and actually trended toward improvement in depressive and negative symptoms 1
• A systematic review and meta-analysis of seven randomized controlled trials confirmed no significant difference in positive (P = 0.28) or negative symptoms (P = 0.49) between bupropion and placebo groups 3
• Patients on atypical antipsychotics (like olanzapine) may actually have enhanced smoking cessation outcomes with bupropion compared to those on typical antipsychotics 2

Efficacy Data

Bupropion significantly increases smoking abstinence rates in schizophrenic patients, with biochemically verified quit rates 2-3 times higher than placebo. 3

• At the end of treatment (week 12), abstinence rates were 36% with bupropion versus 7% with placebo (P = 0.016) 1
• At 6-month follow-up, the risk ratio for abstinence was 2.78 (P = 0.05) favoring bupropion 3
• Expired carbon monoxide levels were significantly lower with bupropion at end of therapy (P = 0.002) 3

Critical Dosing and Administration

Use bupropion SR 150 mg twice daily (300 mg total daily dose) for smoking cessation, starting 1-2 weeks before the target quit date. 5, 6

• Begin with 150 mg once daily for 3 days, then increase to 150 mg twice daily if tolerated 6
• Administer the second dose before 3 PM to minimize insomnia risk 6
• Treatment duration should be 7-12 weeks, with efficacy assessed after this period 5, 6
• The maximum dose must not exceed 300 mg per day for smoking cessation to maintain seizure risk at 0.1% 6, 7

Seizure Risk Considerations

The primary safety concern is seizure risk, which is approximately 1 in 1,000 (0.1%) at recommended doses. 5, 6, 7

Absolute contraindications that preclude bupropion use include: 6, 7

• Active seizure disorder or history of seizures
• Eating disorders (bulimia or anorexia nervosa)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concurrent MAOI use or within 14 days of MAOI discontinuation

Drug Interaction with Olanzapine

Smoking cessation will increase olanzapine blood levels, requiring potential dose adjustment of the antipsychotic. 4

• Smoking induces cytochrome P450 1A2, which metabolizes olanzapine 4
• When patients quit smoking, olanzapine levels can increase by 30-50%, potentially causing increased side effects 4
• Monitor for increased sedation, weight gain, or extrapyramidal symptoms after smoking cessation, and consider reducing olanzapine dose by 10-25% if these occur 4
• This metabolic interaction is independent of bupropion itself and occurs with any successful smoking cessation 4

Monitoring Requirements

Close monitoring is essential during the first few weeks of treatment, particularly for neuropsychiatric symptoms. 5, 7

• Assess for worsening depression, suicidal ideation, agitation, or unusual behavioral changes within 1-2 weeks of initiation 7
• Monitor blood pressure periodically, as bupropion can cause mild elevations 6
• Evaluate psychiatric stability and psychotic symptoms at each visit 1, 2
• Recent large-scale trials show no significant increase in neuropsychiatric events with bupropion compared to nicotine patch or placebo 5

Common Side Effects

Expected side effects include dry mouth, gastrointestinal symptoms, headache, and insomnia, but these do not typically require discontinuation. 2

• These side effects are generally mild and transient 2
• Insomnia can be minimized by avoiding late-day dosing 6

Important Clinical Caveat

Relapse rates are high after bupropion discontinuation, so consider extended treatment duration or transition to maintenance strategies. 1

• The effect of bupropion does not persist after treatment discontinuation 1
• Patients who achieve smoking reduction during treatment can maintain that level at 2 years with appropriate support 4
• Combining bupropion with behavioral interventions significantly improves outcomes 5, 1

Addressing Historical Misconceptions

Some prescribers historically avoided combining bupropion with antipsychotics due to misconceptions about bupropion's pro-dopaminergic activity, but this concern is not supported by clinical evidence. 8

• A database review found that clozapine and long-acting risperidone were prescribed with bupropion significantly less often than expected by chance, suggesting prescriber hesitancy 8
• However, clinical trial data consistently demonstrate safety and efficacy of this combination 1, 2, 3
• Viable treatment options for tobacco use disorder should not be withheld from schizophrenic patients based on theoretical concerns that are contradicted by empirical evidence 8