Can a patient with undifferentiated schizophrenia on clozapine (Clozaril) and flupentixol (Fluanxol) undergo smoking cessation with varenicline (Chantix)?

Varenicline for Smoking Cessation in Schizophrenia Patients on Clozapine and Flupentixol

Yes, varenicline can be safely used for smoking cessation in patients with schizophrenia on clozapine and flupentixol, and is the most effective pharmacotherapy option for this population when combined with behavioral therapy. 1, 2

Evidence for Safety and Efficacy in Schizophrenia

Proven Safety Profile

• A randomized, double-blind, placebo-controlled trial specifically in patients with schizophrenia or schizoaffective disorder (n=127) demonstrated that varenicline was well tolerated with no evidence of exacerbation of psychotic symptoms 1
• There were no significant changes in Positive and Negative Syndrome Scale scores, mood ratings, or anxiety ratings during treatment 1
• Suicidal ideation rates were similar between varenicline (6.0%) and placebo (7.0%) groups, with no completed suicides 1
• An open-label trial of 112 stable outpatients with schizophrenia showed improved psychotic symptoms, depressive symptoms, and nicotine withdrawal symptoms from baseline to week 12 3

Superior Efficacy

• At 12 weeks, 19.0% of varenicline-treated patients achieved smoking cessation versus 4.7% for placebo (p=0.046) in the controlled trial 1
• The open-label study combining varenicline with weekly group cognitive behavioral therapy achieved 47.3% 14-day continuous abstinence and 34% 28-day continuous abstinence rates at week 12 3
• Varenicline is the most effective single pharmacotherapy for smoking cessation, increasing quit odds almost 3-fold compared to placebo (RR 2.24,95% CI 2.06-2.43) 4

Specific Considerations for This Patient

Drug Interactions and Monitoring

• Monitor for neuropsychiatric symptoms including depression, agitation, behavioral changes, and suicidal ideation throughout treatment, though large-scale trials found no significant increase in these events with varenicline 4, 5
• Varenicline does not have significant drug-drug interactions with clozapine or flupentixol, as it is primarily renally excreted 5
• Important caveat: When patients quit smoking, clozapine levels can increase by 50-100% due to loss of CYP1A2 induction by cigarette smoke; monitor clozapine levels and adjust dose accordingly to prevent toxicity 2

Seizure Risk Assessment

• Varenicline carries a rare but significant seizure risk, particularly during the first month of treatment 6, 7
• Clozapine also lowers seizure threshold in a dose-dependent manner 2
• This combination requires careful monitoring but is not contraindicated unless the patient has brain metastases or uncontrolled seizure disorder 4, 7

Recommended Treatment Protocol

Dosing Regimen

• Begin varenicline 1 week before the quit date with the following titration schedule 5:
  • Days 1-3: 0.5 mg once daily
  • Days 4-7: 0.5 mg twice daily
  • Day 8 through week 12: 1 mg twice daily
• Take after eating with a full glass of water to minimize nausea 5

Behavioral Support Requirements

• Provide four or more counseling sessions during the 12-week course, with the first session within 2-3 weeks of starting treatment 4
• Sessions should last 10-30+ minutes, with longer and more frequent sessions linked to higher success rates 4
• This is critical: Placebo response rates in schizophrenia patients are extremely low (2.3-4.7%), making pharmacotherapy essential 1, 2

Follow-up Schedule

• Week 2-3: Assess smoking status, medication side effects, and psychiatric symptoms 4, 6
• Week 12: Assess abstinence and consider extending treatment 4
• Weeks 13-24: For patients who successfully quit, continue varenicline for an additional 12 weeks to increase long-term abstinence 4, 5

Managing Common Side Effects

Nausea (30-40% of patients)

• Typically mild to moderate and diminishes over time 4, 7
• The titration schedule is specifically designed to minimize this effect 4
• Reassure patient that nausea typically improves after the first 2 weeks 4

Sleep Disturbances

• Insomnia occurs in 14-15% of users 7
• Abnormal or vivid dreams occur in 10-13% of users 7
• Consider taking the second dose earlier in the day if sleep disturbances occur 6

Maintenance and Relapse Prevention

• For successful quitters: Extend treatment to 24 weeks total (12 weeks initial + 12 weeks maintenance) to significantly increase long-term abstinence rates 4, 5
• For treatment failures: Patients can be re-treated with varenicline once factors contributing to the failed attempt are identified and addressed 4
• Critical point: Maintenance pharmacotherapy may reduce the high rate of rapid relapse observed upon treatment discontinuation in schizophrenia patients 2

Key Clinical Pitfalls to Avoid

• Do not discontinue antipsychotics during smoking cessation attempts; stable psychiatric treatment is essential for success 1, 3
• Do not forget to monitor and adjust clozapine levels when smoking cessation is achieved, as levels can increase substantially 2
• Do not withhold varenicline due to psychiatric diagnosis alone; controlled trials consistently show no greater rate of neuropsychiatric adverse events than placebo in this population 2
• Do not use varenicline as monotherapy; combination with behavioral therapy is essential for optimal outcomes 4, 3