What are the recommendations for a patient with a history of psychiatric illness considering long-term use of varenicline (Chantix) for smoking cessation?

Long-Term Varenicline Use in Patients with Psychiatric History

Varenicline can be safely used long-term (up to 24 weeks) in patients with psychiatric illness, as the large EAGLES trial demonstrated no increased risk of neuropsychiatric adverse events compared to placebo or nicotine patch in over 4,000 patients with diagnosed psychiatric disorders. 1

Evidence Supporting Safety in Psychiatric Populations

The most definitive evidence comes from a multicenter randomized controlled trial that specifically examined neuropsychiatric safety in two cohorts: patients with diagnosed psychiatric disorders (n=4,074) and those without (n=3,984). 1 Rates of neuropsychiatric adverse events in individuals receiving varenicline were not significantly increased relative to those receiving nicotine patches or placebo in either cohort. 1

Additional supporting evidence includes:

• A reanalysis of 17 placebo-controlled trials (N=8,027) found varenicline did not increase rates of suicidal events, depression, or aggression/agitation, and having a current or past psychiatric illness increased the risk of neuropsychiatric events equally in treated and placebo patients. 2
• A prospective 12-week trial in 112 stable outpatients with schizophrenia showed participants demonstrated improved psychotic symptoms, depressive symptoms, and nicotine withdrawal symptoms from baseline to week 12. 3

Recommended Treatment Duration

For patients who successfully quit during the initial 12 weeks, extend treatment to 24 weeks total (an additional 12 weeks) to significantly increase long-term abstinence rates. 4 This extended approach was validated in a trial of 1,236 smokers and maximizes long-term abstinence. 4

Standard therapy may be extended to 6-12 months to promote continued cessation, though guidelines recommend avoiding longer periods if possible. 1

Dosing and Titration Schedule

Begin varenicline 1-2 weeks before the quit date using this titration schedule to minimize nausea: 1, 4

• Days 1-3: 0.5 mg orally once daily
• Days 4-7: 0.5 mg orally twice daily
• Weeks 2-12: 1 mg orally twice daily (if tolerated)

Flexible dosing strategies allowing patients to self-regulate between 0.5 mg/day and 1 mg twice daily may reduce adverse effects while maintaining efficacy, with maximum dose not to exceed 2 mg/day. 4

Essential Monitoring Requirements

Schedule follow-up within 2-3 weeks after starting pharmacotherapy to assess smoking status and medication side effects, with additional follow-up at 12 weeks and at the end of therapy. 4

Monitor specifically for: 1, 5

• Depression, agitation, behavioral changes, and suicidal ideation throughout treatment
• Seizure activity (instruct patients to discontinue immediately if seizure occurs)
• Nausea (occurs in 28-40% of patients, typically peaks in weeks 1-2 and diminishes over time)
• Insomnia (14%) and abnormal dreams (10-13%)

Discontinue varenicline immediately if any of these neuropsychiatric symptoms develop or worsen. 5

Critical Contraindications and Precautions

Varenicline is absolutely contraindicated in patients with brain metastases due to seizure risk. 1 It should also be avoided in patients with: 4, 5

• History of serious hypersensitivity or skin reactions to varenicline
• History of seizures or conditions that lower seizure threshold (use with extreme caution)

A psychiatric history and suicide risk assessment should be taken before prescription, though current evidence does not support withholding varenicline based solely on psychiatric history. 1

Managing Treatment Failure or Relapse

Patients who previously failed varenicline therapy can be re-treated once factors contributing to the failed attempt are identified and addressed. 4 Varenicline remains effective and well-tolerated for re-treatment, as demonstrated in an RCT of 498 patients. 4

Before restarting, identify and address: 4

• Frequent or intense cravings
• Elevated anxiety, stress, or depression
• Living or working with smokers
• Drug or alcohol use/abuse
• Inadequate behavioral therapy support

If a second course of varenicline fails, switch to combination nicotine replacement therapy before trying subsequent options. 4

Mandatory Behavioral Counseling Integration

Varenicline must always be combined with behavioral counseling for optimal outcomes. 4 Provide a minimum of 4 counseling sessions during the 12-week course, with the first session occurring within the first 2-3 weeks of treatment. 4 Sessions should last 10-30+ minutes, with longer and more frequent sessions linked to higher success rates. 4

Common Pitfalls to Avoid

• Do not confuse varenicline's safety profile with bupropion's: While both carry FDA warnings, bupropion is absolutely contraindicated in patients with seizure disorders (rate of 1/1000), whereas varenicline has only rare seizure risk and can be used cautiously with close monitoring. 1, 6
• Do not dismiss nausea as intolerable: Reassure patients that nausea typically improves after the first 2 weeks and is dose-dependent; the titration schedule specifically addresses this. 4
• Do not withhold varenicline solely based on psychiatric history: The EAGLES trial specifically demonstrated safety in this population. 1
• Do not prescribe without behavioral counseling: Varenicline efficacy is significantly enhanced when combined with counseling support. 4

Comparative Efficacy

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), and demonstrates superior efficacy compared to bupropion (RR 1.39,95% CI 1.25-1.54) and single forms of nicotine replacement therapy (RR 1.25,95% CI 1.14-1.37). 4