What is the efficacy of Chantix (varenicline)?

From the Guidelines

Chantix (varenicline) is the most effective single pharmacotherapy option for smoking cessation, increasing the odds of quitting by almost 3-fold compared to placebo. This is based on the findings of a Cochrane network meta-analysis, which reported an odds ratio (OR) of 2.88 (95% CI, 2.40–3.47) for varenicline compared to placebo 1. The efficacy of varenicline has been consistently demonstrated in various studies, including a double-blind randomized clinical trial (RCT) that showed varenicline-treated patients achieved higher abstinence rates than those receiving placebo, nicotine patch, or bupropion 1.

Key Points

• Varenicline works by partially mimicking the effects of nicotine in the brain's reward center and competitively inhibiting the binding of nicotine from cigarettes 1.
• The standard treatment regimen for varenicline typically consists of a 1-week titration, followed by 1 mg twice daily for 12 weeks 1.
• Common side effects of varenicline include nausea, sleep disturbances, headache, and constipation 1.
• Varenicline may also be efficacious for smoking reduction, with a clinical trial showing that a 24-week course of varenicline effectively promoted smoking cessation in patients who were unwilling to quit but willing to gradually reduce cigarette consumption 1.

Clinical Considerations

• Patients with severe kidney disease may require dose adjustments, and those with a history of psychiatric conditions should be monitored closely as varenicline can occasionally worsen mood disorders or cause behavioral changes 1.
• A recent RCT examined whether a biomarker of nicotine clearance (nicotine metabolite ratio [NMR]) was predictive of nicotine patch versus varenicline efficacy in “slow” versus “normal” metabolizers of nicotine, suggesting the possibility of optimizing treatment selection based on this biomarker in the future 1.

From the FDA Drug Label

The efficacy of varenicline in smoking cessation was demonstrated in six clinical trials in which a total of 3659 chronic cigarette smokers (≥10 cigarettes per day) were treated with varenicline. In all clinical studies, abstinence from smoking was determined by patient self-report and verified by measurement of exhaled carbon monoxide (CO≤10 ppm) at weekly visits Among the varenicline-treated patients enrolled in these studies, the completion rate was 65%. Forty-five percent of patients receiving varenicline 1 mg per day (0. 5 mg twice daily) and 51% of patients receiving 2 mg per day (1 mg twice daily) had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% of patients in the placebo group In addition, 31% of the 1 mg per day group and 31% of the 2 mg per day group were continuously abstinent from one week after TQD through the end of treatment as compared to 8% of the placebo group.

The efficacy of Chantix (varenicline) in smoking cessation is supported by six clinical trials, with CO-confirmed continuous abstinence rates of:

• 45% for patients receiving 1 mg per day
• 51% for patients receiving 2 mg per day
• Compared to 12% in the placebo group Key findings include:
• Completion rate: 65% among varenicline-treated patients
• Abstinence rates: 31% of patients receiving 1 mg per day and 31% of patients receiving 2 mg per day were continuously abstinent from one week after the target quit date through the end of treatment 2

From the Research

Efficacy of Chantix (Varenicline)

• Chantix (varenicline) is an effective aid to smoking cessation therapy, with significantly higher continuous abstinence rates compared to placebo or bupropion sustained-release 3, 4, 5, 6, 7.
• Varenicline has been shown to attenuate the urge to smoke, negative affect withdrawal symptoms, and the reinforcing effects of smoking 3, 4, 6.
• The odds of remaining abstinent were 2.7 to 3.1 times higher with 12 weeks of varenicline treatment than with placebo 3.
• Varenicline treatment also─as compared to placebo─significantly delayed smoking relapse and increased the likelihood of long-term abstinence 4, 6, 7.

Clinical Trial Results

• In two identical, randomized, double-blind, phase III clinical trials, 12 weeks of treatment with varenicline 1 mg twice daily was associated with significantly higher abstinence rates over weeks 9-12 than sustained-release bupropion 150 mg twice daily or placebo 4.
• A separate phase III trial found that an additional 12 weeks of treatment in smokers achieving abstinence in the first 12 weeks was associated with greater abstinence through to week 52 than placebo treatment 4.
• Varenicline treatment was also associated with significantly higher rates of abstinence than placebo treatment in randomized, double-blind, clinical trials in smokers in China, Japan, Korea, Singapore, Taiwan, and Thailand 4.

Safety and Tolerability

• Varenicline treatment was generally well tolerated in study populations with no major comorbidities 4, 5.
• The most common adverse events associated with varenicline were nausea, insomnia, and headache 4, 5, 7.
• Postmarketing surveillance has raised concerns about the potential risk of neuropsychiatric adverse outcomes, including behavior change, agitation, depressed mood, and suicidal ideation and behavior 7.