Efficacy of Varenicline for Cigarette Reduction Before Quitting in Japanese Smokers: A Subpopulation Analysis of the Reduce to Quit Trial.

PURPOSE: This prospective analysis of the Japanese subpopulation of the varenicline reduce to quit study was conducted to evaluate whether results for Japanese participants were consistent with the full study population. METHODS: Patients received varenicline or placebo for a 24-week treatment period (12-week smoking reduction phase then a 12-week smoking abstinence phase) followed by a 28-week nontreatment, follow-up phase. Participants were to reduce the daily number of cigarettes smoked by at least 50% by week 4 and by a further 50% by week 8, with the goal of achieving complete abstinence by week 12. The primary efficacy end point was the carbon monoxide-confirmed continuous abstinence during weeks 15 to 24. FINDINGS: Overall, 210 Japanese patients were randomly assigned to 1 of the 2 study groups (varenicline, 107; placebo, 103). Continuous abstinence rates for weeks 15 to 24 were higher for participants in the varenicline group versus the placebo group (46.7% vs 12.6%; odds ratio = 14.68; 95% CI, 5.38-40.05), and the 7-day point prevalence of abstinence rates were higher for varenicline versus placebo at week 12 (odds ratio = 13.76; 95% CI, 5.28-35.86). The number of participants with a ≥50% reduction in the number of daily cigarettes smoked from baseline to week 4 and a ≥75% reduction by week 8 was greater in the varenicline group versus the placebo group (week 4: 59.8% vs 30.1%; week 8: 38.3% vs 12.6%). Serious adverse events were reported in 3.7% of varenicline participants and 1.0% of placebo participants. IMPLICATIONS: The efficacy and tolerability results of this analysis are consistent with those of the full varenicline reduce to quit study. Varenicline treatment and cigarette reduction before quitting may provide an alternative approach to smoking cessation in Japanese smokers who are not ready to quit immediately. ClinicalTrials.gov identifier: NCT01370356.

Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial.

IMPORTANCE: Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting. OBJECTIVE: To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising. INTERVENTIONS: Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks. MAIN OUTCOMES AND MEASURES: Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52. RESULTS: The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07). CONCLUSIONS AND RELEVANCE: Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01370356.

A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: Effective smoking cessation treatments are needed for patients with schizophrenia, who, compared with the general population, have high rates of cigarette smoking and more difficulty quitting. We evaluated the safety and efficacy of varenicline for smoking cessation in outpatients with stable schizophrenia or schizoaffective disorder. METHOD: In this 12-week, randomized, double-blind, multicenter trial (May 8, 2008, to April 1, 2010), 127 smokers (≥ 15 cigarettes/d) with DSM-IV-confirmed schizophrenia or schizoaffective disorder received varenicline or placebo (2:1 ratio). The primary outcome was safety and tolerability of varenicline assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks. Abstinence was defined as no smoking 7 days prior to weeks 12 and 24, verified by carbon monoxide level. RESULTS: Eighty-four participants received varenicline; 43, placebo. At 12 weeks (end of treatment), 16/84 varenicline-treated patients (19.0%) met smoking cessation criteria versus 2/43 (4.7%) for placebo (P = .046). At 24 weeks, 10/84 (11.9%) varenicline-treated and 1/43 (2.3%) placebo-treated patients, respectively, met abstinence criteria (P = .090). Total adverse event rates were similar between groups, with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings. Rates of suicidal ideation adverse events were 6.0% (varenicline) and 7.0% (placebo) (P = 1.0). There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides. CONCLUSIONS: Varenicline was well tolerated, with no evidence of exacerbation of symptoms, and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks. Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00644969.