Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial. A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Behavioral counseling and varenicline treatment for smoking cessation. Placebo-controlled trial of cytisine for smoking cessation. Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial. A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline. A randomized controlled open comparative trial of varenicline vs nicotine patch in adult smokers: efficacy, safety and withdrawal symptoms (the VN-SEESAW study).
Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.
                A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.
                During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.
                Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation. The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.
                To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.
                Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.
                Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.
                Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.
                For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).
                Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.
                clinicaltrials.gov Identifier: NCT00141206. We assessed the safety of long-term varenicline administration for smoking cessation.
                In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits.
                A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo).
                Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy. The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation.
                This multicenter, double-blind, placebo-controlled study randomized healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n = 129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52.
                Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P<.001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group (22.4%; P<.001) and the 0.5-mg group (18.5%; P<.001) vs placebo (3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation.
                Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation. The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder.
                Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans.
                A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks (short-term treatment) and 8 weeks (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects.
                Outpatient clinics.
                A total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Intervention Varenicline.
                Prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention.
                A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P = .006), (2) reduced startle reactivity (P = .02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P = .03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners' Continuous Performance Test. Clinically, there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose).
                Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits. Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.
                To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).
                A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.
                Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.
                Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).
                During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).
                Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.
                clinicaltrials.gov Identifier: NCT00143364. Smoking is the most important risk factor for COPD and accelerates its progression. Despite the health implications, a large proportion of patients with COPD continue to smoke, so finding effective smoking cessation interventions for this population is paramount. To our knowledge, this is the first randomized clinical trial to compare the efficacy and safety of varenicline tartrate vs placebo in smokers with mild to moderate COPD.
                In a 27-center, double-blind, multinational study, 504 patients with mild to moderate COPD (postbronchodilator FEV1/FVC, <70%; FEV1 percent predicted normal value, ≥50%) and without known psychiatric disturbances were randomized to receive varenicline (n=250) or placebo (n=254) for 12 weeks, with a 40-week nontreatment follow-up. The primary end point was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. A secondary end point was CAR for weeks 9 to 52.
                CAR for weeks 9 to 12 was significantly higher for patients in the varenicline group (42.3%) than for those in the placebo group (8.8%) (OR, 8.40; 95% CI, 4.99-14.14; P<.0001). CAR in the patients treated with varenicline remained significantly higher than in those treated with placebo through weeks 9 to 52 (18.6% vs 5.6%) (OR, 4.04; 95% CI, 2.13-7.67; P<.0001). Nausea, abnormal dreams, upper-respiratory tract infection, and insomnia were the most commonly reported adverse events (AEs) for patients in the varenicline group. Serious AEs were infrequent in both treatment groups. Two patients in the varenicline group and one patient in the placebo group died during the study. Reports of psychiatric AEs were similar for both treatment groups.
                Varenicline was more efficacious than placebo for smoking cessation in patients with mild to moderate COPD and demonstrated a safety profile consistent with that observed in previous trials. Trial registry: ClinicalTrials.gov; No.: NCT00285012; URL: www.clinicaltrials.gov. The majority of cigarette smokers who achieve abstinence relapse within the first year and require many attempts before achieving permanent abstinence. Evidence to support pharmacological treatment for relapse prevention is insufficient.
                To determine whether smokers who quit after 12 weeks of treatment with varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, maintain greater continuous abstinence rates (defined as not a single "puff" of a cigarette) than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation.
                Randomized controlled trial conducted at multiple medical clinics in 7 countries with follow-up to 52 weeks after study baseline. Of 1927 cigarette smokers recruited between April 2003 and February 2004 and treated for 12 weeks with open-label varenicline titrated to 1 mg twice per day, 1236 (64.1%) did not smoke, use tobacco, or use nicotine replacement therapy during the last week of treatment and 62.8% (n = 1210) were randomized to additional treatment or placebo.
                Participants were randomly assigned to receive either double-blind varenicline, 1 mg twice per day (n = 603), or placebo (n = 607) for an additional 12 weeks.
                Carbon monoxide-confirmed continued abstinence during weeks 13 to 24 and weeks 13 to 52 of the study.
                The carbon monoxide-confirmed continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 (70.5% vs 49.6%; odds ratio [OR], 2.48; 95% confidence interval [CI], 1.95-3.16; P<.001) as well as for weeks 13 to 52 (43.6% vs 36.9%; OR, 1.34; 95% CI, 1.06-1.69; P = .02). Adverse events reported in the open-label period were mostly mild; no difference in adverse events between varenicline and placebo was observed during the double-blind period.
                Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were randomized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo. This advantage was maintained through the nontreatment follow-up to week 52. Varenicline may be an efficacious, safe, and well-tolerated agent for maintaining abstinence from smoking.
                clinicaltrials.gov Identifier: NCT00143286. Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial alpha4beta2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown.
                A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug.
                Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984. To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation.
                320 healthy, motivated-to-quit smokers (> or =10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2-12: 0.5-2.0 mg/day).
                Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward.
                Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n=155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p<0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p<0.001), 24 (32.5 vs. 13.5%; p<0.001), and 52 (28.0 vs. 13.5%; p=0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations.
                A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation. Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.
                In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24.
                Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively).
                Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. Smoking remains the primary preventable cause of death and illness in the U.S. Effective, convenient treatment programs are needed to reduce smoking prevalence.
                This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline.
                Current treatment-seeking smokers (n=1202) were recruited from a large healthcare organization between October 2006 and October 2007. Eligible participants were randomized to one of three smoking-cessation interventions: web-based counseling (n=401); proactive telephone-based counseling (PTC; n=402); or combined PTC and web counseling (n=399). All participants received a standard 12-week FDA-approved course of varenicline. Self-report determined the primary outcomes (7-day point prevalent abstinence at 3- and 6-month follow-ups); the number of days varenicline was taken; and treatment-related symptoms. Behavioral measures determined utilization of both the web- and Phone-based counseling.
                Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months (38.9%, 48.5%, 43.4%) and at 6 months (30.7%, 34.3%, 33.8%) for the web, PTC, and PTC-web groups, respectively. The PTC group had a significantly higher percentage of abstinence than the web group at 3 months (OR=1.48, 95% CI=1.12, 1.96), but no between-group differences in abstinence outcomes were seen at 6 months.
                Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence, but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline.
                2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. Cytisine, a partial agonist that binds with high affinity to the α(4)β(2) nicotinic acetylcholine receptor, is a low-cost treatment that may be effective in aiding smoking cessation. This study assessed the efficacy and safety of cytisine as compared with placebo.
                We conducted a single-center, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive cytisine or matching placebo for 25 days; participants in both groups received a minimal amount of counseling during the study. The primary outcome measure was sustained, biochemically verified smoking abstinence for 12 months after the end of treatment. Of 1542 adult smokers screened, 740 were enrolled and 370 were randomly assigned to each study group.
                The rate of sustained 12-month abstinence was 8.4% (31 participants) in the cytisine group as compared with 2.4% (9 participants) in the placebo group (difference, 6.0 percentage points; 95% confidence interval [CI], 2.7 to 9.2; P=0.001). The 7-day point prevalence for abstinence at the 12-month follow-up was 13.2% in the cytisine group versus 7.3% in the placebo group (P=0.01). Gastrointestinal adverse events were reported more frequently in the cytisine group (difference, 5.7 percentage points; 95% CI, 1.2 to 10.2).
                In this single-center study, cytisine was more effective than placebo for smoking cessation. The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally. Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern.
                The primary objective of this study was to evaluate the efficacy and dose-response relationship of varenicline in Japanese smokers.
                In this double-blind, placebo-controlled, randomized, parallel-group study, subjects were randomized to receive varenicline at 0.25 mg BID, 0.5 mg BID, 1 mg BID, or placebo for 12 weeks followed by a 40-week, nontreatment follow-up phase. The primary efficacy variable was the continuous abstinence rate (CAR), defined as no reported smoking (not even a puff) or other nicotine use and confirmed by end-expiratory carbon monoxide level <or=10 ppm, during the last 4 weeks of treatment (weeks 9-12). Secondary end points included CARs for weeks 9-24 and 9-52. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire on Smoking Urges, and the modified Cigarette Evaluation Questionnaire. The tolerability of varenicline was also evaluated.
                Of 618 subjects who received treatment, 515 (83.3%) were classified as nicotine dependent (scoring >or=5 on the Tobacco Dependence Screener), and constituted the primary analysis group. Of these, 385 (74.8%) subjects were male, and the mean age was within the range of 39.0 to 40.2 years. Across treatment groups, subjects claimed to have smoked a mean of 23.1 to 24.9 cigarettes per day in the preceding 30 days, and the mean score on the Fagerström Test for Nicotine Dependence was within the range from 5.4 to 5.7. The CAR for weeks 9-12 was significantly higher for all doses of varenicline compared with placebo (39.5% [51/129]). The highest CAR of 65.4% (85/130) was achieved with varenicline 1 mg BID (odds ratio [OR] [95% CI] = 2.98 [1.78-4.99]; P < 0.001). The CAR for weeks 9-52 was significantly greater for varenicline 1 mg BID than placebo (34.6% [45/130] vs 23.3% [30/129]; OR [95% CI] = 1.81 [1.04-3.17]; P = 0.036). The CARs for weeks 9-24 at 0.25, 0.5, and 1 mg BID were 33.6% (43/128), 35.2% (45/128), 37.7% (49/130), and for weeks 9-52 at 0.25 and 0.5 mg BID were 27.3% (35/128) and 28.9% (37/128) but failed to reach significance versus the placebo (29.5% [38/129] for weeks 9-24 and 23.3% [30/129] for weeks 9-52). Treatment-emergent adverse events (AEs) were more prevalent among varenicline-treated subjects (79.1% [121/153] at 0.25 mg BID, 80.6% [125/155] at 0.5 mg BID, and 80.1% [125/156] at 1 mg BID) than placebo subjects (71.4% [110/154]). The 3 most prevalent AEs at varenicline 1 mg BID were nasopharyngitis (35.9% [56/156]), nausea (24.4% [38/156]), and headache (10.3% [16/156]), all of which were of mild or moderate intensity. Nausea was the only AE that appeared dose related (7.2% [11/153] at 0.25 mg BID, 9.7% [15/155] at 0.5 mg BID, and 24.4% [38/156] at 1 mg BID) versus placebo (7.8% [12/154]).
                Varenicline was associated with dose-dependent improvement in smoking abstinence rates during the last 4 weeks of treatment and in the longer term over 40 weeks of nontreatment follow-up. The dose associated with the highest efficacy was varenicline 1 mg BID. The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention. The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4β2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes. Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young.
                This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea.
                A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan. Eligible subjects, smoking >or=10 cigarettes/d, received brief smoking-cessation counseling and were randomly assigned in a 1:1 ratio to varenicline 1 mg BID (titrated during the first week) or placebo. Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide <or=10 ppm. The primary end point was continuous abstinence rate (CAR) during the last 4 weeks of treatment. Secondary end points included CAR from weeks 9 to 24 and 7-day point prevalence (PP) of abstinence at weeks 12 and 24. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire of Smoking Urges, and the modified Cigarette Evaluation Questionnaire. Observed or volunteered adverse-event data were recorded at clinic visits.
                Overall, 126 subjects (84.9% male) received varenicline, and 124 (92.7% male) received placebo, Subjects were aged 21 to 73 years (mean age, 39.7 and 40.9 years for varenicline and placebo groups, respectively), and the mean (range) body weights were 69.0 (44.8-110.0) kg and 71.4 (45.5-102.0) kg, respectively. Subjects had smoked for 3 to 52 years (mean, 20.2 and 22.1 years in the varenicline and placebo groups, respectively). Subjects had smoked a mean of 23 cigarettes/d over the past month, with 51.6% (varenicline) and 46.0% (placebo) having made 1 or more prior serious quit attempts. Smoking-cessation rates at the end of treatment were 59.5% with varenicline versus 32.3% with placebo (P < 0.001). CARs through 12 weeks post-treatment (weeks 9-24) were 46.8% with varenicline and 21.8% with placebo (P < 0.001). The 7-day PP was 67.5% with varenicline versus 36.3% with placebo at week 12, and 57.1% versus 29.0% with placebo at week 24 (both, P < 0.001). Treatment-emergent, all-causality adverse events with an incidence >or= 5% for varenicline were nausea (43.7% for varenicline vs 11.3% placebo), insomnia (15.1% vs 13.7%), increased appetite (7.9% vs 6.5%), constipation (7.1% vs 2.4%), anxiety (5.6% vs 2.4%), and abnormal dreams (5.6% vs 0.8%). Adverse events resulted in <10% treatment discontinuations overall.
                Varenicline was an efficacious and well-tolerated pharmacotherapy for smoking cessation in this group of Asian smokers over a 12-week treatment period, and its effects persisted for a further 12-week follow-up period. The hospital can be an important opportunity for smoking cessation interventions. This is the first randomized, double-blinded, placebo-controlled pilot trial utilizing varenicline and post-discharge, in-person behavioral treatment for hospitalized smokers.
                Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009. The primary outcome was biochemically confirmed abstinence at 24 weeks following discharge. Secondary outcomes included withdrawal symptoms, motivation, utilization of treatment, and medical events.
                Overall abstinence at 24 weeks was 27% with no difference between varenicline and placebo treatment groups (23% vs. 31%). There were no significant differences in motivation to stop smoking or withdrawal symptoms. Over 40% of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not (53.1% vs. 8.5%, p<0.01). Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group (25% vs. 5%; p<0.01). Twenty-three subjects were re-hospitalized with no significant differences between treatment groups (13 varenicline vs. 10 placebo).
                This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation, produced some hypothesis-generating findings, and suggested the potential benefit of face-to-face treatment following discharge.
                Copyright © 2011 Elsevier Ltd. All rights reserved. It has been suggested that anti-smoking therapy gives encouraging results, but this has not been verified by well-randomized study protocols. The present study was a randomized controlled trial of varenicline vs nicotine patch in adult smokers for comparison of efficacy, safety and withdrawal symptoms.
                The 32 adult smokers were randomly divided into a varenicline group (VG, n=16) and a nicotine patch group (NG, n=16). The primary endpoints were the 12- and 24-week smoking-abstinence rates, safety and withdrawal symptoms including stress. No significant difference in abstinence rates was observed between the 2 groups over weeks 9-12 (71.4% vs 78.6% in the VG and NG, respectively), and weeks 9-24 (64.3% vs 71.4%, respectively). The frequencies of inability to concentrate at 2, 4, and 8 weeks, and wakeful nights at 2 weeks were higher in the VG than in the NG. Adverse side-effects associated with a gastrointestinal disorder occurred in 14 cases and 1 case in the VG and NG, respectively, and skin allergy was seen in 0 and 9 cases, respectively.
                The selection of treatment depends on the balance of desired acuteness of cessation of smoking and side-effects, such as psychiatric and gastrointestinal problems or skin allergy.
Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out.

Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.