Varenicline Group Research Articles

A Double-Blind Randomized Placebo-Controlled Pilot Study of Neuropsychiatric Adverse Events in Abstinent Smokers Treated with Varenicline or Placebo

Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline. One hundred ten smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM-IV) were randomized to 12 weeks of varenicline 1 mg twice daily (n = 55) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety, aggression, and irritability were measured at baseline and weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Scale (HAM-A), and the Overt Aggression Scale-Modified (OAS-M). The Profile of Mood States (POMS) was administered daily. Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods. Participants' mean baseline characteristics were 33 years of age, 22 cigarettes/day and Fagerström Test for Nicotine Dependence score > 7. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo = .03, 95% confidence interval [CI] -.68-.73; NS), HAM-A (treatment difference [TD] = .14, 95% CI -.62-.90; NS), OAS-M Aggression subscale (TD = .5, 95% CI -1.18-2.18; NS), OAS-M Irritability subscale (TD = .08, 95% CI -.17-.34; NS), and the POMS total scores (TD = .5, 95% CI -.52-1.53; NS). There were no significant differences between groups on measures of depressive symptoms, anxiety, or aggression/hostility. Systematically solicited NPAEs were similar between the varenicline and placebo groups.

The Safety and Efficacy of Varenicline in Cocaine Using Smokers Maintained on Methadone: A Pilot Study

In this double-blind, placebo-controlled trial, we compared varenicline (2 mg) to placebo for treatment for cocaine and tobacco dependence in 31 methadone-maintained subjects. Subjects received weekly counseling during the 12-week study participation. Our results indicate that varenicline is safe to give to this subject population, as there were no adverse events related to medication during this study. Varenicline was no more effective than placebo for abstinence from cocaine. Treatment with varenicline was associated with a reduced number of cigarettes smoked per day, even though subjects received only a brief education for smoking cessation. The self-report reduction in smoking was corroborated by CO levels and the Fagerström Test of Nicotine Dependence. However, self-ratings of positive mood on the Positive Affect Negative Affect Schedule did significantly decrease in the varenicline group as compared to the placebo group, although this appears to be due to randomization differences related to lifetime depression diagnosis. These preliminary findings may point to potential therapeutic value of varenicline for smoking cessation in cocaine users maintained on methadone.

Varenicline treatment for smoking cessation in Asian populations: a pooled analysis of placebo-controlled trials conducted in six Asian countries

Objective:A pooled analysis to evaluate the efficacy and safety of varenicline versus placebo for smoking cessation in Asian populations. A secondary objective was to compare the data to pooled trials among predominantly Western populations.Research design and methods:Smokers (n = 893) in three randomized, double-blind, placebo-controlled, multicenter, phase IIb or III trials conducted in six Asian countries (Japan, Taiwan, Korea, China, Singapore, and Thailand), received varenicline (1 mg twice daily; n = 447) or placebo (n = 446) for 12 weeks. Non-treatment follow-up lasted 12 weeks (40 weeks in Japan). Primary endpoint was the carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9–12 (last 4 weeks of treatment). Secondary endpoint was CAR for weeks 9–24.Results:CAR was higher for varenicline than placebo during weeks 9–12 (58.6 vs. 34.3%; odds ratio [OR]: 2.74; 95% confidence interval [CI]: 2.08–3.60; p < 0.0001), and through 12 weeks of follow-up (CAR weeks 9–24; 41.4 vs. 25.3%; OR: 2.08; 95% CI: 1.56–2.77; p < 0.0001). The most frequent adverse events (AEs) in the varenicline group (greater incidence than the placebo group) were: nausea (31.5%), headache (8.5%), dizziness (7.8%), insomnia (7.4%), and upper abdominal pain (5.4%). Serious AEs occurred in four varenicline and five placebo participants. Discontinuations due to AEs occurred in 3.6% of varenicline and 1.6% of placebo participants. Compared with the Western studies, abstinence rates for both varenicline and placebo were numerically higher in the Asian studies, although treatment effects were similar between the two populations. AEs reported in the Asian trials were largely similar to those in the Western populations.Conclusions:Varenicline significantly improved smoking abstinence in Asian populations from six countries. AEs were predominantly of mild or moderate intensity. These data were largely the same as those seen in Western populations, but the studies were not designed to explore racial or cultural differences.

Adherence to treatment for tobacco dependence: Association with smoking abstinence and predictors of adherence

Detailed analysis of adherence to tobacco cessation medications and predictors of adherence is sparse in published literature. In this analysis, we assessed adherence to tobacco dependence treatment, association of adherence with abstinence, and predictors of adherence. We analyzed pooled results from 2 randomized controlled trials. Adult smokers (N = 2,045) who were randomly assigned to 12 weeks of treatment and took at least 1 dose of the assigned medication (varenicline [692], bupropion sustained release [669], or placebo [684]) were included. Treatment adherence was defined as any subject who took >or=1 dose of study drug for >or=80% days during the 12-week treatment period ("completers"). Smoking abstinence was assessed using carbon monoxide-confirmed 4-week continuous abstinence rate at end of treatment (Weeks 9-12). Adherence rates for completers who received varenicline, bupropion, and placebo groups, respectively, were 99.3%, 98.8%, and 99.2%. There was a positive correlation between adherence to treatment and tobacco abstinence in all treatment groups. Treatment effect sizes (odds ratios) for active therapy compared with placebo were similar whether considering all subjects or only the completer subset. Age, cigarettes per day, and Week-2 abstinence were significant predictors of adherence for all treatment groups (all p < .05), with Week-2 abstinence the strongest predictor. Adherence to pharmacotherapy for smoking cessation is highly correlated with improved tobacco abstinence. Early abstinence experience is a strong driver of adherence.

Psychiatric Adverse Events in Randomized, Double-Blind, Placebo-Controlled Clinical Trials of Varenicline

Varenicline (Chantix), Champix) has shown efficacy and tolerability as an aid to smoking cessation. In postmarketing surveillance, neuropsychiatric symptoms have appeared; however, their incidence and causal relationship to varenicline is not known. We assessed the incidence and relative risk (RR) of psychiatric disorders in ten randomized, double-blind, placebo-controlled trials of varenicline for smoking cessation. All smoking cessation phase II, III and IV randomized controlled clinical trials of varenicline versus placebo completed as of 31 December 2008, on file with the manufacturer (Pfizer, Inc.), were included. All studies have been published. All 3091 participants who received at least one dose of varenicline and all 2005 participants who received placebo were included in this analysis. These were men and women smoking > or =10 cigarettes/day, aged 18-75 years and without current psychiatric disease who received varenicline or placebo for 6 (one study), 12 (eight studies) or 52 (one study) weeks. Adverse events were recorded at each study visit and classified according to standard Medical Dictionary for Regulatory Activities (MedDRA) terms (version 11.0). The incidence of psychiatric disorders other than solely sleep disorders and disturbances was 10.7% in subjects treated with varenicline and 9.7% in subjects treated with placebo, with an RR of 1.02 (95% CI 0.86, 1.22). The RRs (95% CI) versus placebo of psychiatric adverse events with an incidence > or =1% in the varenicline group were 0.86 (0.67, 1.12) for anxiety disorders and symptoms, 0.76 (0.42, 1.39) for changes in physical activity, 1.42 (0.96, 2.08) for depressed mood disorders and disturbances, 1.21 (0.79, 1.83) for mood disorders and disturbances not elsewhere classified and 1.70 (1.50, 1.92) for sleep disorders and disturbances. There were no cases of suicidal ideation or behaviour in varenicline-treated subjects in the ten placebo-controlled studies analysed. However, among three trials that were excluded from the analysis because of their open-label design, two cases of suicidal ideation and one completed suicide were reported in patients who had been treated with varenicline. With the exception of sleep disorders and disturbances, there was no evidence of dose-responsivity. There was no significant increase in overall psychiatric disorders, other than sleep disorders and disturbances, in varenicline-treated subjects in this sample of smokers without current psychiatric disorders. Ongoing studies are testing the use of varenicline in psychiatric patients.

Clinical Summaries

Clinical Summaries

Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial.

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.

A Randomized Controlled Open Comparative Trial of Varenicline vs Nicotine Patch in Adult Smokers - Efficacy, Safety and Withdrawal Symptoms (The VN-SEESAW Study) -

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.

Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial

Objective To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.Design Double blind, placebo controlled, parallel group, multicentre,...

Sensitivity Analysis of the Efficacy of Varenicline in Smoking Cessation With a Special Reference to Study Dropouts

AbstractWe conducted a sensitivity analysis under four scenarios using data from three Asian studies conducted with low dropout rates to evaluate the efficacy of varenicline in smoking cessation within a scenario where dropouts from the study are dealt with in a manner as unfavourable as possible to varenicline. Pooled odds ratio of continuous abstinence at week 24 was 1.55 (95% confidence interval: 1.03–2.35, random-effect model) under the scenario where dropouts from the varenicline group were dealt with as smokers and those from the placebo group as successful quitters. From the present study, the efficacy of varenicline has been firmly established in the Asian population.

BRIEF REPORT: Varenicline increases striatal dopamine D2/3 receptor binding in rats

ABSTRACTIncreasing dopamine D2/3 receptor availability is postulated to be a treatment for drug addiction. Varenicline, an α4β2‐nicotinic partial agonist, is effective for nicotine dependence. We hypothesize that varenicline increases dopamine D2/3 receptor availability. Twenty male drug‐naïve rats were randomized to varenicline (2 mg/kg) or placebo for 14 days, and then injected with the dopamine D2/3 radiotracer 123I‐IBZM. We found significantly higher striatum‐to‐cerebellum binding ratios in both dorsal and ventral striatum for the varenicline group compared with placebo. Varenicline increases dopamine D2/3 receptor availability in drug‐naïve rats. Therefore, varenicline may be an effective treatment for addictions other than smoking.

Varenicline for smoking cessation: A placebo‐controlled, randomized study

Varenicline tartrate, a novel, selective, nicotinic acetylcholine receptor partial agonist, has been developed specifically as a smoking cessation drug. This study evaluated the efficacy of a standard regimen of varenicline compared with placebo for smoking cessation in 333 subjects in China, Singapore and Thailand. This 24-week, randomized, double-blind, placebo-controlled trial of varenicline, 1 mg bd, consisted of a 12-week treatment period followed by a 12-week non-treatment follow-up period. The primary study end-point was the 4-week continuous abstinence rate defined as the proportion of subjects who reported total abstinence from smoking and other nicotine products from weeks 9-12. A key secondary end-point was the continuous abstinence rate from weeks 9-24, defined as the proportion of subjects who achieved the primary end-point as well as total abstinence from all tobacco products from weeks 13-24. Both end-points were achieved by a significantly higher proportion of subjects in the varenicline group than in the placebo group. The 4-week continuous abstinence end-point was achieved by 50.3% and 31.6% in the varenicline and placebo groups, respectively (P = 0.0003), while continuous abstinence from weeks 9-24 was achieved by 38.2% and 25.0% of subjects, respectively (P = 0.0080). The treatment effect was generalizable by treatment centre and country. Varenicline was safe and appeared to be well tolerated by most subjects. Varenicline was significantly more efficacious for smoking cessation than placebo over a 12-week treatment period and a further 12-week non-treatment follow-up period in smokers from China, Singapore and Thailand. No significant side-effects were noted.

Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent smokers: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study

Background: Varenicline is approved as an aid to smoking cessation in adults aged ≥18 years. Objective: The goal of this study was to characterize the multiple-dose pharmacokinetics, safety, and tolerability of varenicline in adolescent smokers. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled healthy 12− to 16-year-old smokers (≥3 cigarettes daily) into high-body-weight (>55 kg) and low-body-weight (≤55 kg) groups. Subjects were randomized to receive 14 days of treatment with a high dose of varenicline, a low dose of varenicline, or placebo. The varenicline doses in the high-body-weight group were 1 mg BID and 0.5 mg BID; the varenicline doses in the low-body-weight group were 0.5 mg BID and 0.5 mg once daily. The apparent renal clearance (CL/F) and volume of distribution (V/F) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling. Results: The high-body-weight group consisted of 35 subjects (65.7% male; 77.1% white; mean age, 15.2 years). The low-body-weight group consisted of 37 subjects (37.8% male; 48.6% white; mean age, 14.3 years). The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d. The CL/F for a 70-kg adolescent was 10.4 L/h, comparable to that in a 70-kg adult. The estimated varenicline V/F was decreased in individuals of small body size, thus predicting a varenicline C max ~30% greater in low-body-weight subjects than in high-body-weight subjects. In high-body-weight subjects, steady-state varenicline exposure, as represented by the AUC 0–24, was 197.0 ng · h/mL for varenicline 1 mg BID and 95.7 ng · h/mL for varenicline 0.5 mg BID, consistent with values reported previously in adult smokers at the equivalent doses. In low-body-weight subjects, varenicline exposure was 126.3 ng · h/mL for varenicline 0.5 mg BID and 60.1 ng · h/mL for varenicline 0.5 mg once daily, values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID, respectively. Among high-body-weight subjects, adverse events (AEs) were reported by 57.1% of subjects in both the high- and low-dose varenicline groups and by 14.3% of subjects in the placebo group; among low-body-weight subjects, AEs were reported by 64.3%, 73.3%, and 12.5% of subjects in the high-dose varenicline, low-dose varenicline, and placebo groups, respectively. The most common AEs were nausea, headache, vomiting, and dizziness. Psychiatric AEs that were considered treatment related included abnormal dreams in 2 subjects and mild, transient anger in 1 subject. Of the AEs reported by ≥1 subject in any treatment group, ≥92% were mild in intensity. No subject discontinued the study because of an AE. Conclusions: Varenicline steady-state exposure in study subjects weighing >55 kg was similar to that observed previously in adults. The body-weight effect on varenicline pharmacokinetics, which resulted in higher exposure in individuals of smaller body size (≤55 kg), was adequately offset by administration of half the varenicline dose recommended in adults. Varenicline was generally well tolerated during the 14-day treatment period. Clinical Trials Identification Number: NCT00463918.

A randomized, placebo-controlled trial of varenicline, a selective α 4β 2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers

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.

Partial agonism at nicotinic receptors with varenicline – a new approach to smoking cessation

Cigarette smoking is the leading preventable cause of death. Varenicline is a partial agonist at nicotinic α4β2 receptors being tested for smoking cessation. During a trial in which the drugs were administered for 12 weeks, the continuous abstinence rate was 17.7% in the placebo group, which improved to 29.5% with bupropion SR and to 44.0% with varenicline 1 mg b.i.d. Abstinence rates for weeks 9 through 52 were 8.4, 16.1 and 21.9% for placebo, bupropion and varenicline, respectively. Prolonging the treatment with varenicline may give better quit rates. In this trial, after 12 weeks of open-label varenicline, the abstainers received either another 12 weeks of varenicline or placebo. At week 24, more of the participants in the varenicline group (70.5%) were abstinent than in the placebo group (49.6%). The most common adverse effect in both these trials with varenicline was nausea. This prompted a trial comparing the efficacy and safety of four varenicline dosing regimens, to determine whether a lower dose was effective and with reduced adverse effects. After 52 weeks, the abstinence rates were 3.9% in the placebo group, and higher in the varenicline 0.5 mg b.i.d. (18.5%) and 1 mg b.i.d. groups (22.4%). The rates of nausea were not significantly increased by varenicline 0.5 mg b.i.d., but were by varenicline 1 mg b.i.d. In summary, varenicline may give slightly higher smoking cessation rates than bupropion, but the smoking cessation rates, especially at 52 weeks, remain low.

Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;

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.