A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessation. Smoking cessation in women concerned about weight. Weight gain prevention and smoking cessation: cautionary findings. The effects of phenylpropanolamine on dietary intake, physical activity, and body weight after smoking cessation. Effectiveness of a transdermal nicotine system in smoking cessation studies. Effects of phenylpropanolamine on withdrawal symptoms. High-dose nicotine patch therapy. Percentage of replacement and smoking cessation. A placebo controlled randomized trial of the effects of phenylpropanolamine and nicotine gum on cessation rates and postcessation weight gain in women. The nicotine inhaler in smoking cessation. Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Cognitive-behavioral therapy to reduce weight concerns improves smoking cessation outcome in weight-concerned women. 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. Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Bupropion and cognitive behavioral therapy for weight-concerned women smokers. Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. A comparison of the nicotine lozenge and nicotine gum: an effectiveness randomized controlled trial. The efficacy of exercise as an aid for smoking cessation in women: a randomized controlled trial. Effect of nicotine nasal spray on smoking cessation. A randomized, placebo-controlled, double-blind study. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. Efficacy of exercise counselling as an aid for smoking cessation: a randomized controlled trial. The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain. Efficacy of a nicotine lozenge for smoking cessation. 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. The efficacy of moderate-intensity exercise as an aid for smoking cessation in women: a randomized controlled trial. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. The transdermal nicotine patch: results of a randomised placebo-controlled trial. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments. A double-blind trial of a nicotine inhaler 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 proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation. Smoking cessation for weight-concerned women: group vs. individually tailored, dietary, and weight-control follow-up sessions. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. Weight suppression and weight rebound in ex-smokers treated with fluoxetine. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Bupropion for smoking cessation: a randomized trial. A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation. The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial. A randomized trial of smoking cessation. Medication versus motivation. Effects of nicotine gum dose by level of nicotine dependence. Sustained-release bupropion for hospital-based smoking cessation: a randomized trial. Bupropion SR vs placebo for smoking cessation in health care professionals. Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit. Effect of nicotine chewing gum in smoking cessation. A randomized, placebo-controlled, double-blind study. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy. Dose effects of nicotine gum. Efficacy of bupropion alone and in combination with nicotine gum. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Participation in a population-based physical activity programme as an aid for smoking cessation: a randomised trial. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial. A comparison of sustained-release bupropion and placebo for smoking cessation. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation.
Evaluation of the clinical efficacy and safety of a nicotine 2-mg sublingual tablet in smoking cessation.
                A randomized, double-blind, placebo-controlled study of smokers using the 2-mg tablet for 3-6 months with follow-up to 12 months. Dosing was established according to baseline nicotine dependence, scored on the Fagerström Tolerance Questionnaire (FTQ): FTQ > or = 7, two tablets/hour (maximum 40/day); FTQ < 7, one tablet/hour (maximum 20/day).
                Smoking cessation programme in a department of oral and maxillofacial surgery.
                A total of 247 adult smokers, smoking > or = 10 cigarettes/day for > or = 3 years, of whom 123 received active and 124 placebo treatment. The study was powered to detect difference at 6 months.
                Efficacy and safety were evaluated at 6 weeks and 3, 6 and 12 months. Self-reported abstinence was verified by exhaled CO < 10 p.p.m.
                Success rates for complete abstinence (no slips after 2 weeks) for active vs. placebo were 50% vs. 29% at 6 weeks, 42% vs. 23% at 3 months, 33% vs. 18% at 6 months and 23% vs. 15% at 12 months (p < 0.001, 0.001, 0.005 and p = 0.14), respectively. Craving during the first 8 days was significantly reduced among highly dependent smokers on active treatment compared to placebo. Baseline mucosal lesions among abstinent subjects were reduced during the treatment period and at the non-treatment follow-up. Adverse events were mild and tolerable, the most common being irritation and soreness in the mouth and throat.
                The nicotine sublingual tablet increased the smoking cessation rate compared to placebo, reduced craving in highly dependent smokers and was well tolerated. Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt.
                A randomized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program. Participants received the standard smoking cessation program, the program plus nicotine gum, the program plus behavioral weight control, or the program plus both nicotine gum and behavioral weight control. Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment.
                Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum. Weight gain did not vary by treatment condition, so its effect on relapse could not be examined by group. There was no significant relationship between weight gained and relapse in individuals.
                The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates. However, it did not produce the expected effect on weight, thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse. Weight gain is a consistent sequela of smoking cessation. A successful intervention might attract smokers who fear weight gain. If the gain causes smoking relapse, such an intervention might reduce smoking relapse risk.
                Using a sample of 158 smokers who completed a 2-week smoking treatment program, we compared an innovative weight gain prevention intervention with both a nonspecific treatment and standard treatment. Subjects were assessed on weight and smoking behavior and followed for 1 year.
                A disturbing, unexpected finding was that subjects in both the innovative and nonspecific conditions had a higher risk of smoking relapse than did standard treatment subjects. Some differences were observed between abstinent and smoking subjects in weight gain by treatment condition.
                Both active interventions may have been so complicated that they detracted from nonsmoking. Also, caloric restriction may increase the reinforcing value of nicotine, a psychoactive drug, thereby increasing smoking relapse risk. The magnitude of weight gain after smoking cessation may not merit interventions that increase smoking risk. Perhaps attitudinal modifications are the most appropriate. This investigation evaluated the effect of phenylpropanolamine on the weight gain associated with 2 weeks of abstinence from smoking. Subjects were 57 adult female cigarette smokers who were randomly assigned, in a double-blind procedure, to chew gum with phenylpropanolamine or placebo gum, or to chew no gum. After a baseline assessment, subjects were paid to quit smoking for a period of 2 weeks. Forty-one (72%) of the 57 subjects were successful in quitting smoking for the 2-week period. Results indicated that, relative to the other two conditions, abstinent subjects receiving phenylpropanolamine gained 1.5 to 1.9 pounds less weight (p less than 0.05). In addition, abstinence rates were higher (p less than 0.03) and dietary intake lower for subjects receiving phenylpropanolamine (p less than 0.05) relative to the other two conditions. No changes in physical activity were observed. It is concluded that phenylpropanolamine may help reduce weight gain associated with smoking abstinence and in this way may enhance smoking cessation efforts in certain individuals. To investigate the effectiveness and tolerability of a transdermal nicotine system (TNS) as an aid towards easing smoking cessation, two double-blind placebo-controlled randomized field studies were performed. The TNS was available in sizes of 10, 20 and 30 cm2, delivering 7, 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors (Practitioner Study). This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group. The second trial was performed in 112 young people, 56 in each treatment group, at the Universities of Basle and Zurich (University Study). The placebo and the nicotine groups were comparable in both studies. Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system. When abstinence, as verified by CO measurements, was achieved, the next smaller system was applied. In the Practitioner Study, the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks' treatment period took place every 3 weeks. Abstainers in both studies will be followed up until 12 months after treatment was begun. After 1, 2 and 3 months of treatment 41%, 36% and 36% of the participants in the nicotine group of the Practitioner Study were abstinent. The corresponding figures in the placebo group were 19.4%, 20.4% and 22.5%. The differences were statistically significant for all three months (p = 0.001; p = 0.018 and p = 0.043). Body weight did not increase in the TNS group, but did in the placebo group (+ 4.4 kg). The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution. Abstinence rates in the University Study were initially higher with 51.8% in the nicotine group and 28.6% in the placebo group after 3 weeks of treatment, but then declined to 42.9% after 6 weeks and 39.3% after 9 weeks in the nicotine group and to 25% and 19.6%, respectively, in the placebo group. The differences between the groups were statistically significant on all 3 occasions, with p = 0.012, p = 0.046 and p = 0.023.(ABSTRACT TRUNCATED AT 250 WORDS) A prior report (Klesges et al. 1990) suggested that phenylpropanolamine (PPA) was successful in reducing the smoking withdrawal symptom of weight gain in a sample of women. The current investigation evaluates whether the effects of phenylpropanolamine (PPA; up to 10/day PPA gums) on withdrawal symptoms associated with smoking cessation are specific to weight and weight-related symptoms or whether PPA alleviates withdrawal in general. One hundred and seven adult smokers (56 men, 51 women) were randomly assigned, in this double-blind trial, to chew either 8.33 mg phenylpropanolamine gum or a placebo gum. Subjects were then aided to quit smoking for 4 weeks. PPA did not enhance cessation rates. Results from the 47 subjects who successfully quit smoking indicated that postcessation weight gain and ratings of hunger were significantly reduced in both men and women for those assigned to the PPA group relative to the placebo group. Overall, no effects of PPA relative to placebo were observed for other smoking-related withdrawal symptoms. Thus, although PPA appears to reduce weight gain and alleviate weight-related symptoms, no effects on other withdrawal symptoms were observed. Future research directions are suggested. To assess the level of nicotine replacement, evidence of nicotine toxicity, and withdrawal symptom relief with placebo and 11-, 22-, and 44-mg/d doses of transdermal nicotine. A secondary objective was to assess short- and long-term smoking cessation rates.
                Randomized, double-blind, placebo-controlled inpatient/outpatient trial.
                Seventy-one cigarette smokers stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24) smoking rates.
                After baseline measures were obtained, subjects were randomly assigned to placebo or an 11-, 22-, or 44-mg/d dose of transdermal nicotine and admitted to a special hospital unit for intensive inpatient treatment of nicotine dependence. During the 6-day inpatient stay, daily nicotine and cotinine levels were determined from trough and peak blood samples. Outpatient patch therapy continued for 7 weeks following the hospital stay, and those initially assigned to placebo were randomly assigned to 11 or 22 mg/d. At week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d.
                Percentage of replacement of cotinine was calculated by dividing the steady-state levels attained during patch therapy by the corresponding baseline levels. Abstinence from smoking was verified by expired air carbon monoxide. Withdrawal symptoms and nicotine toxicity were assessed daily through questionnaires during the inpatient stay. Follow-up visits were at 3, 6, 9, and 12 months.
                There was a statistically significant relationship between baseline smoking rate and baseline trough and peak blood cotinine levels (rs = 0.39, rs = 0.45; P < .001 in both instances). A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief. Only one subject (a light smoker assigned to the 44-mg dose) developed signs of nicotine toxicity. There was a positive association between the week 2 patch dose and the biochemically confirmed abstinence at the end of patch therapy (P = .007) but not for subsequent follow-up times. A higher percentage of cotinine replacement was associated with the higher 8-week smoking abstinence rate (P = .03), an association not found at long-term follow-up.
                A 44-mg/d dose of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette smoking rates can be used to estimate the initial nicotine patch dose. Monitoring blood cotinine levels at baseline and steady state can be used for assessing the adequacy of nicotine replacement. Withdrawal symptom relief can be improved with more complete nicotine replacement. Achieving a greater percentage of nicotine replacement may increase the efficacy of nicotine patch therapy. With smoking prevalence rates beginning to decline, studies designed to promote cessation in more challenging populations, like weight-concerned smokers, warrant attention. This study assessed the efficacy of two forms of pharmacotherapy [nicotine and phenylpropanolamine (PPA) gums] in addition to a 13-week cognitive behavioral smoking cessation program targeted for women. Participants were 439 females who met rigorous screening criteria and were randomized to one of the three treatment intervention groups (PPA gum, nicotine gum, or placebo gum). All participants attended a 13-week cognitive behavioral smoking cessation program and were given specific instructions on gum chewing. At posttest (13 weeks), and 6- and 12-month follow-ups, body weight and point prevalence abstinence were assessed. Analyses to determine potential differences between treatment groups on weight change and cessation rates were performed. Results indicated that neither change in body weight nor cessation rates significantly differed between groups. Attendance to sessions did appear to consistently increase the likelihood of quitting smoking at posttest and at each of the follow-ups. These results suggest that although the pharmacological interventions had no effect on cessation rates and postcessation weight gain, the behavioral component of the intervention was effective in increasing the odds of quitting smoking in weight-concerned women. Future efforts should focus on increasing adherence to behavioral program components, particularly session attendance. Nicotine replacement therapy has been shown to improve success rates in smoking cessation treatment. However, the available products cause adverse effects, which prevent some smokers from using them. A new method of delivering nicotine via inhaler supplies nicotine orally through inhalation from a plastic tube. This mode of delivering nicotine resembles smoking, as it includes handling and active inhalation.
                To assess the efficacy and safety of the nicotine inhaler as an aid in smoking cessation.
                A 1-year, randomized, double-blind, placebo-controlled study was conducted in a smoking cessation clinic. Two hundred forty-seven smokers who smoked at least 10 cigarettes per day and who had previously made a serious attempt to stop smoking using nicotine chewing gum were recruited through advertisements. Randomization to treatment or control conditions were made at the first group session, with 123 participants receiving nicotine inhalers and 124 receiving placebo inhalers. The inhalers were distributed at the second session and participants were allowed to use the inhalers for 6 months.
                Biochemically verified continuous abstinence from smoking after 2 and 6 weeks and at 3, 6, and 12 months.
                Significantly more participants who had used the nicotine inhalers were continuously abstinent compared with those who had used the placebo inhalers. The respective success rates after 12 months were 28% and 18% (P = .046). At 6 months, 20 participants (16%) in the nicotine group were still using the inhaler, compared with 4 (3%) in the control group (P < .001).
                The nicotine inhaler was an effective smoking cessation aid that produced a few mild and transient adverse effects. The transdermal nicotine patch has proved an effective aid to smoking cessation. The ease of securing good compliance gives it a potential advantage over nicotine gum as an adjunct to brief advice and support in primary care settings where the major public health impact is obtained. In a preliminary report of half the sample of a randomized placebo controlled trial, we showed the patch to be effective in a general practice setting. We report here the definitive results of the full sample, including dose effects, predictors of outcome and other issues of theoretical and practical interest. A total of 1200 heavy smokers (> or = 15 per day), attending 30 general practices in 15 English counties received brief GP advice, a booklet and 16 hours per day patch treatment for 18 weeks. Dose increase and abrupt vs. gradual reduction of patch dosage were also randomized and follow-ups conducted at 1, 3, 6, 12, 26 and 52 weeks. Outcome was measured by self-reported complete abstinence from week 3 to 52 with biochemical validation at all follow-up points. Nicotine patch treatment doubled the rate of continuous abstinence up to 1 year (nicotine 9.6%, placebo 4.8%, p < 0.01); it most likely worked by reducing withdrawal symptoms. It enhanced cessation during the first week and reduced relapse during the second week. The dose increase after week 1 produced no sustained increase in cessation. Gradual reduction was no better at preventing relapse than abrupt withdrawal of patches after week 12. Whether relapse would have increased by ending treatment at some point between weeks 3 and 12 was not tested. Although pre-treatment dependence on cigarettes was prognostic of failure, the patches were equally helpful to both highly and less dependent smokers. Patches were particularly helpful to smokers with pre-treatment subclinical dysthymic symptoms. All but one of the 96 subjects eventually achieving long-term abstinence in the study quit during the first week of cessation. Women smokers concerned about weight gain (N = 219) were randomly assigned to 1 of 3 adjunct treatments accompanying group smoking cessation counseling: (a) behavioral weight control to prevent weight gain (weight control); (b) cognitive-behavioral therapy (CBT) to directly reduce weight concern, in which dieting was discouraged; and (c) standard counseling alone (standard), in which weight gain was not explicitly addressed. Ten sessions were conducted over 7 weeks, and no medication was provided. Continuous abstinence was significantly higher at posttreatment and at 6 and 12 months of follow-up for CBT (56%, 28%, and 21%, respectively), but not for weight control (44%, 18%, and 13%, respectively), relative to standard (31%, 12%, and 9%, respectively). However, weight control, and to a lesser extent CBT, was associated with attenuation of negative mood after quitting. Prequit body mass index, but not change in weight or in weight concerns postquit, predicted cessation outcome at 1 year. In sum, CBT to reduce weight concerns, but not behavioral weight control counseling to prevent weight gain, improves smoking cessation outcome in weight-concerned women. 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. We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment. Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation.
                A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm.
                Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch).
                Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch. We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers.
                In a randomized, double-blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated.
                Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.
                Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns. Trial Registration clinicaltrials.gov Identifier: NCT00006170. Despite the well-documented efficacy and different pharmacokinetic and pharmacodynamic properties of different forms of nicotine replacement therapy, empirical data are insufficient to guide practitioners in selecting a particular form of treatment for individual patients with tobacco dependence.
                To evaluate the comparative efficacy of transdermal nicotine and nicotine nasal spray and identify predictors of treatment outcome.
                Randomized, open-label clinical trial with a 6-month follow-up period.
                2 university-based smoking cessation research programs.
                299 treatment-seeking smokers who were followed for 6 months after the target quit date.
                Behavioral group counseling and 8 weeks of therapy with nicotine nasal spray or transdermal nicotine.
                Demographic characteristics, smoking history, depression symptoms, and body mass index were measured at baseline. Smoking practices were biochemically verified at the end of treatment and at 6 months after the target quit date.
                Abstinence rates for the transdermal nicotine and nicotine nasal spray groups were not significantly different at 6-month follow-up (15.0% vs. 12.2%, respectively; P > 0.2). Interactions in abstinence rates for subgroups of smokers were statistically significant (P < 0.05). Smokers who had low to moderate dependence levels, were not obese, and were white achieved higher abstinence rates with transdermal nicotine, whereas smokers who were highly dependent, obese, or members of minority groups achieved higher abstinence rates with nasal spray.
                The subgroup findings need confirmation in additional large studies before they are routinely applied.
                Ethnicity, weight, and level of nicotine dependence may help identify smokers who have greater or lesser abstinence rates with either transdermal or nasal spray nicotine. Both the nicotine gum and nicotine lozenge have been shown to increase smoking cessation rates, but no published trials have directly compared the two. Higher dose nicotine gum has been recommended as a treatment that may reduce cessation-related weight gain. DESIGN/OUTCOME: In a diverse urban setting, 408 participants were randomized to receive either the lozenge or the gum for 8 weeks of treatment. Seven-day point prevalence of smoking abstinence was biochemically confirmed by exhaled carbon monoxide levels of less than 10 ppm measured at 8 weeks with follow-up at 6 and 12 months.
                At 8 weeks, the lozenge quit rate was 15.1% and the gum quit rate was 11.3%, with an odds ratio of 1.39, 95% confidence interval (0.78-2.49) P=0.26. These rates compare favorably to a historical spontaneous quit rate of 5%. Quit rate comparisons were similarly non-significant at 6 and 12 months. At 8 weeks, successful quitters in the lozenge group gained 3.0+/-6.3 lbs compared to the gum group, which gained 8.4+/-9.2 lbs with t=-2.4, P=0.02, but this finding was not sustained at 6 and 12 months.
                The gum and lozenge appear equally effective for smoking cessation; however, for patients concerned about preventing cessation related to immediate weight gain, the lozenge may be the better agent. Smoking prevalence rates among women are declining at a slower rate than among men.
                To determine if exercise, a healthful alternative to smoking, enhances the achievement and maintenance of smoking cessation.
                Two hundred eighty-one healthy, sedentary female smokers were randomly assigned to either a cognitive-behavioral smoking cessation program with vigorous exercise (exercise) or to the same program with equal staff contact time (control). Subjects participated in a 12-session, group-based smoking cessation program. Additionally, exercise subjects were required to attend 3 supervised exercise sessions per week and control subjects were required to participate in 3 supervised health education lectures per week. Abstinence from smoking was based on self-report, was verified by saliva cotinine level, and was measured at 1 week after quit day (week 5), end of treatment (week 12), and 3 and 12 months later (20 and 60 weeks after quit day, respectively).
                Compared with control subjects (n = 147), exercise subjects (n = 134) achieved significantly higher levels of continuous abstinence at the end of treatment (19.4% vs 10.2%, P = .03) and 3 months (16.4% vs 8.2%, P=.03) and 12 months (11.9% vs 5.4%, P=.05) following treatment. Exercise subjects had significantly increased functional capacity (estimated VO2 peak, 25+/-6 to 28+/-6, P<.01) and had gained less weight by the end of treatment (3.05 vs 5.40 kg, P = .03).
                Vigorous exercise facilitates short- and longer-term smoking cessation in women when combined with a cognitive-behavioral smoking cessation program. Vigorous exercise improves exercise capacity and delays weight gain following smoking cessation. Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all smokers can use the nicotine gum or nicotine patch owing to side effects. In addition, the absorption of nicotine from these formulas is slow compared with smoking. A nicotine nasal spray delivers nicotine more rapidly. The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation.
                Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren's Hospital, Göteborg, Sweden. Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks. At their first group session, subjects were randomized to a group receiving nicotine spray (n = 125), 0.5 mg of nicotine per single spray, or to a placebo group (n = 123). The procedure was double blind. Success rates were measured up to 12 months. The nonsmoking status was verified by expired carbon monoxide less than 10 ppm.
                Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group (27% vs 15%; odds ratio, 2.16; 95% confidence interval, 1.15 to 4.12). Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year. Mild or moderate side effects were rather frequent for both sprays, but they were significantly more for the nicotine spray. Subjects with high scores (> 7) on Fagerström's tolerance questionnaire had a significantly lower success rate with placebo than with the nicotine spray. For subjects with low scores, there was no difference.
                Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation. To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year.
                Placebo controlled, double blind trial.
                Reykjavik health centre.
                237 smokers aged 22-66 years living in or around Reykjavik.
                Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment.
                Sustained abstinence from smoking.
                Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected].
                Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch. To examine whether exercise counselling increases smoking abstinence and reduces tobacco withdrawal and gains in weight and body fat.
                A randomized controlled trial.
                A community-based stop smoking clinic.
                Two hundred and ninety-nine male and female smokers.
                Participants were assigned randomly to a 7-week smoking cessation programme, including nicotine replacement therapy plus either (i) exercise counselling, or (ii) health education advice with equal contact time as for the exercise counselling condition.
                Six weeks of smoking abstinence was confirmed by expired carbon monoxide.
                There was no significant difference in smoking abstinence between the exercise group (n = 154) and the controls (n = 145) at 6 weeks (39.6% versus 38.6%), nor was there any difference in gains in weight or body fat, although those in the exercise group increased their exercise levels. Exercise participants reported less tension, anxiety and stress than the controls during the first week of smoking abstinence (P = 0.03, 0.01 and 0.04, respectively), less irritability throughout 2 weeks of abstinence (P = 0.03), and less restlessness throughout 3 weeks of abstinence (P = 0.04).
                Adding brief exercise counselling to a smoking cessation programme did not increase smoking abstinence or reduce gains in weight or body fat significantly, although exercise levels were raised and there were some beneficial effects on psychological symptoms. To evaluate the efficacy of a combination of ephedrine and caffeine on smoking cessation rates, postcessation weight gain, and withdrawal symptoms and to examine changes in glycosylated hemoglobin (HbA1c) after smoking cessation.
                This randomized double-blind placebo-controlled study with a 1-year follow-up period was carried out at the Department of Pulmonary Medicine in Denmark. Study subjects were 225 heavy smokers who wanted to quit smoking without gaining weight. Two-thirds of the subjects were randomized to receive 20 mg ephedrine plus 200 mg caffeine three times a day; one-third of the subjects received placebo treatment. The dosage was gradually decreased from week 12 to discontinuation at week 39. Group support and control were performed at entry and after 1, 3, 6, 12, 26, 39, and 52 weeks. Main outcome measures were (1) self-reported abstinence with validation by carbon monoxide in expired air and serum cotinine and (2) weight gain.
                The success rates after 1 year were 17% in the group treated with ephedrine plus caffeine and 16% in the group treated with placebo; the success rates were not significantly different at any time. The success rates for the four counseling physicians varied between 7% and 27% after 1 year (p < 0.05). The weight gain was significantly lower in the ephedrine plus caffeine-treated group during the first 12 weeks, but weight gains were similar after 1 year. No differences in the smoking withdrawal symptoms could be observed between the treatment groups. HbA1c was lower 6 weeks and 1 year after smoking cessation (p < 0.05).
                We found an effect of this combination of ephedrine and caffeine on weight gain during the first 12 weeks, but we found no effect on the success rates or craving for cigarettes. Since nicotine gum was introduced in the 1980s, nicotine replacement therapy has become the most widely used pharmacological smoking cessation treatment. Some smokers prefer acute oral forms, but many smokers reject chewing gum. We tested the safety and efficacy of a new nicotine polacrilex lozenge for smoking cessation.
                Double-blind, placebo-controlled, randomized clinical trial with parallel arms testing 2- and 4-mg nicotine lozenges. Smokers (n = 1818) were assigned to a lozenge dose on the basis of nicotine dependence, assessed by time to the first cigarette of the day. Low-dependence smokers were randomized to receive the 2-mg nicotine (n = 459) or placebo (n = 458) lozenge; high-dependence smokers, the 4-mg nicotine (n = 450) or placebo (n = 451) lozenge. We assessed abstinence at 6, 12, 24, and 52 weeks and analyzed craving and withdrawal symptoms.
                Treatment with the nicotine lozenge resulted in significantly greater 28-day abstinence at 6 weeks, for the 2-mg (46.0% vs. 29.7%; odds ratio [OR], 2.10; 95% confidence interval [CI], 1.59-2.79; P<.001) and the 4-mg (48.7% vs. 20.8%; OR, 3.69; 95% CI, 2.74-4.96; P<.001) lozenges, compared with placebo. Significant treatment effects were maintained for a full year. Smokers who used more lozenges achieved significantly better treatment effects. Use of the active lozenge also resulted in reduced craving and withdrawal. Most adverse events were moderate and resembled those seen with nicotine gum.
                The nicotine lozenge is a safe and effective new treatment for smoking cessation in low- and high-dependence 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. Evidence suggests that vigorous-intensity exercise interventions may be effective for smoking cessation among women; however, few studies have examined the efficacy of a moderate-intensity exercise program. The present study examined the efficacy of moderate-intensity exercise for smoking cessation among female smokers. Healthy, sedentary female smokers (N = 217) were randomly assigned to an 8-week cognitive-behavioral smoking cessation program plus moderate-intensity exercise (CBT+EX) or to the same cessation program plus equal contact (CBT). A subsample received nicotine replacement therapy. Results indicated that the CBT+EX and CBT groups were equally likely to attain smoking cessation at the end of treatment, as measured by cotinine-verified 7-day point-prevalence abstinence (20.2% for CBT+EX vs. 18.5% for CBT). The CBT+EX group was more likely to report smoking cessation, as measured by 7-day point prevalence at the 3-month follow-up (11.9% vs. 4.6%, p<.05), compared with the CBT group. No group differences were found at 12 months by either 7-day point prevalence (7.3% for CBT+EX vs. 8.3% for CBT) or continuous abstinence (0.9% for CBT+EX vs. 0.9% for CBT). Additionally, among participants in the CBT+EX group, those with higher adherence to the exercise prescription were significantly more likely to achieve smoking cessation at the end of treatment than were participants reporting lower adherence to exercise. Our findings indicate that the empirical support for moderate-intensity exercise as an adjunctive treatment to CBT for smoking cessation may be limited. Perhaps future studies could compare moderate- vs. vigorous-intensity physical activity to test their relative efficacy. 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. To evaluate the efficacy of the transdermal nicotine patch as an aid to smoking cessation when used as an adjunct to a cognitive-behavioural group intervention and to assess the effectiveness of the patch in ameliorating withdrawal symptoms.
                Double-blind placebo-controlled randomised trial with six months' follow-up of those who returned to the hospital-based outpatients smoking cessation clinic.
                Three hundred and thirteen smokers recruited from the local community. Mean age was 42 years, 48% were male, mean cigarette consumption was 29 per day and mean duration of smoking was 24 years.
                Cognitive-behavioural intervention delivered in a group context, two hours once a week over five weeks, self-help manual, and 24-hour daily nicotine patch treatment for 10 weeks.
                Point prevalence abstinence at three and six months, and sustained cessation from end of treatment to six months, with biochemical validation (expired carbon monoxide). We examined the effectiveness of the nicotine patch in ameliorating specific withdrawal symptoms by self-report of degree of severity.
                The active nicotine patch resulted in significantly higher biochemically confirmed abstinence rates when compared with placebo at three months (48% v. 21%) and at six months (33% v. 14%). Six-months' continuous abstinence rates were also significantly higher among the active nicotine group (25%) compared with placebo (12%). The most common adverse events among active patch users were sleep disturbance and local skin irritation. The nicotine patch reduced the severity of some withdrawal symptoms. A low level of dependence was the strongest predictor of three and six months' abstinence.
                The transdermal nicotine patch is effective when used as an adjunct to a group cognitive-behavioural intervention and it provides relief from withdrawal symptoms associated with nicotine dependence. The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates. To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments.
                Two independent randomized placebo-controlled double-blind trials.
                Smoking cessation clinic.
                Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking.
                Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2).
                Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving).
                Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking.
                Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms. To evaluate the efficacy of a new nicotine inhaler system for smoking cessation.
                A 1-year, randomized, double-blind, placebo-controlled study.
                Medical outpatient clinic with physicians experienced in smoking cessation assistance.
                A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper.
                Subjects were randomly allocated to nicotine inhalers (n = 145) or placebo (n = 141) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support.
                Continuous smoking abstinence at weeks 6, 12, 24, and 52, verified by measurements of carbon monoxide in expired air.
                Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group. The respective success rates were 28% and 12% after 6 weeks, 21% and 9% after 12 weeks, 17% and 8% after 6 months, and 15% and 5% after 1 year (P = .02 to .001). The mean nicotine substitution based on cotinine determinations after 2 weeks was 43% (SD, 45%) of smoking levels. The treatment was well tolerated, and no serious adverse events were reported.
                In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts. 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. St John's wort is an effective antidepressant that can reduce tobacco withdrawal symptoms, but it is not known whether it assists cessation. Chromium assists weight loss and might limit post cessation weight gain.
                In a factorial design, we randomised smokers stopping smoking to 900 mg St John's wort (SJW) active or placebo and also randomised them to 400 microm chromium or placebo daily. Treatment started 2 weeks prior to quit day and continued for 14 weeks. Participants and researchers were blind to treatment allocation. All participants received weekly behavioural support. The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting.
                6/71 (8.5%) participants on active SJW and 9/72 (12.5%) on placebo achieved prolonged abstinence at 4 weeks, an odds ratio (OR) (95% confidence interval) of 0.65 (0.22-1.92). At 6 months, 3 (4.2%) SJW active and 6 (8.3%) SJW placebo participants were still abstinent, an OR of 0.49 (0.12-2.02). Among these participants, the mean difference in weight gain between active chromium and placebo was -0.8 1kg (-3.79 to 2.18) at 4 weeks and -3.88 kg (-12.13 to 4.38) at 6 months.
                Taking together the absolute quit rates, the small difference between active and placebo, and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation. Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain, but the point estimate indicates a potentially worthwhile benefit. Postcessation weight gain is of concern to many female cigarette smokers. A multidisciplinary treatment combining psychological, dietary, and exercise components followed a 2-week smoking cessation program. Participants were randomly assigned to receive six follow-up relapse prevention sessions (in a group format or in an individually tailored format) directed by trained representatives from clinical psychology, dietary counseling, and exercise physiology. As predicted, abstinence rates were significantly higher among the individually tailored follow-up participants than among those assigned to the group follow-up condition at 3 and 6 months posttreatment. Differences between conditions in postcessation weight gain were not significant. However, the postcessation weight gain that did occur was significantly associated with subsequent smoking relapse in the group follow-up condition only. 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. Fluoxetine's effect (30 mg, 60 mg, and placebo) on postcessation weight gain was studied among participants from a randomized, double-blind 10-week smoking cessation trial who met strict criteria for abstinence and drug levels. It was hypothesized that (a) fluoxetine would dose-dependently suppress postcessation weight gain and (b) drug discontinuation would produce dose-dependent weight rebound. During the on-drug phase, placebo participants gained weight linearly (M = 2.61 kg). exceeding both fluoxetine groups (30-mg group M = 1.33 kg, 60-mg group M = 1.25 kg). Weight suppression was initially greater for 60 mg than 30 mg, but both were followed by weight gain. Six months off drug produced greater dose-dependent weight rebound for 60 mg than 30 mg or placebo. Considering both on- and off-drug phases, weight gain for 60 mg of fluoxetine (M = 6.5 kg) was comparable with that for placebo (M = 4.7 kg) but greater than that for 30 mg (M = 3.6 kg). Fluoxetine appears to forestall postcessation weight gain, allowing time for the weight-conscious smoker to focus on quitting smoking rather than on preventing weight gain. A transdermal nicotine patch, which delivers 0.7 mg/cm2 per 24 h and is available in sizes of 10, 20, and 30 cm2 was tested in subjects from 21 general medical practices in a 3-month, placebo-controlled randomised double-blind study. The nicotine group (n = 100) and the placebo group (n = 99) were similar at entry. Participants who smoked more than 20 cigarettes a day were treated with the 30 cm2 patch and the others with the 20 cm2 patch. When abstinence, defined as smoking 0-3 cigarettes per week and verified by CO measurement, was achieved, the next smallest patch was applied. After 1, 2, and 3 months of treatment 41, 36, and 36%, respectively, in the nicotine group were abstinent. The corresponding figures in the placebo group were 19, 20, and 23%. The differences were significant for all 3 months. Body weight did not increase in the nicotine group, but in the placebo group the mean increase was 4.4 kg. Craving and withdrawal symptoms decreased more with nicotine substitution for cigarettes. The patches were generally well tolerated, although 25% of subjects in the nicotine group and 13% in the placebo group had transient local erythema after application of the patch; 5 members of the nicotine group withdrew because of poor cutaneous tolerance. Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy.
                A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates.
                During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36).
                In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates. The use of nicotine chewing gum combined with psychological support improves the success rate in quitting smoking. We studied the safety and efficacy of a transdermal nicotine patch in smoking cessation.
                We conducted a double-blind randomized study comparing the effects of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks.
                Rates of sustained abstinence were significantly better with active treatment than with placebo: 53, 41, 24, and 17 percent of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5, and 4 percent of those in the placebo-patch group (P less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch had to withdraw from the study because of side effects.
                The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with placebo. However, the absolute rate of abstinence after one year was only 17 percent, which is lower than the rate in studies that have combined the use of nicotine chewing gum with behavioral therapy. 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. A prospective randomized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation.
                Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep University between September 2002 and July 2003. Of these, only 131 patients fulfilled the trial criteria. We randomized the patients into nicotine patch (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24 weeks. Questionnaires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation. Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria.
                Success rates were 26% for nicotine patch group, 26% for bupropion and 16% for control group at the end of the 24th week (p=0.56). Beck depression inventory scores did not differ significantly between the groups, however none of the cases with scores greater than 13 succeeded regardless of the group. Mean body weight at baseline and change at 6 months did not differ significantly between the groups. Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group (p=0.008).
                The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation, and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects. We used the Heaviness of Smoking Index, a subset of the Fagerstrom Test for Nicotine Dependence, to classify 608 cigarette smokers planning a cessation attempt as low or high in nicotine dependence. Subjects within each level of dependence were then randomly assigned to placebo, 2-mg, or 4-mg nicotine gum treatment. Subjects were also provided brief (5-10 min per visit) behavioral counseling during a 1-year period of follow-up. At 1 year post-cessation, quit rates were 11.2, 19.5, and 18.4% for low-dependence smokers receiving placebo, 2-mg, and 4-mg gum, respectively (plinear trend = 0.20). For high-dependence smokers, quit rates at 1 year were 6.1, 15.7, and 20.7% for the placebo, 2-mg, and 4-mg gum conditions, respectively (plinear trend = 0.002). The interaction of nicotine-gum dose and dependence group was not significant (p = 0.42), nor did the 2-mg and 4-mg doses differ significantly in effectiveness, though both 2-mg and 4-mg gum were significantly more effective than placebo gum. We also found a significant dose-related effect for nicotine gum to moderate post-cessation heart-rate decline. Other variables related to abstinence at 1 year post-cessation were a longer period of abstinence on a prior quit attempt, being married, higher education level, and having a non-smoking spouse or significant other. Results indicate that nicotine gum is a significant aid to smoking cessation, more than doubling the odds of successful cessation compared to the odds for placebo-gum users. The 4-mg dose provided a non-significant increase in cessation rates for high-dependence smokers. Smoking history and demographic variables also have a significant impact on the outcome of a quit-smoking attempt. Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers.
                We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates.
                At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12).
                The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions. To evaluate bupropion SR for smoking cessation in physicians and nurses.
                This double-blind prospective 26-center, 12-country trial randomized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks. The participants were followed for 52 weeks.
                Bupropion SR was superior to placebo (50% vs 40%, P=0.013) on the 4-week primary outcome variable. Due to a high placebo response in this health care population, statistical differences were not maintained after treatment was discontinued.
                Bupropion SR is effective and well tolerated in health care professionals. Relapse prevention measures are needed to attain long-term abstinence. To determine whether attempts to prevent weight gain will increase success rates for stopping smoking.
                16 week, open, randomised study with 1 year follow up.
                Obesity unit.
                287 female smokers who had quit smoking before but started again because of weight concerns.
                Combination of a standard smoking cessation programme with nicotine gum and a behavioural weight control programme including a very low energy diet. A control group was treated with the identical programme but without the diet. Main outcome measure: Sustained cessation of smoking.
                After 16 weeks, 68/137 (50%) women had stopped smoking in the diet group versus 53/150 (35%) in the control group (P=0.01). Among these women, weight fell by mean 2.1 (95% confidence interval 2.9 to 1.3) kg in the diet group but increased by 1.6 (0.9 to 2.3) kg in the control group (P<0.001). After 1 year the success rates in the diet and control groups were 38/137 (28%) and 24/150 (16%) respectively (P<0.05), but there was no statistical difference in weight gain.
                Combining the smoking cessation programme with an intervention to control weight helped women to stop smoking and control weight. The effect of 2-mg nicotine chewing gum as an adjunct to group therapy for smoking cessation was studied in a placebo-controlled, double-blind, randomized trial. After one year, 29% of the 106 subjects treated with nicotine chewing gum had remained abstinent throughout the year compared with 16% of the 99 subjects treated with placebo. The results were confirmed by measurement of levels of expired CO. More subjects in the nicotine group (70/94 v 45/93) reported that the gum reduced the craving for smoking. The adverse effects were few and not serious. In the nicotine group, 3% were still using the nicotine gum after two years. No subjects in the placebo group used the chewing gum beyond six months. Nicotine chewing gum is effective in improving the success rates in smoking cessation based on group therapy. 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 attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation. Nicotine gum has been shown to be effective in improving abstinence rates, and in reducing post-cessation withdrawal distress and weight gain. However, the dose effects of nicotine gum on these outcomes is not known. In the present study, we varied the amount of 2 mg nicotine gum prescribed to motivated quitters to explore the hypotheses (a) that motivated quitters would use more pieces of gum when coached and counseled to do so and (b) that there would be a dose-related effect of gum use on abstinence, withdrawal symptoms, and weight gain. One hundred seventy-seven volunteers were assigned to chew either 0, 7, 15, or 30, pieces per day of 2 mg nicotine gum. Biological verification of gum use and smoking abstinence were assessed in community volunteers who attended an intensive behavioral counseling program for smoking cessation while using nicotine gum for 3 months. In the survival analysis at 12 weeks, gum-group assignment was not related to successful abstinence. In the subset of 42 abstinent subjects, there was a strong positive relationship between pieces per day of nicotine gum used and saliva cotinine. However, there was substantial variability in groups of subjects reporting similar amounts of gum use. Withdrawal symptom reporting was not related to either gum use or cotinine levels. Weight gain was significantly related in a dose-dependent manner to salivary cotinine levels, but not to gum group assignment, with high and low cotinine subjects gaining on average, 4.0 and 6.6 pounds, respectively. Discussion of the use of high levels of nicotine gum is addressed. Consistent with earlier work, the study provided further support for the relationship between nicotine replacement level and post-cessation weight gain. In this double-blind, placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at 1 week, end of treatment, and 6 months but not at 12 months postquit. After the first week postquit there were no differences in abstinence rates between the AA and AP groups. We found no significant individual difference variables that moderated outcome beyond 1 week postquit. 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. Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting. Low participation in vigorous-intensity physical activity programmes precludes their population-wide applicability. In a randomised controlled trial, we tested whether a population-based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy.
                Participants (n=481; 57% male; mean age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy. In addition, participants in the physical activity group (n=229) also took part in a programme of moderate-intensity physical activity implemented at the national level, and offering nine weekly 60-minute sessions of physical activity. To ensure equal contact conditions, participants in the control group (n=252) attended weekly 60-minute health behaviour education sessions unrelated to physical activity. The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up.
                Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups, respectively (p=0.06).
                Participation in a population-based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates. A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group.
                ClinicalTrials.gov; US National Institutes for Health (available online at http://clinicaltrials.gov/; Clinical Trial Registration Number: NCT00521391). Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose.
                Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers.
                We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence.
                The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers. Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.
                Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.
                The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).
                For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.
                Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.
                At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.
                A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year. 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. To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting.
                Randomised, double blind, placebo controlled trial with follow up for 26 weeks.
                629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling. Smokers were motivated to quit smoking for a second time and smoked > or = 15 cigarettes a day.
                Twelve weeks' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits.
                Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations.
                At 12 weeks 21/315 (6.7%) subjects allocated to active treatment had stopped smoking compared with 6/314 (1.9%) allocated to placebo (absolute difference 4.7%; 95% confidence interval 1.6% to 7.9%; P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and 8/314 (2.6%) (3.8%; 0.6% to 7.0%; P = 0.021). Difficulty in sleeping was reported by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015). Severe reactions at the site of application were rare (6/322; 1.9%).
                Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed, moderate to heavy smokers. Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective. The likelihood of severe reactions at the site of application with repeated treatment is low. 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.
Although some pharmacotherapies tested to limit PCWG show evidence of short-term success, other problems with them and the lack of data on long-term efficacy limits their use. Weight management education only, is not effective and may reduce abstinence. Personalised weight management support may be effective and not reduce abstinence, but there are too few data to be sure. One study showed a VLCD increased abstinence but did not prevent WG in the longer term. CBT to accept WG did not limit PCWG and may not promote abstinence in the long term. Exercise interventions significantly reduced weight in the long term, but not the short term. More studies are needed to clarify whether this is an effect of treatment or a chance finding. Bupropion, fluoxetine, NRT and varenicline reduce PCWG while using the medication. Although this effect was not maintained one year after stopping smoking, the evidence is insufficient to exclude a modest long-term effect. The data are not sufficient to make strong clinical recommendations for effective programmes to prevent weight gain after cessation.