Search

Encouraging adult smokers who are uninterested or unwilling to quit, and would otherwise continue to smoke, to transition to potentially less harmful nicotine products such as electronic nicotine delivery systems (ENDS) may positively impact population health. However, counterbalancing this benefit is the societal concern that ENDS may be used by never smokers and youth and serve as a 'gateway' into cigarette smoking. Data were analysed from two independent surveys of the prevalence and perceptions of myblu ENDS use in the United States. Total sample size was 22,232 young adults and 23,264 adults. Being curious to use myblu was 1.6-2.0 times more likely in young adult current smokers than young adult never smokers. This likelihood was 2.8 times greater for adult current smokers compared with adult never smokers in the perceptions survey, while in the prevalence survey, there was no difference between adult current and never smokers. Intentions to use myblu were significantly greater in young adult current smokers compared with young adult never smokers in both surveys and in adults in the prevalence survey. In all surveys and age cohorts, 124 of 45,496 participants (0.1% of the total survey population) reported first using myblu prior to smoking cigarettes and went on to become established smokers. Curiosity and intentions to use myblu were generally higher in current smokers compared with never smokers. There was minimal evidence to suggest the existence of a 'gateway' effect to established cigarette smoking among never-smoking myblu users., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Importance: Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal., Objective: To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo., Design, Setting, and Participants: A 3-group, double-blind, placebo-controlled, randomized trial (ORCA-2) compared 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo, with follow-up to 24 weeks, among 810 adults who smoked cigarettes daily and wanted to quit. It was conducted at 17 US sites from October 2020 to December 2021., Interventions: Participants were randomized (1:1:1) to cytisinicline, 3 mg, 3 times daily for 12 weeks (n = 270); cytisinicline, 3 mg, 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks (n = 269); or placebo 3 times daily for 12 weeks (n = 271). All participants received behavioral support., Main Outcomes and Measures: Biochemically verified continuous smoking abstinence for the last 4 weeks of cytisinicline treatment vs placebo (primary) and from end of treatment to 24 weeks (secondary)., Results: Of 810 randomized participants (mean age, 52.5 years; 54.6% female; mean of 19.4 cigarettes smoked daily), 618 (76.3%) completed the trial. For the 6-week course of cytisinicline vs placebo, continuous abstinence rates were 25.3% vs 4.4% during weeks 3 to 6 (odds ratio [OR], 8.0 [95% CI, 3.9-16.3]; P < .001) and 8.9% vs 2.6% during weeks 3 to 24 (OR, 3.7 [95% CI, 1.5-10.2]; P = .002). For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; P < .001) and 21.1% vs 4.8% during weeks 9 to 24 (OR, 5.3 [95% CI, 2.8-11.1]; P < .001). Nausea, abnormal dreams, and insomnia occurred in less than 10% of each group. Sixteen participants (2.9%) discontinued cytisinicline due to an adverse event. No drug-related serious adverse events occurred., Conclusions and Relevance: Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering new nicotine dependence treatment options., Trial Registration: ClinicalTrials.gov Identifier: NCT04576949.

Background: Nicotine replacement therapy (NRT) has been demonstrated to be an effective pharmacological treatment for smoking cessation, and most types of NRT have been approved as over-the-counter (OTC) medications. In an effort to create a fast-acting, flexible, and discreet NRT, a nicotine mouth spray (NMS) has been developed. This study was designed to assess the efficacy and safety of NMS in a naturalistic setting in the United States., Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 26-week study in 1198 smokers motivated to quit. The study was designed to resemble an OTC environment, and thus included limited intervention, limited motivational screening, and no behavioral support. The primary efficacy endpoint was carbon monoxide-verified, self-reported continuous abstinence from smoking from week 2 until week 6. The safety of NMS was assessed by measuring vital signs, visual mouth inspection, and collection of subject-reported adverse events (AEs)., Results: The percentage of subjects with carbon monoxide-verified continuous abstinence from week 2 to week 6 was statistically significantly greater in the NMS group compared with the placebo group (5.0% vs. 2.5%, p = .021). Statistically significant treatment effects for the NMS were maintained throughout the 26-week period. The study medications were generally well tolerated. The severity of AEs was similar for both treatment groups, and most AEs were of mild or moderate severity., Conclusions: These study results demonstrate that the NMS is an effective and safe smoking cessation option for smokers motivated to quit, even in a naturalistic setting and without behavioral support., Implications: This study demonstrated the safety, efficacy, and acceptability of an NMS in an OTC environment with no behavioral counseling or support. It provides an additional option for smokers motivated to quit., Trial Registration: ClinicalTrials.gov (number NCT02355665)., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Objectives: To evaluate varenicline's efficacy for smoking cessation versus bupropion SR and placebo and to explore whether factors typically predictive of abstinence influence varenicline's efficacy versus placebo, as measured by the week 9-12 continuous abstinence rate (CAR9-12)., Methods: Smokers in 2 randomized, placebo-controlled trials received varenicline 1 mg BID (n=696), bupropion SR 150 mg BID (n=671), or placebo (n=685) for 12 weeks. Nontreatment followup lasted 40 weeks., Results: CAR(9-12) was greater for varenicline (44.0%) versus bupropion SR (29.7%; P<0.0001) and placebo (17.7%; P<0.0001). CAR(9-12) for varenicline versus placebo was not affected by age, gender, or nicotine dependence level., Conclusions: Varenicline was more efficacious than bupropion SR or placebo. Varenicline's efficacy versus placebo was not influenced by factors predictive of abstinence.

Although the proportion of the adult population in the United States that smokes has decreased steadily, the rate of successful quit attempts is still low. Smokers develop nicotine dependence that resembles other addictions, and may require multiple attempts and long-term treatment to sustain abstinence. Currently available first-line agents for smoking cessation therapy include nicotine replacement therapy, which is available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge; bupropion, an atypical antidepressant; and varenicline, a partial agonist of the alpha(4)beta(2) nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy. Second-line agents are nortriptyline, a tricyclic antidepressant agent, and clonidine, an antihypertensive drug. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. However, the adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. Rimonabant, a cannabinoid-1 receptor antagonist that was being developed for smoking cessation, received a nonapprovable letter from the FDA in 2006 and there is no further information as to whether development for this indication is continuing for this agent. Nicotine vaccines are under investigation and offer promise, especially for relapse prevention. Ultimately, selection of pharmacologic agent should be based on the patient's comorbidities and preferences, as well as on the agent's adverse event profile.

Objectives: To develop, implement, and assess the efficacy of a comprehensive, evidence-based smoking cessation program for entertainment industry workers and their families., Methods: Study participants were recruited from 5 outpatient medical clinics and a worksite setting. Tobacco use data were collected during the initial counseling visit and at 6-month follow-up. Univariate and multivariate regressions were used in analysis., Results: More than 50% of participants (n=470) self-reported 7-day abstinence at follow-up. The majority of participants used combination cessation medications, with more than 50% still using at least 1 medication at 6 months., Conclusions: This evidence-based smoking cessation program using behavioral counseling and combination pharmacotherapy was successful with entertainment industry workers.

Aims: To determine the efficacy and safety of nicotine transdermal therapy co-administered with the nicotine antagonist, mecamylamine, compared to a nicotine transdermal patch alone (21 mg nicotine + 6 mg mecamylamine, 21 mg nicotine + 3 mg mecamylamine, and 21 mg nicotine + 0 mg mecamylamine)., Design: Multi-center (n = 4), double-blind, randomized, parallel group, repeat-dose study., Setting: Clinical laboratory., Participants: A total of 540 subjects were enrolled into the study-135 from each of four sites; 180 patients in each of three treatment arms., Intervention: Treatment was administered for the first 6 weeks of the 8-week study. Patients were instructed to continue smoking for the first 2 weeks of treatment., Measurements: The primary efficacy parameter was 4-week continuous abstinence after the quit date, confirmed with an expired carbon monoxide of < 10 parts per million., Findings: Analysis of the 4-week continuous abstinence for the intent-to-treat population showed overall rates of 29% (nicotine + 6 mg mecamylamine), 29% (nicotine + 3 mg mecamylamine) and 23% (nicotine only) using the slip definition which allows smoking in the first 2 weeks after the quit date. Statistical analyses revealed no significant treatment differences. Analyses using the strict definition (no smoking after the quit date) yielded similar non-significant group differences (29%, 27%, 26%)., Conclusion: If adding mecamylamine to nicotine replacement therapy (NRT) improves the chances of success at stopping smoking, the results of this study suggest that the effect is very small.

Clinicians are in a unique position to reduce cardiovascular morbidity and mortality by helping their patients quit smoking. At each visit, clinicians should document smoking status, provide strong and clear advice to quit, and recommend and prescribe pharmacotherapy for patients who are motivated to quit, which can double the odds of success. Effective pharmacotherapies include nicotine replacement, bupropion, and varenicline, which was recently approved by the Food and Drug Administration. Behavioral counseling to develop a quit plan and extended follow-up are critical to maximize quit rates but are rarely provided by clinicians due to time constraints and lack of expertise. As an alternative, the authors recommend referral to telephone quitlines that provide no-cost behavioral counseling by specialists. Hospitals should implement systemwide procedures to ensure that smokers are identified at admission and trained staff is available to provide smoking cessation consults that include a minimum of 20 minutes of inpatient counseling with follow-up for at least 1 month.

Background: 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., Methods: 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., Results: 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., Conclusion: Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Context: 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., Objective: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo., Design, Setting, and Participants: 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., Intervention: 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., Main Outcome Measures: 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., Results: 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%])., Conclusion: 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., Trial Registration: clinicaltrials.gov Identifier: NCT00141206.

Aims: Most relapse episodes occur when smokers are confronted with craving provoked by situational cues. Current nicotine gum can help relieve cue-provoked cravings, but faster effects may result in more rapid relief. We tested a prototype formulation of a new rapid-release nicotine gum (RRNG) that provides more rapid release and absorption of nicotine, for its ability to provide faster and better craving relief compared to current nicotine polacrilex gum (NPG)., Design: Random assignment to RRNG or NPG, used during a smoking cue provocation procedure. Participants and setting A total of 319 smokers were exposed to a smoking cue in the laboratory by being asked to light but not smoke a cigarette of their preferred brand. Subjects then chewed a piece of 2 mg RRNG (n = 159) or 2 mg NPG (n = 160) according to randomized assignment., Measurements: Craving assessments were completed at regular intervals before and after cue exposure (baseline, pre-cue, and 3, 6, 9, 12, 15, 18, 21, 25, 30 and 35 minutes after the cue)., Findings: Smokers chewing RRNG showed significantly lower craving than NPG subjects starting with the first assessment at 3 minutes (P < 0.025). Repeated-measures ANOVA revealed a significant treatment x time interaction (P < 0.05)-craving scores dropped more rapidly in RRNG subjects compared to NPG subjects. Survival analyses also indicated superiority of RRNG in achieving more rapid self-reported meaningful relief (P < 0.05) and complete relief (P < 0.05) of craving., Conclusions: Rapid-release nicotine gum reduced cue-provoked craving more rapidly compared to NPG, and thus merits further study in cessation efficacy trials.

Previous findings from the Lung Health Study have shown that smoking cessation and sustained abstinence substantially reduce the rate of decline in forced expiratory volume (FEV(1)) among smokers with early chronic obstructive pulmonary disease (COPD) when compared with continuing smoking. Intermittent quitters demonstrated rates of FEV(1) decline intermediate between those of sustained quitters and continuing smokers. In this study, data from 1,980 participants were analysed from 10 centres of the Lung Health Study in the USA and Canada. All participants were smokers with mild-to-moderate COPD who were unable to quit smoking at any time during the 1st yr of the study. No linear relationship was found between reduction in cigarettes per day and changes in FEV(1) during the 1st yr of the study. However, examination of the data revealed that this relationship was nonlinear. Further analysis found that smokers who reduced their cigarettes per day to very low amounts had smaller declines in FEV(1) than those who did not. Reduction in cigarettes per day was associated with only minimal changes in the presence of chronic respiratory symptoms. In conclusion, compensatory changes in smoking behaviour may account for the limited and unpredictable impact of smoking reduction on lung function decline and symptom prevalence when compared with smoking cessation.

We examined the ability of smokers who failed to quit smoking in the Lung Health Study to reduce the number of cigarettes per day and maintain this reduction and whether reduction predicted increased or decreased future cessation. In the Lung Health Study, among smokers with early lung disease who wished to stop smoking, 3923 were randomized to a special intervention of counseling and nicotine gum for smoking cessation and to bronchodilator therapy or placebo. Among the 1722 who were still smoking at the first year follow-up, 27% smoked the same, 43% smoked 1%-49% fewer, and 30% smoked at least 50% fewer cigarettes per day. Reduction in cigarettes per day was accompanied by reduction in expired-air carbon monoxide. About half of the less-than-50% reducers and one-fifth of the at-least-50% reducers maintained or exceeded this reduction over the next 4 years. Reduction was associated with nicotine gum use. Greater reduction at year 1 predicted more quit attempts in year 2 but not more point prevalence abstinence at year 2 nor more quits or abstinence between years 2 and 5. We conclude that reduction can be maintained but such reduction neither predicts an increased nor decreased probability of future cessation.

Objective: To test initial reactions to 5 nicotine treatments (NRTs: 2 and 4 mg gum, inhaler, nasal spray, tablet) in a crossover study (n=41)., Methods: Subjects used each medication on arising (1/2 day) and resumed smoking each afternoon. Subjects rated (individually) and ranked (comparatively) treatments on use, reinforcement, withdrawal, craving, and preferences., Results: Overall preferences: inhaler (49%), 4 mg gum (24%), 2 mg gum (10%), 2 mg tablet (10%), nasal spray (7%). Overall results were consistent with ratings and rankings of individual characteristics of drugs., Conclusion: Subjects had varied reactions to NRTs that may affect initiation of cessation.

Background: Many persons who attempt to quit smoking have made previous unsuccessful attempts to quit with pharmacologic aids. An understanding of the impact of these previous attempts to quit is vital for selecting medications that may be more successful in a future attempt to quit. In particular, the effect of repeated use of bupropion SR (Zyban; INN, amfebutamone) on abstinence rates has not been studied previously., Methods: This was a multicenter, randomized, double-blind, placebo-controlled study in 450 smokers who had previously used bupropion in a smoking cessation attempt. The study consisted of a screening phase, a 12-week treatment phase, and a follow-up at month 6. Participants made regular clinic visits throughout the treatment phase during which they received brief counseling sessions to encourage abstinence from smoking. The primary end point was continuous abstinence from smoking from weeks 4 through 7. Secondary efficacy end points were examined throughout the treatment phase and at follow-up after 6 months., Results: In participants receiving bupropion SR, 27% (61 of 226) remained abstinent throughout the period from weeks 4 through 7 compared with 5% (11 of 224) of participants receiving placebo (P <.001). Significantly (P <.001) more participants who received bupropion SR during the treatment phase remained continuously abstinent from the start of week 4 through month 6 (27 of 226; 12%) compared with participants who received placebo (5 of 224; 2%). Eleven participants receiving placebo (5%) and 19 participants receiving bupropion SR (8%) stopped taking the study medication because of an adverse event., Conclusions: Bupropion SR is an effective medication for retreatment of smokers who have used bupropion SR previously.

Background: Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD., Methods: In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat., Findings: All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events., Interpretation: Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.

Objective: The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment., Methods: This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study., Results: The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo)., Conclusion: Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.

Objectives: The purpose of this study was to determine the efficacy and safety of the nicotine patch for smoking cessation in an over-the-counter environment. The years of study were 1994 to 1995., Methods: Parallel 6-week trials were conducted: a placebo-controlled trial of no-cost 22-mg, 24-hour nicotine patch therapy and an open label trial of the same therapy with patches purchased by subjects. Participants (n = 958) were 18 years or older, had smoked at least 15 cigarettes daily for at least 6 months, and were enrolled at 3 study sites. The main outcome measure was self-reported smoking abstinence confirmed by expired carbon monoxide measurements., Results: Smoking cessation rates in the placebo-controlled trial were 16.8% and 9.6% at week 6 and 8.7% and 4.3% at week 24 for the active patch and placebo groups, respectively. Smoking cessation rates in the open label-pay trial were 19.0% and 10.8% at weeks 6 and 24, respectively. A slight increase in adverse cardiovascular events was noted only in the open label-pay group in comparison with the placebo group., Conclusions: In an over-the-counter environment, the 22-mg, 24-hour nicotine patch is effective and safe for smoking cessation treatment.

Background and Methods: Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8., Results: The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache., Conclusions: Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.

The effect of intermittent smoking on pulmonary function was assessed among participants in the Lung Health Study, 5887 adult smokers with evidence of early chronic obstructive pulmonary disease (COPD), followed up for 5 years. The mean annual rate of loss in FEV1% of predicted after year 1 was smallest for those who quit at some point during the first year of the study and stayed quit (-0.33%/year, +/-0.05%), intermediate for those who smoked intermittently during the study (-0.58%/year, +/-0.05%) and greatest for those who continued to smoke throughout the study (-1.18%/year, +/-0.03%). Surprisingly, those who made several attempts to quit smoking had less loss of lung function at comparable cumulative doses of cigarettes than those who continued to smoke. Quitting smoking for an interval followed by relapse to smoking appeared to provide a measurable and lasting benefit in comparison to continuous smoking. In this early COPD population, not only quitting smoking but attempts to quit smoking can prevent some loss of lung function. These results provide some encouragement to exsmokers who relapse on their way to complete cessation.

The authors examine weight gains associated with smoking cessation in the Lung Health Study (1986-1994) over a 5-year follow-up period. A cohort of 5,887 male and female smokers in the United States and Canada, aged 35-60 years, were randomized to either smoking intervention or usual care. Among participants who achieved sustained quitting for 5 years, women gained a mean of 5.2 (standard error, 5.0) kg in year 1 and a mean of 3.4 (standard error, 5.5) kg in years 1-5. Men gained a mean of 4.9 (standard error, 4.9) kg in year 1 and a mean of 2.6 (standard error, 5.8) kg in years 1-5. In regression analyses, smoking-change variables were the most potent predictors of weight change. Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year (3.61%) in men and 3.09 kg/year (4.69%) in women. Over 5 years, 33% of sustained quitters gained > or = 10 kg compared with 6% of continuing smokers. Also among sustained quitters, 7.6% of men and 19.1% of women gained > or = 20% of baseline weight; 60% of the gain occurred in year 1, although significant weight gains continued through year 5. The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control.

Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group (N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 +/- 149 ng/ml) were similar to those in continuing smokers (290 +/- 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 +/- 276 ng/ml), NG-using smokers (309 +/- 240 ng/ml), and NG-non-using smokers (311 +/- 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.

The Lung Health Study enrolled 3,923 participants in a smoking cessation intervention program, and followed them for 5 years. The study provided intensive group interventions for participants who had relapsed. The purpose of this analysis was to describe and evaluate these Restart programs. Among 1,004 relapsed participants, the percent not smoking at 5th year was higher for men who had used Restart (47) compared to those who had not (28), but not for women (42 vs. 33). Overall, there was equivocal evidence of the impact of the Restart programs due to limitations in the evaluation design. Because relapse is a common feature of efforts to quit smoking, relapse intervention programs need further study and more rigorous evaluation.

Study Objective: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg., Design: A multicentered randomized control trial of early intervention for the prevention of COPD., Setting: Ten university medical centers in the United States and Canada., Participants: Adult smoking volunteers with evidence of early COPD; 3,923 in intervention and 1,964 controls., Intervention: Smoking cessation program, including NP., Measurements: Data on hospitalizations were collected annually. Data on reported NP side effects were collected at 4-month intervals for intervention participants., Results: The rates of hospitalization for cardiovascular conditions and cardiovascular deaths during the 5 years of the study were not related to use of NP, to dose of NP, or to concomitant use of NP and cigarettes. About 25% of NP users reported at least one side effect, but most were very minor and transient. Side effects associated with discontinuance of NP in 5% or more of users included headache, indigestion, mouth irritation, mouth ulcers, and nausea. There was no evidence that concomitant use of NP and cigarettes was associated with elevated rates of reported side effects. Participants in the smoking cessation intervention who received intensive levels of instruction and monitoring of NP use (initially at 12 meetings during 3 months) appeared to report significantly lower rates of side effects (dizziness, headache, and throat irritation) than control participants, presumed to have less instruction and monitoring., Conclusions: NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serous side effects.

Poor adherence to medication regimens is a well-documented phenomenon in clinical practice and an ever-present concern in clinical trials. Little is known about adherence to inhaled medication regimens over extended periods. The present paper describes the 2-yr results of the Lung Health Study (LHS) program, which was developed to maintain long-term adherence to an inhaled medication regimen in 3,923 special intervention participants (as measured by self-report and medication canister weight). The LHS is a double-blind, multicenter, randomized controlled clinical trial of smoking intervention and bronchodilator therapy (ipratropium bromide or placebo) for early intervention in chronic obstructive pulmonary disease (COPD). At the first 4-mo follow-up visit, nearly 70% of participants reported satisfactory or better adherence. Over the next 18 mo, self-reported satisfactory or better adherence declined to about 60%. Canister weight classified adherence as satisfactory or better in 72% of participants returning all canisters at 1 yr, and in 70% of the participants returning all canisters at the 2-yr follow-up. Self-reporting confirmed by canister weight classified 48% of participants at 1 yr as showing satisfactory or better adherence. Overusers were 50% more likely than others to misrepresent their true smoking status, suggesting that canister weights indicating overuse may be deceptive. Results of multiple logistic regression analysis indicate that the best compliance was found in participants who were married, older, white, had more severe airways obstruction, less shortness of breath, and fewer hospitalizations, and who had not been confined to bed for respiratory illnesses.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: An analysis of gender differences in smoking cessation was conducted among 3923 participants in the Special Intervention group of the Lung Health Study. This report focuses on gender differences in sustained quit rates at 12 and 36 months., Methods: Special Intervention participants were offered a 12-session, 12-week smoking cessation program using nicotine gum and were followed for 3 years. Self-reported smoking status was validated with carbon monoxide and salivary cotinine., Results: Men had higher sustained quit rates at 12 and 36 months; gender differences were found in baseline variables that also predicted sustained abstinence; and controlling for selected baseline variables reduced the association between gender and sustained abstinence. When other variables were controlled, gender predicted sustained abstinence at 36 months (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.04, 1.48) but not 12 months (OR = 1.08, 95% CI = 0.92, 1.27), reflecting more late relapse among women., Conclusions: Demographics and smoking history were more important than gender per se in sustained smoking cessation in the Lung Health Study. Programs tailoring smoking cessation by gender need to include coping skills for problems associated with less education and social support and for improving persistence with quit attempts.

Analyses were made separately for men and women of the predictors of end-of-treatment (4 months) smoking cessation and subsequent relapse at 12 and 24 months among 3,923 participants enrolled in the Lung Health Study's 12-week cognitive-behavioral group smoking cessation program. Nicotine gum (2 mg) was available to all participants. Men were more likely than women to quit smoking initially, but relapse rates were similar for both genders. Baseline variables associated with initial quitting for both genders included greater education, lower nicotine dependence, and fewer respiratory symptoms. The best predictor of relapse between 4 and 12 months was smoking at least 1 cigarette between quit day and 4 months. Nicotine gum use at 12 months predicted relapse by 24 months for both genders. Greater social and environmental support for quitting smoking were the only factors that predicted both initial quitting and relapse for both genders. Clinical implications are discussed.

The extent and predictors of weight change were assessed among sustained nonsmoking special intervention participants in the Lung Health Study. The intervention included a 12-session group program and 2-mg nicotine gum. At 12 months, female sustained quitters (SQs; n = 248) had gained a mean of 8.4% (5.3 kg) of their baseline weight, whereas male SQs (n = 443) had gained 6.7% (5.5 kg). By 24 months, female SQs had gained 9.8% of their baseline weight compared with 6.9% for men. Nicotine gum usage delayed a portion of the weight gain. Multiple regression analysis showed that weight gain at 12 months was associated with a higher baseline salivary cotinine level, a lower baseline body mass index, drinking less alcohol per week, and a lower cotinine level at 12 months (indicating less or no nicotine gum use). We conclude that moderate weight gain is a long-term consequence of smoking cessation--a portion of which can be delayed with 2-mg nicotine gum.

Of 3,923 special intervention participants in the Lung Health Study who were offered nicotine gum to help them quit smoking, 1,080 (28.9%) were using nicotine gum 12 months after entry into the study. This group is comprised of 33.6% sustained nonsmokers, 54.5% intermittent smokers, and 19.2% continuing smokers. The average use of gum at 12 months is 7.3 pieces per day. At 12 months, men were significantly more likely to be nonsmokers than women, but women were significantly more likely to use gum than men. Among the sustained nonsmokers, continuous gum users reported significantly more mild side effects than those who used gum intermittently, although there were no differences in moderate or severe side effects between the two groups. Overall, the rate of observed side effects was small. Factors associated with nicotine dependence were related to the use and amount of gum use at 12 months.

The Lung Health Study is a 10-center 5-year clinical trial sponsored by the National Heart, Lung, and Blood Institute to evaluate the effectiveness of early intervention in chronic obstructive pulmonary disease (COPD). The specific objectives of the trial are to determine whether the accelerated decline in lung function characteristic of COPD and morbidity due to COPD can be reduced by special intervention at a relatively early stage in the evolution of the disease. Special intervention consists of a smoking-cessation program and the use of an inhaled bronchodilator to suppress airway hyperreactivity. The use of the inhaler canister is monitored every 4 months by canister weighing and, at two of the 10 centers, by an electronic recording device, the Nebulizer Chronolog. Among trial participants assigned the latter device, results from the first 4 months of the study indicate that only 52% of trial participants who were uninformed as to the nature of the chronolog used their inhaler at least twice daily as measured by the chronolog, compared with 87% as determined by self-report. Satisfactory or good compliance was achieved by 52% of these subjects as measured by the chronolog compared with 85% as assessed by canister weighing. Eighteen percent of uninformed participants "dumped" their inhalers within a 3-hour time period, contributing to the inaccuracy of canister weights as an indicator of compliance. Feedback of information to the participants from the chronolog improved the level of compliance and eliminated the "dumping" phenomenon. We conclude that, when accurate determinations of compliance are important, as in a drug trial, objective medication monitors should be considered. Electronic monitoring of inhaler use can provide valuable feedback, which encourages improved compliance.