A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation

A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/-0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.     

Attitudes and knowledge about nicotine and nicotine replacement therapy.

Nicotine replacement therapies (NRTs) represent an effective means of promoting smoking cessation, but they remain underutilized. Negative attitudes and false beliefs about nicotine and nicotine replacement may cause NRT underutilization. In a randomized, controlled, single-blind study of nicotine gum, 97 smokers were assessed on their attitudes and knowledge about nicotine, nicotine replacement, and smoking cessation therapy. Information from these self-report measures was used in an intervention that provided tailored, brief feedback to promote positive attitudes and accurate knowledge about NRT. Considerable variability in pretreatment attitudes and knowledge was observed across individuals. Moreover, attitudes and knowledge showed a consistent pattern of intercorrelation and were systematically related to smoking characteristics (e.g., prior use of NRT, nicotine dependence, treatment completion). The brief feedback intervention led to a significant global elevation in attitudes about nicotine, NRT, and assisted cessation but not knowledge about nicotine. Changes in attitudes and knowledge were not significantly related to gum use or smoking cessation. Recommendations for the appropriate application of brief feedback are offered.     

The serotonin transporter 5-HTTLPR polymorphism and treatment response to nicotine patch: follow-up of a randomized controlled trial.

In this follow-up of a randomized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation, 741 smokers of European ancestry who were randomized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region. The study setting was a primary care research network in Oxfordshire, United Kingdom. The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up. The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment (SL: p=.33; SS: p=.81) or 24-week follow-up (SL: p=.05; SS: p=.21), and we found no evidence for a genotypextreatment interaction effect. In summary, despite the theoretically important contribution of serotonin neurotransmission to smoking cessation, the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial.     

Characteristics of selectors of nicotine replacement therapy

Objective: To assess differences in demographic and smoking characteristics between smokers who have and have not used nicotine replacement therapy (NRT). Design: Mail survey of US smokers from a national research panel. Participants: Smokers 18 years and over who returned a survey on smoking (n = 9630). The sample was weighted to match the US smoker population on age and sex. Main outcome measures: Compared smokers who had/had not used NRT in a quit attempt (ever NRT use or over the counter (OTC) NRT use) on: demographic characteristics, nicotine dependence, history of craving and withdrawal, expected difficulty quitting, and self reported history of smoking related medical illness and psychopathology. Results: NRT users (both ever-users and OTC users) were more likely to be older, male, and better educated. They were also heavier smokers, had experienced more craving and withdrawal upon quitting, and scored higher on measures of dependence. These differences were evident among light smokers, and remained even when smoking rate and time to first cigarette were controlled. Conclusion: Smokers who elect to use NRT differ from non-NRT users in ways that predispose them to failure in cessation. Controlling for smoking rate and time to first cigarette does not eliminate these differences, even among light smokers. These differences must be considered when comparing the effectiveness of NRT among samples of smokers who self select their treatment and are likely to bias such outcome comparisons.     

Interest in gradual cessation.

Prior surveys have not determined smokers' interest in gradual cessation. In Study 1A, we advertised in six U.S. east coast newspapers for "smokers who plan to quit smoking" to participate in a nontreatment study. Among the 461 respondents, 66% planned to reduce and then stop smoking, 13% planned to stop abruptly, and 21% reported they planned to reduce but not quit. In Study 1B, we ran a similar ad but asked for "smokers who plan to reduce their smoking." Among the 263 respondents, 57% planned to reduce and then stop smoking and 33% planned to reduce but not stop smoking. In Study 2, we asked 125 smokers to rate their interest in quitting smoking (on a 1-10 scale) given two scenarios. When nicotine replacement therapy (NRT) was not mentioned, interest in gradual cessation was high and was higher than interest in abrupt cessation (6.9 and 4.7, respectively, p<.0001). When NRT was assumed to be available for gradual or abrupt cessation, interest in gradual cessation remained high (7.1) and was similar to that for abrupt cessation (7.0). In both scenarios, over three-fourths of smokers were at least as interested in gradual cessation as they were in abrupt cessation.     

Randomized trial of a smoking cessation intervention in hospitalized patients

A hospitalization is a time when perceived vulnerability to dangers from smoking and quitting motivation may be at their peak. Aim was to determine whether a smoking cessation intervention of moderate intensity would increase the smoking cessation rate in hospitalized smokers. Design was randomized trial, conducted in a university-affiliated cardio-pulmonary tertiary care center. Participants were hospitalized smokers aged < or =70 years. Intervention was a smoking cessation intervention consisting of education and psychological support, with or without pharmacological therapy, associated with follow-up phone calls. Patients assigned to the control group received usual care. Measurement was point prevalence cessation rate at 1-year follow-up. A total of 468 patients were screened; 196 were randomized. Although the smoking cessation rates at 12-month follow-up were higher than expected, we found no significant difference between the study groups (intervention: 30.3%; control: 27.8%). Similar results were obtained in patients whose smoking status was validated by urinary cotinine assay. Length of stay and dependence to nicotine were the only significant predictors of smoking cessation. A smoking cessation intervention of moderate intensity delivered in a tertiary cardio-pulmonary center did not increase the smoking cessation rate at 1-year follow-up. The results of this trial should not divert those who deliver care to inpatients from delivering a brief smoking cessation intervention.     

Transdermal nicotine use in postmenopausal women: does the treatment efficacy differ in women using and not using hormone replacement therapy?

This study of postmenopausal female smokers (N = 94) asked: During short-term smoking abstinence, do the beneficial effects of transdermal nicotine replacement therapy (NRT) on acute symptomatology (i.e., withdrawal, cigarette craving, smoking urges, mood, depressive symptoms, motor speed, and reaction time) differ in women who use and do not use hormone replacement therapy (HRT)? Participants were recruited according to HRT and non-HRT use (self-selecting), then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking.     

Predictors of smoking cessation among elderly smokers treated for nicotine dependence

OBJECTIVE: To examine outcomes and predictors of smoking cessation among elderly patients treated for nicotine dependence. DESIGN: Retrospective analysis of patients aged 65-82 who received a nicotine dependence consultation at the Mayo Medical Center between 1 April 1988 and 30 May 1992. Patients were contacted by telephone by a trained interviewer six months after the consultation and were sent a follow-up survey in August 1993. SETTING: Mayo Medical Center, Rochester, Minnesota, United States. SUBJECTS: A total of 613 patients (310 men, 303 women) with a mean age of 69.0 (SD 3.5) years were seen during the study period. MAIN OUTCOME MEASURES: Point prevalence self-reported smoking status. Patients were considered abstinent if they self- reported not smoking (not even a puff) during the seven days before contact. RESULTS: At six-month follow up, 24.8% of the 613 patients reported abstinence from smoking. On multivariate analysis, smoking abstinence was more likely if patients were hospitalised at the time of the consultation, married to a non-smoking spouse, very motivated to stop smoking, and reported their longest time of previous abstinence to be less than a day or more than a month. The response rate to the mailed follow-up survey was 69.9% (429 of 613). The mean duration of follow up was 40.0 +/- 13.2 months following the consultation. Of the 429 patients, 103 (24.0%) reported abstinence from smoking and 326 (76.0%) were smoking at six-month follow up. Patients who reported abstinence at six months had a higher cessation rate at the last follow up (76.0%) compared with patients who were smoking at six-month follow up (33.0%, P < 0.001). For patients who were not smoking at six months, no factors were found to significantly predict abstinence at last follow up. For patients who were smoking at six months, factors associated with smoking cessation at last follow up were: more than a year as the longest time off cigarettes before the consultation; counsellor rating of less severe nicotine dependence; and older age at first regular smoking. CONCLUSIONS: Several predictors of smoking cessation were identified in this study which may be useful for tailoring smoking interventions for the elderly.


     

Designing smoking cessation services for school-age smokers: A survey and qualitative study.

To identify the preferred design characteristics of smoking cessation services for school-age smokers, we conducted focus groups with teenage smokers motivated to stop smoking. We surveyed all pupils in years 9-11 (aged 13-16) in a random sample of 10 schools in Nottinghamshire, United Kingdom, to elicit details of smoking behavior, and conducted 25 focus groups in 6 schools with current smokers who wanted to stop smoking. Of 4,065 pupils surveyed, 888 (22%) were current smokers, and 438 (50% of smokers) wanted to quit smoking. We sampled 226 of these individuals for focus group studies, and 135 (60%) participated. These participants were motivated to quit, and almost all had tried to do so but had found it too difficult. Many were aware of smoking cessation methods but had low perceptions of their effectiveness based on their own or others' poor experiences of these interventions, and few were aware of the possibility of professional cessation support. Given clear, nondirective information about interventions, participants reported a preference for confidential, nonjudgmental services delivered during school time by a trained counselor, allowed the option to attend with friends, and offered nicotine replacement therapy (NRT). School-age smokers in Nottinghamshire, United Kingdom, who are motivated to stop smoking have low knowledge and opinions of smoking cessation interventions. Our findings indicate that young smokers would favor school-based services offering confidential professional counseling and NRT.     

Smoking cessation patterns in methadone-maintained smokers.

To determine predictors of smoking cessation duration in a randomized clinical trial, we assigned participants to nicotine patch (8-12 weeks) plus either (a) a baseline tailored brief motivational intervention, a quit date behavioral skills counseling session, and a relapse prevention follow-up session, or (b) brief advice using the National Cancer Institute's 4A's model. A total of 383 smokers from five methadone maintenance treatment centers in Rhode Island were enrolled, of whom 312 (82%) completed 6-month follow-up assessments. The primary outcome was longest period of self-reported abstinence during follow-up. Participants were on average 40.5 years of age; 51.9% were male, and 77.6% were White. In multivariate analysis controlling for demographics, nicotine dependence, depressive symptoms, and smoking-related symptoms, we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline (OR = 1.97, p = .003), in those anticipating success in cessation (OR = 1.33, p = .024), and in those with a greater percentage of nicotine patch use days (OR = 2.78, p<.001). Past quit attempts, self-efficacy, and constant nicotine replacement were associated with duration of abstinence among methadone-maintained smokers. Attention to these domains in future intervention studies may improve treatment success.     

Smokers' interest in using nicotine replacement to aid smoking reduction.

In recent years the public health community has considered the risks and benefits of encouraging smokers to reduce their smoking, perhaps with the aid of nicotine replacement therapy (NRT). Little is known, however, about whether smokers themselves are interested in smoking reduction; whether they see reduction as an endpoint, or primarily as a route to cessation; or whether they are receptive to the notion of using NRT to achieve reduction. We conducted a population-based national telephone survey of 1,000 current daily cigarette smokers (499 male, 501 female). Most smokers (57%) reported previously trying to reduce their smoking, and many (26%) said that they plan to reduce within the next year. Almost half of those planning to quit in the next 12 months (44%) preferred to quit via gradual cessation and most (68%) indicated that they would consider using a reduction product or medication. Respondents reported that they would prefer a product with a cessation endpoint rather than a reduction endpoint (63% vs. 21%). Interest in reduction was highest among smokers who were less interested in quitting and among heavier smokers. We conclude that many smokers are interested in gradually reducing prior to quitting and that promoting reduction is unlikely to undermine motivation to quit smoking.     

The impact of carotid plaque screening on motivation for smoking cessation.

Showing smokers their own atherosclerotic plaques might increase motivation for smoking cessation, since they underestimate their own risk for smoking-related diseases. To assess the feasibility and optimal processes of studying the impact of carotid atherosclerotic plaque screening in smokers, we enrolled 30 daily cigarette smokers, aged 40-70 years, in an observational pre-post pilot study. All smokers underwent smoking cessation counseling, nicotine replacement therapy, a carotid ultrasound, an educational tutorial on atherosclerosis, baseline and 2-month motivation to change assessment, and assessment of smoking cessation at 2 months. Participants had a mean smoking duration of 34 years (SD = 7). Carotid plaques were present in 22 smokers (73%). Between baseline and 2 months after plaque screening, motivation for smoking cessation increased from 7.4 to 8.4 out of 10 (p = .02), particularly in those with plaques (7.2 to 8.7, p = .008). At 2 months, the smoking quit rate was 63%, with a quit rate of 73% in those with plaques vs. 38% in those without plaques (p = .10). Perceived stress, anxiety, and depression did not increase after screening. 96% of respondents answered correctly at least 80% of questions regarding atherosclerosis knowledge at baseline and after 2 months. In conclusion, studying the process of screening for carotid plaques for the purpose of increasing motivation for smoking cessation, in addition to counseling and drug therapy for smoking cessation in long-term smokers, appears feasible. The impact of carotid plaque screening on smoking cessation should be examined in larger randomized controlled trials with sufficient power to assess the impact on long-term smoking cessation rates.     

Use of nicotine replacement therapy to reduce or delay smoking but not to quit: prevalence and association with subsequent cessation efforts

Objective

To assess the prevalence of nicotine replacement therapy (NRT) use for purposes other than quitting smoking and examine the relation of this non‐standard NRT use (NSNRT) with subsequent smoking cessation efforts.

Design

A population based cohort study of adult smokers who were interviewed by telephone at baseline (2001–2) and at two year follow‐up. The association between NSNRT use to cut down on smoking or to delay smoking before baseline and cessation attempts and smoking outcomes at two year follow‐up was assessed using logistic regression to adjust for multiple potential confounding factors.

Setting

Massachusetts, USA.

Subjects

1712 adult smokers in Massachusetts who were selected using a random digit dial telephone survey.

Main outcome measures

Quit attempt in 12 months before follow‐up, NRT use at quit attempt in 12 months before follow‐up, smoking cessation by follow‐up, or 50% reduction in cigarettes smoked per day between baseline and follow‐up.

Results

18.7% of respondents reported ever having used NSNRT. In a multiple logistic regression analysis, there was no statistically significant association between past NSNRT use and quit attempts (OR_{cut down}  = 0.89, 95% CI 0.59 to 1.33; OR_delay  = 1.29, 95% CI 0.73 to 2.29), smoking cessation (OR_{cut down}  = 0.74, 95% CI 0.43 to 1.24; OR_delay  = 1.22, 95% CI 0.60 to 2.50) or 50% reduction in cigarettes smoked per day (OR_{cut down}  = 0.93, 95% CI 0.62 to 1.38; OR_delay  = 0.80, 95% CI 0.43 to 1.49) at follow‐up. Past use of NRT to cut down on cigarettes was associated with use of NRT at a follow‐up quit attempt (OR_{cut down}  = 2.28, 95% CI 1.50 to 3.47) but past use of NRT to delay smoking was not (OR_delay  = 1.25, 95% CI 0.67 to 2.34).

Conclusions

Use of NRT for reasons other than quitting smoking may be more common than was previously estimated. This population based survey finds no strong evidence that NRT use for purposes other than quitting smoking is either harmful or helpful.     

Nicotine replacement therapy, professional therapy, snuff use and tobacco smoking: a study of smoking cessation strategies in southern Sweden

Objectives

The strategies used to support smoking cessation among quitters were investigated according to year of smoking cessation and sociodemographic characteristics.

Methods

The 2004 public health survey in Skåne, Sweden, is a cross‐sectional study. A total of 27 757 people aged 18–80 answered a postal questionnaire. The participation rate was 59%. Different strategies to support smoking cessation—that is, no therapy, nicotine replacement (NRT), professional therapy and snus (snuff) use, were investigated among quitters according to year of smoking cessation, and demographic and socioeconomic characteristics.

Results

14.9% of the men and 18.1% of the women were daily smokers. The prevalence of daily snus use was 19.5% among men but only 2.3% among women. Stratifying the data according to year of smoking cessation (1938–2004) revealed a significant increase in active smoking cessation strategies such as NRT, professional therapy and snus use. NRT was more common among women (23.6%) than men (14.8%) among smokers who quit in 2000–4, but snus use was more common among men (30.4% versus 8.7%). No replacement or other therapy at all was significantly more common among women (63.6%) than men (52.1%). People aged 35–80 years used more nicotine replacement than people aged 18–34, while men aged 18–34 used snus to quit smoking significantly more than men aged 55–80.

Conclusions

Snus is used commonly among men as a support for smoking cessation in Sweden. Women use pharmacological NRT to a greater extent, but this can probably not compensate for the much higher extent of snuff use as a cessation strategy among men.     

Over-the-counter availability of nicotine replacement therapy and smoking cessation.

In 1996, the FDA approved over-the-counter (OTC) availability of nicotine gum and two brands of nicotine skin patches. Little is known about how this reclassification has influenced the effectiveness and use of nicotine replacement therapy (NRT) and whether it has been a public health benefit. Data for the present study came from a prospective cohort study of 1,639 adult smokers surveyed by telephone in 1993, as part of the National Cancer Institute's Community Intervention Trial for Smoking Cessation (COMMIT), and resurveyed in 2001. NRT-assisted quit rates, NRT use rates, and the characteristics of NRT users were calculated before and after the 1996 OTC reclassification. Also calculated was the percentage of NRT users who quit by year. Results are presented for patch and gum separately and combined. OTC NRT use rates were lower for Hispanics and higher for those with no desire to quit at baseline. The quit rate decreased for patch-assisted quit attempts after OTC reclassification (22.5% to 18.5%, p = .05), but it did not change for gum-assisted quit attempts (11.9% to 10.5%, p = .54). NRT use rates increased for both patch and gum by about 60% following reclassification. A greater percentage of gum users had quit in the post-OTC period than in the pre-OTC period (9.7% vs. 14.6%, p = .05). Long-term quit rates in patch users were similar in both periods. Insurance coverage of NRT and concurrent attendance in a stop smoking clinic decreased for both patch- and gum-assisted attempts in the post-OTC period. The results suggest that OTC reclassification may have contributed to the increased use of NRT, compared with the pre-OTC period, whereas the efficacy for quitting decreased slightly for those using nicotine patch and remained about the same for those using the gum.     

Is Swedish snus associated with smoking initiation or smoking cessation?

Nicotine replacement therapies (NRT) are an effective treatment for tobacco dependence, yet most smokers do not quit or remain abstinent. We investigated whether Swedish snus (snuff) use was associated with smoking cessation among males participating in a large population based twin study in Sweden. Snus use was associated with smoking cessation but not initiation. Given that snus delivers comparable nicotine concentrations but carries lesser cancer risk than cigarettes, snus may be a widely used, non-medical form of NRT. Evaluation of the efficacy of snus for smoking cessation should be evaluated in randomised clinical trials.