Nortriptyline for smoking cessation: a review.

This article reviews the efficacy of nortriptyline for smoking cessation based on a meta-analysis of the Cochrane Library. Six placebo-controlled trials have shown nortriptyline (75-100 mg) doubles quit rates (OR = 2.1). Between 4% and 12% of smokers dropped out because of adverse events, but no serious adverse events occurred. The efficacy of nortriptyline did not appear to be related to its antidepressant actions. Nortriptyline is an efficacious aid to smoking cessation with a magnitude of effect similar to that for bupropion and nicotine replacement therapies. Whether nortriptyline produces serious side effects at these doses in healthy, nondepressed smokers remains unclear because it has been tested in only 500 smokers. The finding that nortriptyline and bupropion are effective for smoking cessation but that selective serotonin-reuptake inhibitors are not suggests that dopaminergic or adrenergic, but not serotonergic, activity is important for cessation efficacy. Until further studies can verify a low incidence of significant adverse events, nortriptyline should be a second-line treatment for smoking cessation.     

Teen smoking cessation

Interest in adolescent smoking cessation has increased dramatically over the past several years, as researchers and practitioners have acknowledged the high rates of adolescents who smoke regularly and the low probability that adolescents who are regular smokers will stop on their own. The evidence base behind smoking cessation interventions for adolescents is also now starting to grow, but unfortunately the studies to date have frequently been plagued by major methodological problems. This paper summarises research conducted on adolescent smoking cessation, notes some of the methodological limitations of prior work, highlights approaches that show promise, discusses some of the challenges involved in addressing adolescent smoking cessation, and makes recommendations for future work.     

Bupropion and cognitive-behavioral treatment for depression in smoking cessation.

This study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment (CBTD) and of bupropion, both singularly and in combination, on smoking cessation in adult smokers. As an extension of our previous work, we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors. Participants were 524 smokers (47.5% female, M (age) = 44.27 years) who were randomized to one of four 12-week treatments: (a) standard, cognitive-behavioral smoking cessation treatment (ST) plus bupropion (BUP), (b) ST plus placebo (PLAC), (c) standard cessation treatment combined with cognitive-behavioral treatment for depression (CBTD) plus BUP, and (d) CBTD plus PLAC. Follow-up assessments were conducted 2, 6, and 12 months after treatment, and self-reported abstinence was verified biochemically. Consistent with previous studies, bupropion, in comparison with placebo, resulted in better smoking outcomes in both intensive group treatments. Adding CBTD to standard intensive group treatment did not result in improved smoking cessation outcomes. In addition, neither CBTD nor bupropion, either alone or in combination, was differentially effective for smokers with single-past-episode major depressive disorder (MDD), recurrent MDD, or elevated depressive symptoms. However, findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample. An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials.     

Bupropion and cognitive-behavioral therapy for smoking cessation in women.

Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women. It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered. This study used a two level factorial design to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]). In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments, we examined medication compliance and its role in the efficacy of bupropion. Participants were 154 women, aged at least 30 years and smoking more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-, 9-, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women.     

Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation.

This randomized, double-blinded, placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation. Smokers of European ancestry (N = 291), who were randomized to receive bupropion or placebo (12 weeks) plus counseling, were genotyped for the dopamine D2 receptor (DRD2-Taq1A), dopamine transporter (SLC6A3 3' VNTR), and cytochrome P450 2B6 (CYP2B6 1459 CT) polymorphisms. Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2-, 6-, and 12-month follow-ups post quit date. Using generalized estimating equations, we found that bupropion, compared with placebo, was associated with significantly greater odds of abstinence at all time points (all p values<.01). We found a significant DRD2 x bupropion interaction (B = 1.49, SE = 0.59, p = .012) [corrected] and a three-way DRD2 x bupropion x craving interaction on 6-month smoking cessation outcomes (B = -0.45, SE = 0.22, p = .038), such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion. Furthermore, there was a significant DRD2 x CYP2B6 interaction (B = 1.43, SE = 0.56, p = .01), such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype. Because the sample size of this study was modest for pharmacogenetic investigations, the results should be interpreted with caution. Although these results require replication, the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and, further, that exploration of gene x gene and gene x craving interactions in future, larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion.     

Dimensions of depressive symptoms and smoking cessation.

Because different psychopathologic components of depressive symptoms may have distinct etiologies, examining their differential effects on smoking cessation may elucidate mechanisms underlying the smoking-depression relationship. Negative affect (NA), somatic features (SF), low positive affect/anhedonia (PA), and interpersonal disturbance (IP) have been identified as unique dimensions of depression that can be measured using the Center for Epidemiologic Studies Depression Scale (CESD). This study examined common and unique associations between CESD subscales and baseline smoking characteristics, nicotine withdrawal, and relapse in 157 participants enrolled in a smoking cessation trial for heavy social drinkers. Each dimension was univariately associated with negative and positive reinforcement smoking motives. Only SF had unique relations with tolerance smoking motives and univariate associations with nicotine dependence severity. Only PA predicted cessation-related changes in withdrawal symptoms on quit day. Analyses predicting abstinence at 8, 16, and 26 weeks post quit date showed that NA, SF, and PA each univariately predicted relapse, ps< or =.0083. Only low PA predicted poorer outcomes incrementally to the other dimensions, even when controlling for level of nicotine dependence, smoking frequency, and history of major depression, p = .0018. Interventions targeting anhedonia and low positive affect may be useful for smokers trying to quit.     

Gabapentin for smoking cessation: a preliminary investigation of efficacy.

Gabapentin affects the glutamate and gamma amino butyric acid (GABA) neurotransmitters through which it may facilitate smoking abstinence. To obtain preliminary estimates of efficacy of gabapentin for smoking cessation, we conducted a single-arm, open-label study of gabapentin, 1,800-mg/day administered in three equal divided doses for 8 weeks. A total of 50 adult smokers were enrolled. All participants received a brief behavioral intervention at each medication visit. A total of 37 participants completed all follow-up assessments. At end-of-treatment the biochemically confirmed point-prevalence and prolonged smoking abstinence rates were 28% (95% CI=16%-42%) and 24% (95% CI=13%-38%), respectively. At 6 months, the biochemically confirmed point-prevalence and prolonged smoking abstinence rates were 20% (95% CI=10%-34%) and 16% (95% CI=7%-29%), respectively. Among subjects who continued to smoke and completed the follow-up assessments, the reported number of cigarettes smoked per day (mean+/-standard deviation) was significantly less than at baseline: -10.0+/-8.2 (p<.001). Adverse effects were minor and well tolerated. Our results suggest that gabapentin may increase smoking abstinence. An adequately powered randomized clinical trial assessing different doses of this drug against a placebo would be the reasonable next step.     

Parental smoking cessation and children's smoking: mediation by antismoking actions.

The present study investigated whether parents' antismoking actions mediated the prospective relationship between parental smoking cessation and children's smoking. Smoking status of parents (predictor) was assessed when their children were in 3rd grade, parental antismoking actions (mediators) were assessed when their children were in 11th grade, and children's smoking status (outcome) was assessed when they were in 12th grade. In 20 Washington state school districts, data were collected from 1,600 children (49% female, 91% White) and from their parents. Results showed that children's odds of daily smoking were reduced by 39% (95% CI = 24%-51%) for those whose parents had quit smoking, compared with those whose parents were current smokers. Asking to sit in nonsmoking sections of public establishments was a significant (p<.01) mediator that explained 64% of the association between parental smoking cessation and children's smoking. However, not allowing smoking in the home and asking others not to smoke around them were not significant mediators (p = .10, and p = .06, respectively). In conclusion, asking to sit in a nonsmoking section of a public establishment substantially mediates the relationship between parental smoking cessation and children's smoking.     

Telephone booster sessions for optimizing smoking cessation for patients in rehabilitation centers.

Smokers with smoking-related diseases who are hospitalized in rehabilitation centers should be offered smoking cessation. This is the first study evaluating whether telephone booster sessions after intensive inpatient treatment are an effective strategy. The present study was conducted in 13 rehabilitation centers for somatic disorders as a prospective multicenter study with a randomized treatment-control group design. We compared abstinence rates after hospital discharge from treatment that included a group smoking cessation program with (treatment group) and without telephone booster sessions (control group). Data from 290 smokers were analyzed. After 6 and 12 months the treatment group achieved abstinence rates twice as high as those of the control group. Men profited more from telephone booster sessions than did women. Results indicated that telephone booster sessions were highly effective (even) after an inherently intensive group program during a hospital stay. Further research should focus on the special needs of women receiving telephone counseling.     

Hypnosis for smoking cessation: a randomized trial

The purpose of this study was to determine whether hypnosis would be more effective in helping smokers quit than standard behavioral counseling when both interventions are combined with nicotine patches (NP). A total of 286 current smokers were enrolled in a randomized controlled smoking cessation trial at the San Francisco Veterans Affairs Medical Center. Participants in both treatment conditions were seen for two 60-min sessions, and received three follow-up phone calls and 2 months of NP. At 6 months, 29% of the hypnosis group reported 7-day point-prevalence abstinence compared with 23% of the behavioral counseling group (relative risk [RR] = 1.27; 95% confidence interval, CI 0.84-1.92). Based on biochemical or proxy confirmation, 26% of the participants in the hypnosis group were abstinent at 6 months compared with 18% of the behavioral group (RR = 1.44; 95% CI 0.91-2.30). At 12 months, the self-reported 7-day point-prevalence quit rate was 24% for the hypnosis group and 16% for the behavioral group (RR = 1.47; 95% CI 0.90-2.40). Based on biochemical or proxy confirmation, 20% of the participants in the hypnosis group were abstinent at 12 months compared with 14% of the behavioral group (RR = 1.40; 95% CI 0.81-2.42). Among participants with a history of depression, hypnosis yielded significantly higher validated point-prevalence quit rates at 6 and 12 months than standard treatment. It was concluded that hypnosis combined with NP compares favorably with standard behavioral counseling in generating long-term quit rates.     

A meta-analysis of acupuncture techniques for smoking cessation

OBJECTIVE: To determine the effectiveness of acupuncture for smoking cessation and to examine whether any individual aspect of trials is associated with an effect. DATA SOURCES: All randomised controlled trials of acupuncture for smoking cessation that were listed in computerised databases or reference lists of relevant articles. STUDY SELECTION: All randomised single-blind studies that compared acupuncture with sham acupuncture. DATA EXTRACTION: Methodological data were extracted for quality assessment. Outcome data were extracted for rates of total smoking cessation at three intervals: early after treatment and after six and 12 months follow up. DATA SYNTHESIS: Results were expressed as odds ratios of success over failure in intervention over control groups. The combined odds ratio for all studies was calculated. Repeated meta-analyses were subsequently performed on subsets of studies combined according to defined characteristics: acupuncture technique, number of attendances, country of origin, status of journal, and control procedure. The overall quality of studies was poor. The combined odds ratio for smoking cessation calculated for the earliest results after the end of treatment was 1.20 (95% confidence intervals (95% CIs) = 0.98 to 1.48). The combined odds ratio for smoking cessation after six months was 1.29 (95% CI = 0.82 to 2.01), and after 12 months was 1.03 (95% CI = 0.73 to 1.46). There were no significant effects of relevance among subsets of studies grouped according to defined characteristics. CONCLUSIONS: Acupuncture was not superior to sham acupuncture for smoking cessation; no particular aspect of acupuncture technique was associated with a positive effect. The conclusions are limited by methodological inadequacies of studies and by the absence of testable hypotheses; design of future trials should avoid these deficiencies.     

The relationship between smoking cessation and mouth ulcers.

Patients who stop smoking often complain of aphthous (mouth) ulcers. This symptom is sometimes attributed to the use of smoking cessation medications, but little is known about it. We investigated the incidence, severity, and time course of mouth ulcers in abstaining smokers and the effect of different smoking cessation medications on the symptom. The sample consisted of 1234 smokers who sought treatment at a large smoking cessation clinic, maintained at least 1 week of continuous biochemically validated abstinence, and provided usable data. Participants assessed their mouth ulcers by rating a mouth ulcer item added to the Mood and Physical Symptoms Scale. Subjects made ratings weekly on three occasions while still smoking and over 4 weeks following smoking cessation. After stopping smoking, some 40% of patients developed mouth ulcers, mostly in the first 2 weeks. The problem was generally mild, but 8% reported severe ulceration. The ulcers resolved within 4 weeks in 60% of patients affected. The ulcer ratings in patients using oral nicotine replacement products were higher than in those using patch, nasal spray or bupropion in the first week of abstinence but not afterward. Mouth ulcers were more prevalent in more dependent smokers, and the occurrence of ulcers correlated with other tobacco withdrawal symptoms. Our results confirm that mouth ulcers are a common result of stopping smoking, affecting two in five quitters. Patients should be reassured that the lesions are a result of stopping smoking and not a side-effect of smoking cessation medication.     

Effects of smoking cessation and reduction in asthmatics.

The present study examined the effect of smoking reduction and cessation on asthma regulation and biomarkers of exposure to cigarette smoke. In a prospective open design, we allocated 220 asthmatics among three groups: (a) Smoking reduction (reducers), with the aim of smoking fewer than seven cigarettes per day, (b) complete smoking cessation (abstainers), or (c) continuation of usual smoking (continuing smokers). Subjects used nicotine chewing gum or an oral nicotine inhaler to promote reduction and cessation. We monitored changes in the biomarkers carbon monoxide, cotinine, and thiocyanate, and in peak flow, medicine use, bronchial reactivity, and asthma symptoms. The analysis used the three outcome groups, regardless of original allocation to treatment groups. At 4 months, analysis of abstainers (n = 27), reducers (n = 33), and continuing smokers (n = 50) showed marked, statistically significant decreases in expired carbon monoxide of 17 ppm (abstainers) and 15 ppm (reducers); in plasma cotinine of 124 ng/ml (abstainers) and 122 ng/ml (reducers); and in plasma thiocyanate of 5.03 ng/ml (abstainers) and 3.74 ng/m (reducers). For abstainers, we observed improvements in the asthma-specific quality-of-life score, and reductions in self-reported day and night use of rescue beta2-agonists, in doses of inhaled corticosteroids, in daytime asthma symptoms, and in bronchial hyperreactivity. For reducers, smaller improvements occurred for night use of rescue beta2-agonists, doses of inhaled corticosteroids, and bronchial hyperreactivity. Smoking cessation resulted in a marked decrease in three biomarkers of cigarette smoke inhalation and improved asthma regulation, whereas smoking reduction had a less pronounced effect on biomarkers and only a small effect on asthma regulation.     

Social class, education, and smoking cessation: Long-term follow-up of patients treated at a smoking cessation unit.

Our objective was to examine social class and educational differences in long-term smoking cessation success among a cohort of smokers attending a specialized smoking clinic. We studied sustained abstinence after cessation among 1,516 smokers (895 men and 621 women) treated for smoking cessation between 1995 and 2001 at a university teaching hospital in the metropolitan area of Barcelona, Spain. We calculated 1-year and long-term (up to 8-year) abstinence probabilities by means of Kaplan-Meier curves and the hazard ratio of relapse by means of Cox regression, after adjusting for other predictors of relapse. Overall abstinence probability was .277 (95% CI = .254-.301). Men and women in social classes IV-V had significant hazard ratios of relapse after long-term follow-up (men: 1.36, 95% CI = 1.07-1.72; women: 1.60, 95% CI = 1.24-2.06), as compared with patients in social classes I-II. The same independent effect was observed for education: Men and women with primary or less than primary studies had higher hazard ratios of relapse (men: 1.75, 95% CI = 1.35-2.25; women: 1.92, 95% CI = 1.51-2.46), as compared with patients with a university degree. Similar estimates were obtained after adjustment for stage of change, Fagerstr?m score for nicotine dependence, and type of treatment. Patients of lower socioeconomic status are at higher risk of relapse, and this association is independent of other well-known predictors of relapse. Social differences have to be taken into account in the clinical setting when tailoring specific actions to treat smoking dependence.     

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.     

Support for spirituality in smoking cessation: results of pilot survey.

Patient spiritual resources are increasingly included in the treatment of medical conditions such as cancers and alcohol and drug dependence, but use of spiritual resources is usually excluded from tobacco dependence treatment. We hypothesized that this omission may be linked to perceived resistance from smokers. To examine this hypothesis, we conducted a pilot survey to assess whether current smokers would consider spiritual, including religious, resources helpful if they were planning to quit. Smokers at least 18 years of age at Oregon Health & Science University in Portland, Oregon, (N=104) completed a brief survey of smoking behaviors and spiritual beliefs. None were attempting to quit. Of these individuals, 92 (88%) reported some history of spiritual resources (spiritual practice or belief in a Higher Power), and of those respondents, 78% reported that using spiritual resources to quit could be helpful, and 77% reported being open to having their providers encourage use of spiritual resources when quitting. Results of logistic regression analysis indicated that those aged 31-50 years (OR=3.3), those over age 50 years (OR=5.4), and women (OR=3.4) were significantly more likely to have used spiritual resources in the past. Of the 92 smokers with any history of spiritual resources, those smoking more than 15 cigarettes/day were significantly more receptive to provider encouragement of spiritual resources in a quit attempt (OR=5.4). Our data are consistent with overall beliefs in the United States about spirituality and recent trends to include spirituality in health care. We conclude that smokers, especially heavier smokers, may be receptive to using spiritual resources in a quit attempt and that spirituality in tobacco dependence treatment warrants additional investigation and program development.     

Recruitment of physician offices for an office-based adolescent smoking cessation study.

Physician office settings play an important role in tobacco cessation intervention. However, few tobacco cessation trials are conducted at these sites, in part because of the many challenges associated with recruiting community physician offices into research. The present study identified and implemented strategies for recruiting physician offices into a randomized clinical trial of tobacco screening and cessation interventions with adolescent patients. A total of 30 community physicians participated in focus groups to elicit their perceptions of facilitators of and barriers to initial engagement of physician practices and the subsequent enrollment of the practices in long-term research projects. Physicians identified facilitators such as (a) the involvement of office staff in the recruitment process and (b) on-site presentations of the study's background and aims. Some of the barriers identified were time commitment concerns and the lack of incentives in exchange for participation. These focus group findings were then integrated with theory-based and empirically driven recruitment strategies for a 12-month randomized tobacco intervention trial with adolescent patients. Of 185 office practices approached to participate (screened from a pool of 273 practices), 103 agreed to on-site presentations of the study. Subsequently, almost all of the practices (101) that received the presentation agreed to enroll in the study. Conclusions are that (a) recruitment is a multicomponent process, (b) the processes of communication, engagement, and enrollment must be carefully planned and implemented to achieve maximal results, and (c) the development of effective strategies for recruiting health care provider practices presents an important infrastructure for testing adolescent smoking cessation interventions.