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.     

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.     

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.     

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.     

Toward evidence-based Internet interventions: A Spanish/English Web site for international smoking cessation trials.

The Internet provides a medium to administer and evaluate evidence-based interventions for highly prevalent public health problems worldwide. The authors report a series of four Internet smoking cessation studies conducted in English and Spanish. These studies examined both outcome (self-reported 7-day abstinence) and mechanisms related to outcome (the impact of major depressive episodes [MDEs] on the likelihood of quitting). Over 4,000 smokers from 74 countries entered the studies. Studies 1 and 2 evaluated a standard smoking cessation guide (the "Guía"). Studies 3 and 4 were randomized trials comparing the Guía+ITEMs (individually timed educational messages) to the Guía+ITEMs+a mood management course. ITEMs were E-mails inviting participants back to the site at specific times. Online follow-up assessments resulted in completion rates of 44%-54% at 1 month and 26%-30% at 6 months in studies 1 and 2. Incentives and follow-up phone calls increased these rates to 70%, 66%, 65%, and 62% at 1, 3, 6, and 12 months in study 4. At 6 months, self-reported 7-day abstinence rates using missing = smoking data were 6% in studies 1 and 2, 10%-14% in study 3, and 20%-26% in study 4. The Guía+ITEMs condition tended to have higher quit rates, which reached significance at the 12-month follow-up in study 3 and at the 3-month follow-up in study 4. Smokers with past (but not current) MDEs tended to be the most likely to abstain and those with current MDEs the least likely. This trend reached significance in studies 1 and 4.     

Ecological momentary assessment of adolescent smoking cessation: a feasibility study.

Attempts to quit smoking by adolescents typically fail, even when aided by psychosocial and pharmacological treatments. Gaining a better understanding of the process of smoking cessation and relapse in this population could lead to improved treatments and increases in cessation rates. Ecological momentary assessment (EMA) has been used to describe the relapse process among adults, but not among adolescents. This study examined the feasibility of using EMA to examine relapse among adolescent smokers. Participants (N = 13) used a hand-held computer for 3 weeks to report on their smoking behavior, affect state, and exposure to smoking cues during a quit attempt (7 days prequit, 14 days postquit). All of the participants recorded a quit attempt and at least one lapse during the monitoring interval. Compliance with the protocol was generally high but decreased slightly over time. As with adults, evidence indicated that lapses were associated with craving, negative affect, and smoking cues. These data support the feasibility and potential value of using EMA with adolescent smokers.     

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.     

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.     

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.     

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.     

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.     

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.     

The effectiveness of a nurse-managed perinatal smoking cessation program implemented in a rural county.

The present study (a) examined the effectiveness of a nurse-managed smoking cessation program, that was totally integrated into routine perinatal care, on the cessation rates of pregnant smokers in a rural community, and (b) assessed the subject characteristics associated with smoking cessation success. Data were collected from a convenience sample of 194 pregnant women who stated that they were smokers at the onset of their pregnancies. The study compared the effects of usual care (n = 93) versus the Smoke Free Baby & Me program (n = 101), which included the American Cancer Society's Make Yours a Fresh Start Family program. Smoking status was measured by self-report and urinary cotinine at four points during pregnancy and postpartum. At the postpartum visit, more women in the experimental group reported that they were not smoking compared with those in the control group (37.3% vs. 16.7%), Pearson's chi2 (n = 87) = 4.37, p = .037, and they had higher validated (urinary cotinine <200 ng/ml) smoking cessation rates (n = 80, t = 2.449, p = .017) if they had quit smoking by the first prenatal visit. Smoking cessation was positively associated with level of education and negatively associated with gravidity, parity, the number of smokers in the household, and the number of cigarettes smoked per day at the first prenatal visit. Significant discordance was found between self-report and urinary cotinine assays at all prevalence points, regardless of group. In conclusion, this nurse-delivered program integrated into perinatal care influenced the smoking behaviors of "recent quitters" but had no effect on those who reported smoking at the first prenatal visit. Implications for clinical practice are discussed.     

Expressive writing as a smoking cessation treatment adjunct for young adult smokers.

This investigation evaluated the efficacy of expressive writing as a treatment adjunct to a brief office smoking cessation intervention plus nicotine patch therapy in young adults. Participants aged 18-24 years were randomized to a brief office intervention (n=99) or to an expressive writing plus brief office intervention (n=97). Both conditions received four individual visits plus 6 weeks of nicotine patch therapy, which began on the quit date following the week 2 visit. Participants in the expressive writing plus brief intervention condition wrote for 2 consecutive days before and 3 consecutive days after the quit date. The brief office intervention group completed a control writing assignment. At end of treatment (week 8), biochemically confirmed 7-day point-prevalence abstinence for the expressive writing plus brief office intervention condition was significantly greater than for the brief office condition (33% vs. 20%, p=.043, OR=2.0, 95% CI=1.0-3.7, from a logistic regression adjusting for gender). At 24 and 52 weeks, abstinence rates were similar for the brief office intervention versus expressive writing plus brief office intervention (12% vs. 11% at 24 weeks; 11% vs. 11% at 52 weeks). The results suggest that expressive writing has promise as a smoking cessation treatment adjunct for young adults. Lengthier interventions or the use of boosters should be tested to extend treatment effects. However, participants reported a low level of enthusiasm for the expressive writing, which may be a barrier to implementing it over a longer time frame. Therefore, other modes of delivering expressive writing to young adult cigarette smokers should be explored.     

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.     

Evaluation of a culturally appropriate smoking cessation intervention for Latinos

BACKGROUND: Many believe that smoking cessation programmes for Latinos should be tailored to the values and beliefs of the culture. However, randomised studies of culturally appropriate smoking cessation interventions with Latinos are rare. METHODS: Latino smokers (n = 313) were randomised to an intervention condition or a comparison group. The intervention was a three month programme based on social cognitive constructs and delivered in the smoker's home by trained lay health advisors, or promotores. Comparison group participants were referred to the California Smoker's Helpline in Spanish. Predictors of abstinence among all participants also were examined. RESULTS: About one week post-intervention, validated (carbon monoxide) past week abstinence rates were more than twice as high in the intervention group (20.5%) than in the comparison (8.7%) (p < or = 0.005). The pattern of results held for self reported abstinence, and after recoding dropouts to non-abstinence. The primary predictor of abstinence was number of cigarettes smoked per day at baseline, a common measure of addiction. CONCLUSIONS: The culturally appropriate intervention facilitated abstinence in Latino smokers, at least in the short term. Strengths and weaknesses of the study are discussed.     

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.