Michael C. Fiore

A controlled trial of sustained - Release bupropion, a nicotine patch, or both for smoking cessation

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.

Addiction motivation reformulated: an affective processing model of negative reinforcement.

This article offers a reformulation of the negative reinforcement model of drug addiction and proposes that the escape and avoidance of negative affect is the prepotent motive for addictive drug use. The authors posit that negative affect is the motivational core of the withdrawal syndrome and argue that, through repeated cycles of drug use and withdrawal, addicted organisms learn to detect interoceptive cues of negative affect preconsciously. Thus, the motivational basis of much drug use is opaque and tends not to reflect cognitive control. When either stressors or abstinence causes negative affect to grow and enter consciousness, increasing negative affect biases information processing in ways that promote renewed drug administration. After explicating their model, the authors address previous critiques of negative reinforcement models in light of their reformulation and review predictions generated by their model.

A multiple Motives approach to tobacco dependence: The Wisconsin Inventory of Smoking Dependence Motives (WISDM-68)

The dependence construct fills an important explanatory role in motivational accounts of smoking and relapse. Frequently used measures of dependence are either atheoretical or grounded in a unidimensional model of physical dependence. This research creates a multidimensional measure of dependence that is based on theoretically grounded motives for drug use and is intended to reflect mechanisms underlying dependence. Data collected from a large sample of smokers (N = 775) indicated that all 13 subscales of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) have acceptable internal consistency, are differentially present across levels of smoking heaviness, and have a multidimensional structure. Validity analyses indicated the WISDM-68 subscales are significantly related to dependence criteria such as smoking heaviness and to 4th edition Diagnostic and Statistical Manual of Mental Disorders symptoms of dependence and relapse.

A Candidate Gene Approach Identifies the CHRNA5-A3-B4 Region as a Risk Factor for Age-Dependent Nicotine Addiction

People who begin daily smoking at an early age are at greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic variants and nicotine dependence assessed in adulthood will be stronger among smokers who began daily nicotine exposure during adolescence. We compared nicotine addiction—measured by the Fagerstrom Test of Nicotine Dependence—in three cohorts of long-term smokers recruited in Utah, Wisconsin, and by the NHLBI Lung Health Study, using a candidate-gene approach with the neuronal nAChR subunit genes. This SNP panel included common coding variants and haplotypes detected in eight α and three β nAChR subunit genes found in European American populations. In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity (p = 2.0×10−5; odds ratio = 1.82; 95% confidence interval 1.39–2.39) in subjects who began daily smoking at or before the age of 16, an exposure period that results in a more severe form of adult nicotine dependence. A substantial shift in susceptibility versus protective diplotype frequency (AA versus BC = 17%, AA versus CC = 27%) was observed in the group that began smoking by age 16. This genetic effect was not observed in subjects who began daily nicotine use after the age of 16. These results establish a strong mechanistic link among early nicotine exposure, common CHRNA5-A3-B4 haplotypes, and adult nicotine addiction in three independent populations of European origins. The identification of an age-dependent susceptibility haplotype reinforces the importance of preventing early exposure to tobacco through public health policies.

Predicting relapse back to smoking: Contrasting affective and physical models of dependence

Traditional models of physical dependence suggest that nicotine dependence should be reflected by the extent of drug exposure (e.g., smoking rate) and by evidence of physiological adaptation (e.g., withdrawal severity). An affective model suggests that nicotine dependence should be related to an individuals tendency to experience negative affect and expectations that nicotine use would ameliorate such affect. This research investigated the ability of these 2 models to predict relapse back to smoking at 6 months postquit. Logistic regression models were developed and tested in 505 heavy smokers participating in nicotine patch clinical trials. Results supported both models, but the most potent predictor of outcome was postquit negative affect, which accounted for much of the predictive validity of traditional measures of nicotine dependence. Affective reactivity appears to be a core constituent of dependence.

Prevalence and predictors of transitions in smoking behavior among college students.

The prevalence of smoking among college students is surprisingly high and represents a significant public health issue. However, there are few longitudinal studies of smoking in this population. This study examined the prevalence and predictors of transitions in smoking behavior among a cohort of 548 college students. Over the course of 4 years, 87% of daily smokers and almost 50% of occasional smokers continued to smoke. Among nonsmokers, 11.5% began smoking occasionally and none became daily smokers. In general, predictors of smoking behavior change were significant only among baseline occasional smokers and included gender, smoking outcome expectancies, and affect regulation expectations. Peer and parental smoking, demographics, affect, stress, and alcohol use were generally not predictive of change. Tobacco control interventions targeted at college students are clearly warranted.

Development and validation of the Wisconsin Smoking Withdrawal Scale.

The accurate assessment of nicotine withdrawal is important theoretically and clinically. A 28-item scale, the Wisconsin Smoking Withdrawal Scale, was developed that contains 7 reliable subscales tapping the major symptom elements of the nicotine withdrawal syndrome. Coefficients alpha for the subscales range from .75 to .93. This scale is sensitive to smoking withdrawal, is predictive of smoking cessation outcomes, and yields data that conform to a 7-factor structure. The 7 scales predicted intratreatment smoking, chi2(7, N = 163) = 15.19, p = .034. Moreover, the questionnaire is sufficiently brief so that it can be used in both clinical and research contexts.

A Randomized Placebo-Controlled Clinical Trial of 5 Smoking Cessation Pharmacotherapies

CONTEXT Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use. OBJECTIVE To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons. DESIGN A randomized, double-blind, placebo-controlled clinical trial. SETTING Two urban research sites. PATIENTS One thousand five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications. INTERVENTIONS Participants were randomized to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. In addition, all participants received 6 individual counseling sessions. MAIN OUTCOME MEASURES Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date (postquit), end of treatment (8 weeks postquit), and 6 months postquit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse. RESULTS All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (odds ratios, 1.63-2.34). With such protection, only the nicotine patch plus nicotine lozenge (odds ratio, 2.34, P < .001) produced significantly higher abstinence rates at 6-month postquit than did placebo. CONCLUSION While the nicotine lozenge, bupropion, and bupropion plus lozenge produced effects that were comparable with those reported in previous research, the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation.

Smoking Status as the New Vital Sign: Effect on Assessment and Intervention in Patients Who Smoke

OBJECTIVE To assess the effect of expanding the vital signs to include smoking status. DESIGN We prospectively conducted exit interviews with patients at a general internal medicine clinic in Madison, Wisconsin, during a 16-month period from 1991 to 1993. METHODS Patients were surveyed briefly before (N = 870) and after (N = 994) the implementation of a simple institutional change in clinical practice. This change involved training the staff in how to use progress notepaper with a vital sign stamp that included smoking status (current, former, or never) along with the traditional vital signs. Included in the survey were questions about whether the patient smoked, whether the patient was asked that day about smoking status (by a clinician or other staff), and, for smokers, whether they were urged to quit smoking and given specific advice on how to do so. RESULTS After expansion of the vital signs, patients were much more likely to report inquiries about their smoking status on the day of a clinic visit (an increase from approximately 58% at baseline to 81% at intervention; P < 0.0001). The vital sign intervention was associated with significant increases in the percentage of smokers who reported that their clinician advised them that day to quit smoking (from approximately 49% at baseline to 70% during the intervention; P < 0.01) and in the percentage who reported that their clinician gave them specific advice that day on how to stop smoking (from approximately 24% at baseline to 43% during the intervention; P < 0.01). CONCLUSION Expanding the vital signs to include smoking status was associated with a dramatic increase in the rate of identifying patients who smoke and of intervening to encourage and assist with smoking cessation. This simple, low-cost intervention may effectively prompt clinicians to inquire about use of tobacco and offer recommendations to smokers.

The Multiphase Optimization Strategy for Engineering Effective Tobacco Use Interventions

The multiphase optimization strategy (MOST) is a new methodological approach for building, optimizing, and evaluating multicomponent interventions. Conceptually rooted in engineering, MOST emphasizes efficiency and careful management of resources to move intervention science forward steadily and incrementally. MOST can be used to guide the evaluation of research evidence, develop an optimal intervention (the best set of intervention components), and enhance the translation of research findings, particularly type II translation. This article uses an ongoing study to illustrate the application of MOST in the evaluation of diverse intervention components derived from the phase-based framework reviewed in the companion article by Baker et al. (Ann Behav Med, in press, 2011). The article also discusses considerations, challenges, and potential benefits associated with using MOST and similar principled approaches to improving intervention efficacy, effectiveness, and cost-effectiveness. The applicability of this methodology may extend beyond smoking cessation to the development of behavioral interventions for other chronic health challenges.