Douglas E. Jorenby

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.

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.

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.

Safety and immunogenicity of a nicotine conjugate vaccine in current smokers

Immunotherapy is a novel potential treatment for nicotine addiction. The aim of this study was to assess the safety and immunogenicity of a nicotine conjugate vaccine, NicVAX, and its effects on smoking behavior. Smokers (N = 68) were recruited for a noncessation treatment study and assigned to 1 of 3 doses of the nicotine vaccine (50, 100, or 200 μg) or placebo. They were injected on days 0, 28, 56, and 182 and monitored for a period of 38 weeks. Results showed that the nicotine vaccine was safe and well tolerated. Vaccine immunogenicity was dose‐related (P<.001), with the highest dose eliciting antibody concentrations within the anticipated range of efficacy. There was no evidence of compensatory smoking or precipitation of nicotine withdrawal with the nicotine vaccine. The 30‐day abstinence rate was significantly different across the 4 doses (P = .02), with the highest rate of abstinence occurring with 200 μg. The nicotine vaccine appears to be a promising medication for tobacco dependence.

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.

Smoking withdrawal dynamics: II. Improved tests of withdrawal-relapse relations.

In this article, the authors assessed whether continuously scaled symptom parameters derived from growth models (T. M. Piasecki et al., 2003) are linked to smoking at long-term follow-up by using data from a large-scale clinical trial (N = 893). Results revealed that higher withdrawal intercepts, positive linear slopes, and greater volatility were all positively associated with relapse, and cigarette coefficients (indicating smoking-induced withdrawal reduction) were negatively related to relapse. In models keyed around the first lapse to smoking, those destined to lapse reported more severe withdrawal during abstinence, and withdrawal patterns discriminated groups defined according to lapse duration. The findings complement earlier heterogeneity studies in implicating the pattern of changing withdrawal symptoms over time as a factor strongly associated with smoking relapse.

Measures of Affect and Nicotine Dependence Predict Differential Response to Smoking Cessation Treatments.

Smokers (N = 126) were randomly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies (skills training or support) and 1 of 2 nicotine exposure strategies (nicotine gum or rapid smoking). Counseling and nicotine strategies were completely crossed; all four combinations resulted in equivalent 1-year abstinence rates. Skills training produced higher initial cessation and more coping responses posttreatment than did support. Rapid smoking, but not nicotine gum, produced tachycardia to the taste of cigarettes posttreatment, consistent with cigarette aversion. The treatments were differentially effective among subpopulations of smokers: Subjects high in pretreatment negative affect responded best to support counseling; those low in pretreatment negative affect responded best to skills training. Self-reports of pretreatment craving predicted response to the nicotine exposure treatments.

Immunogenicity and Smoking Cessation Outcomes for a Novel Nicotine Immunotherapeutic

NicVAX, a nicotine vaccine (3′AmNic‐rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double‐blinded, placebo‐controlled multicenter clinical trial (N = 301 smokers) tested the results of 200‐ and 400‐µg doses administered four or five times over a period of 6 months, as compared with placebo. 3′AmNic‐rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14–6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five‐injection, 400‐µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3′AmNic‐rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.