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

Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison, WI 53711, USA.
Archives of general psychiatry (Impact Factor: 14.48). 11/2009; 66(11):1253-62. DOI: 10.1001/archgenpsychiatry.2009.142
Source: PubMed


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.
To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons.
A randomized, double-blind, placebo-controlled clinical trial.
Two urban research sites.
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.
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.
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.
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.
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.

    • "In the course of treatment for smoking cessation, a practitioner may switch medications when patients are struggling and vulnerable to a lapse (Ebbert et al. 2009a, b, 2014; Issa et al. 2013; Karam-Hage et al. 2010; Koegelenberg et al. 2014; Piper et al. 2009; Rigotti 2012; Rose and Behm 2014; Steinberg et al. 2009). Although a common practice, little is known about the impact of switching pharmacotherapies. "
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    ABSTRACT: Rationale: Pharmacotherapies are often utilized to aid in smoking cessation, and switching medication when treating nicotine dependence has become more commonplace. Although common, little is known about the impact of the initial therapy on the effects of the subsequent therapy. Objectives: To begin to fill this gap in our understanding, this project determined how switching compounds that share stimulus elements with nicotine during extinction altered extinction responding and generalization of this extinction back to nicotine. Methods: Rats were trained in a discriminated goal-tracking task where nicotine administration was followed by intermittent sucrose access; sucrose was withheld following saline administration. In experiment 1, nornicotine supplanted nicotine in extinction sessions 1-3 and then a switch to varenicline on extinction sessions 4-6 was examined. In experiment 2, the reverse was investigated; varenicline to start extinction and then a switch to nornicotine. Generalization of extinction back to the nicotine stimulus was then assessed by generating a cumulative dose-effect curve. Results: Generalization of extinction back to the training nicotine stimulus was greater if nornicotine had been received at any point in extinction compared to only receiving varenicline. Whereas, extinction with varenicline alone showed more generalization to lower doses of nicotine. Conclusions: A switch in cessation pharmacotherapy during extinction did not impede or enhance generalization back to the nicotine-training stimulus. The nornicotine stimulus appears to share more stimulus overlap with the 0.4 mg/kg nicotine stimulus and varenicline may share more overlap with lower nicotine doses.
    No preview · Article · Sep 2015 · Psychopharmacology
    • "Participants were eligible if they were 18 years of age or older, and smoked 10 or more cigarettes per day (Piper et al., 2009). The University of Wisconsin-Madison IRB approved this trial, and all subjects provided written informed consent. "
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    ABSTRACT: Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings. Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Jun 2015 · Drug and alcohol dependence
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    • "Combination NRT provided the greatest nicotine withdrawal relief among all the conditions and was the only treatment that reduced withdrawal symptoms to baseline levels. A recent secondary analysis of the large scale RCT of 5 smoking cessation pharmacotherapies (Piper et al., 2009), demonstrated that greater suppression of smoking craving was the mechanism by which combination therapy resulted in significantly higher quit rates than monotherapy (Bolt, Piper, Theobald, & Baker, 2012). It has also been suggested, though not proven, that the addition of acute NRT to nicotine patch treatment may afford smokers a tool for reacting to acute episodes of craving that may arise even on patch treatment, and which are associated with smoking lapses (Ferguson & Shiffman, 2009). "
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    ABSTRACT: Cigarette smoking creates a substantial public health burden. Identifying new, effective smoking cessation interventions, optimizing existing interventions and promoting effective use of approved medications is a priority. When used as directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is opportunity for improving its effectiveness. Until recently, NRT use guidelines advised smokers to begin using NRT on their quit date, only to use 1 NRT formulation at a time, to refrain from using NRT while smoking, and to stop NRT within 3 months regardless of progress. The Food and Drug Administration (FDA) issued a recent announcement allowing for NRT labeling changes with applications from pharmaceutical companies for such changes, and we applaud this decision. Nevertheless, additional revisions are warranted by current research. There is robust evidence that combining a longer-acting form (e.g., patch) with a shorter-acting form (e.g., lozenge) is more effective than NRT monotherapy and is safe. Moreover, extant evidence suggests that NRT use prior to a quit attempt or for smoking reduction as part of a quit attempt is safe, and as effective as starting NRT on quit date, and specifically prequit nicotine patch increases quit rates and may engage additional recalcitrant smokers. Last, NRT use longer than 3 months is safe and may be beneficial for relapse prevention in some smokers. This report summarizes the FDA announcement, reviews the evidence for further revisions to current FDA NRT guidelines, and makes recommendations for over-the-counter (OTC) NRT labeling to allow for: combined use of faster-acting NRT medications with nicotine patch; nicotine patch use prior to quit date or NRT for smoking reduction as part of a quit attempt; and prolonged NRT for up to 6 months without healthcare provider consultation.
    Full-text · Article · Jun 2014 · Nicotine & Tobacco Research
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