Tanya R. Schlam

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.

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.

Anxiety Diagnoses in Smokers Seeking Cessation Treatment: Relations with Tobacco Dependence, Withdrawal, Outcome, and Response to Treatment

AIMS To understand the relations among anxiety disorders and tobacco dependence, withdrawal symptoms, response to smoking cessation pharmacotherapy and ability to quit smoking. DESIGN Randomized placebo-controlled clinical trial. Participants received six 10-minute individual counseling sessions and either: placebo, bupropion SR, nicotine patch, nicotine lozenge, bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge. SETTING Two urban research sites. PARTICIPANTS Data were collected from 1504 daily smokers (>9 cigarettes per day) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use. MEASUREMENTS Participants completed baseline assessments, the Composite International Diagnostic Interview and ecological momentary assessments for 2 weeks. FINDINGS A structured clinical interview identified participants who ever met criteria for a panic attack (n = 455), social anxiety (n = 199) or generalized anxiety disorder (n = 99), and those who qualified for no anxiety diagnosis (n = 891). Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms. Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect. Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies. CONCLUSIONS Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke, elevated withdrawal, lack of response to pharmacotherapy and impaired ability to quit smoking. These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses.

Gender, race, and education differences in abstinence rates among participants in two randomized smoking cessation trials

INTRODUCTION Smoking is the leading preventable cause of morbidity and mortality in the United States, but this burden is not distributed equally among smokers. Women, Blacks, and people with low socioeconomic status are especially vulnerable to the health risks of smoking and are less likely to quit. METHODS This research examined cessation rates and treatment response among 2,850 participants (57.2% women, 11.7% Blacks, and 9.0% with less than a high school education) from two large cessation trials evaluating: nicotine patch, nicotine lozenge, bupropion, bupropion + lozenge, and nicotine patch + lozenge. RESULTS Results revealed that women, Blacks, and smokers with less education were less likely to quit smoking successfully than men, Whites, and smokers with more education, respectively. Women did not appear to benefit more from bupropion than from nicotine replacement therapy, but women and smokers with less education benefited more from combination pharmacotherapy than from monotherapy. DISCUSSION Women, Blacks, and smokers with less education are at elevated risk for cessation failure, and research is needed to understand this risk and develop pharmacological and psychosocial interventions to improve their long-term cessation rates.

Psychiatric disorders in smokers seeking treatment for tobacco dependence: relations with tobacco dependence and cessation.

OBJECTIVE The present research examined the relation of psychiatric disorders to tobacco dependence and cessation outcomes. METHOD Data were collected from 1,504 smokers (58.2% women; 83.9% White; mean age = 44.67 years, SD = 11.08) making an aided smoking cessation attempt as part of a clinical trial. Psychiatric diagnoses were determined with the Composite International Diagnostic Interview structured clinical interview. Tobacco dependence was assessed with the Fagerström Test of Nicotine Dependence (FTND) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). RESULTS Diagnostic groups included those who were never diagnosed, those who had ever been diagnosed (at any time, including in the past year), and those with past-year diagnoses (with or without prior diagnosis). Some diagnostic groups had lower follow-up abstinence rates than did the never diagnosed group (ps < .05). At 8 weeks after quitting, strong associations were found between cessation outcome and both past-year mood disorder and ever diagnosed anxiety disorder. At 6 months after quitting, those ever diagnosed with an anxiety disorder (OR = .72, p = .02) and those ever diagnosed with more than one psychiatric diagnosis (OR = .74, p = .03) had lower abstinence rates. The diagnostic categories did not differ in smoking heaviness or the FTND, but they did differ in dependence motives assessed with the WISDM. CONCLUSION Information on recent or lifetime psychiatric disorders may help clinicians gauge relapse risk and may suggest dependence motives that are particularly relevant to affected patients. These findings also illustrate the importance of using multidimensional tobacco dependence assessments.

New methods for tobacco dependence treatment research

IntroductionDespite advances in tobacco dependence treatment in the past two decades, progress has been inconsistent and slow. This paper reviews pervasive methodological issues that may contribute to the lack of timely progress in tobacco treatment science including the lack of a dynamic model or framework of the cessation process, inefficient study designs, and the use of distal outcome measures that poorly index treatment effects. The authors then present a phase-based cessation framework that partitions the cessation process into four discrete phases based on current theories of cessation and empirical data. These phases include: (1) Motivation, (2) Precessation, (3) Cessation, and (4) Maintenance.DiscussionWithin this framework, it is possible to identify phase-specific challenges that a smoker would encounter while quitting smoking, intervention components that would address these phase-specific challenges, mechanisms via which such interventions would exert their effects, and optimal outcome measures linked to these phase-specific interventions. Investigation of phase-based interventions can be accelerated by using efficient study designs that would permit more timely development of an optimal smoking cessation treatment package.

Interventions for Tobacco Smoking

Around 19% of US adults smoke cigarettes, and smoking remains the leading avoidable cause of death in this country. Without treatment only ~5% of smokers who try to quit achieve long-term abstinence, but evidence-based cessation treatment increases this figure to 10% to 30%. The process of smoking cessation comprises different pragmatically defined phases, and these can help guide smoking treatment development and evaluation. This review evaluates the effectiveness of smoking interventions for smokers who are unwilling to make a quit attempt (motivation phase), who are willing to make a quit attempt (cessation phase), who have recently quit (maintenance phase), and who have recently relapsed (relapse recovery phase). Multiple effective treatments exist for some phases (cessation), but not others (relapse recovery). A chronic care approach to treating smoking requires effective interventions for every phase, especially interventions that exert complementary effects both within and across phases and that can be disseminated broadly and cost-effectively.

Anhedonia as a Component of the Tobacco Withdrawal Syndrome

Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this topic has not been addressed definitively in research with humans. This research sought to determine whether anhedonia is (a) an element of the tobacco withdrawal syndrome in humans and (b) an impediment to successful tobacco cessation. Data were from 1,175 smokers (58.3% women; 85.5% White) participating in a randomized double-blind, placebo-controlled trial of smoking cessation pharmacotherapies. Ecological momentary assessments for 5 days before and 10 days after the target quit day were used to assess anhedonia and other established withdrawal symptoms. Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change in response to tobacco cessation and was associated with the severity of other withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated with decreased latency to relapse (hazard ratio = 1.09, 95% confidence interval [CI] [1.02, 1.17]) and with lower 8-week point-prevalence abstinence (odds ratio = .91, 95% CI [.86, .97])-relations that remained significant when other withdrawal symptoms were included as predictors. Finally, nicotine replacement therapy nearly fully suppressed the increase in abstinence-related anhedonia (β = -.66, p < .001), suggesting agonist suppression of withdrawal. Results suggest that anhedonia is a unique and motivationally significant element of the tobacco withdrawal syndrome in humans. These results have implications for defining and assessing tobacco use disorder and for understanding and treating tobacco addiction.

Identifying effective intervention components for smoking cessation: a factorial screening experiment

AIMS To identify promising intervention components intended to help smokers to attain and maintain abstinence in their quit smoking attempts. DESIGN A fully crossed, six-factor randomized fractional factorial experiment. SETTING Eleven primary care clinics in southern Wisconsin, USA. PARTICIPANTS A total of 637 adult smokers (55% women, 88% white) motivated to quit smoking who visited primary care clinics. INTERVENTIONS Six intervention components designed to prepare smokers to quit, and achieve and maintain abstinence (i.e. for the preparation, cessation and maintenance phases of smoking treatment): (1) preparation nicotine patch versus none; (2) preparation nicotine gum versus none; (3) preparation counseling versus none; (4) intensive cessation in-person counseling versus minimal; (5) intensive cessation telephone counseling versus minimal; and (6) 16 versus 8 weeks of combination nicotine replacement therapy (nicotine patch  +  nicotine gum). MEASUREMENTS Seven-day self-reported point-prevalence abstinence at 16 weeks. FINDINGS Preparation counseling significantly improved week 16 abstinence rates (P = .04), while both forms of preparation nicotine replacement therapy interacted synergistically with intensive cessation in-person counseling (P < 0.05). Conversely, intensive cessation phone counseling and intensive cessation in-person counseling interacted antagonistically (P < 0.05)-these components produced higher abstinence rates by themselves than in combination. CONCLUSIONS Preparation counseling and the combination of intensive cessation in-person counseling with preparation nicotine gum or patch are promising intervention components for smoking and should be evaluated as an integrated treatment package.

Comparative effectiveness of intervention components for producing long-term abstinence from smoking: a factorial screening experiment

AIMS To identify promising intervention components that help smokers attain and maintain abstinence during a quit attempt. DESIGN A 2 × 2 × 2 × 2 × 2 randomized factorial experiment. SETTING Eleven primary care clinics in Wisconsin, USA. PARTICIPANTS A total of 544 smokers (59% women, 86% white) recruited during primary care visits and motivated to quit. INTERVENTIONS Five intervention components designed to help smokers attain and maintain abstinence: (1) extended medication (26 versus 8 weeks of nicotine patch + nicotine gum); (2) maintenance (phone) counseling versus none; (3) medication adherence counseling versus none; (4) automated (medication) adherence calls versus none; and (5) electronic medication monitoring with feedback and counseling versus electronic medication monitoring alone. MEASUREMENTS The primary outcome was 7-day self-reported point-prevalence abstinence 1 year after the target quit day. FINDINGS Only extended medication produced a main effect. Twenty-six versus 8 weeks of medication improved point-prevalence abstinence rates (43 versus 34% at 6 months; 34 versus 27% at 1 year; P = 0.01 for both). There were four interaction effects at 1 year, showing that an intervention components effectiveness depended upon the components with which it was combined. CONCLUSIONS Twenty-six weeks of nicotine patch + nicotine gum (versus 8 weeks) and maintenance counseling provided by phone are promising intervention components for the cessation and maintenance phases of smoking treatment.