Does reducing withdrawal severity mediate nicotine patch efficacy? A randomized clinical trial.

Nicotine replacement therapy (NRT) repeatedly has been shown to improve smoking treatment outcome. The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal. The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal, collected by ecological momentary assessments administered on a palm-top computer. Smokers (N = 324) were randomized to receive either active high-dose (35 mg) 24-hr patches or placebo. Increases in positive affect and decreases in craving, negative affect, and attention disturbance severity were related to lower risk of lapsing. Although NRT treatment did significantly decrease withdrawal and craving severity, these reductions only partially accounted for NRT's impact on time to first lapse: The results from a mediation analysis showed that the hazard ratio for NRT, when controlling for withdrawal and craving severity, was only a third to a half lower than the uncontrolled hazard ratio for NRT alone. This suggests that other mechanisms for the effectiveness of NRT need to be examined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analyzing milestones in smoking cessation: Illustration in a nicotine patch trial in adult smokers.

Tests of addiction treatments seldom reveal where treatment exercises its effect (i.e., promoting initial abstinence, preventing lapses, and/or impeding progression from lapse to relapse). The authors illustrate analyses distinguishing effects on these milestones in a randomized trial of high-dose nicotine patch (35 mg; n = 188) versus placebo (n = 136) in adult smokers, who used electronic diaries to monitor smoking in real time during 5 weeks of treatment. High-dose patch promoted initial abstinence (hazard ratio [HR] = 1.3) and decreased the risk of lapsing among those who achieved abstinence (HR = 1.6). The biggest effect of treatment was to prevent progression to relapse among those who had lapsed (HR = 7.1). Analysis of effects by milestones may enhance understanding of cessation treatments and their mechanisms of action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking.

Little research has examined the association of tobacco dependence with nicotine tolerance or reinforcement in a clinical sample. Smokers preparing to quit smoking participated in laboratory sessions to assess nicotine tolerance on subjective, cardiovascular, and performance measures and to assess nicotine reinforcement using a choice procedure. Participants were then provided with individual counseling (but no medication), made a quit attempt, and were followed for 1 year to determine clinical outcome, as determined by postquit withdrawal and days to relapse. Nicotine tolerance was unrelated to either withdrawal or relapse. However, acute nicotine reinforcement was significantly related to both greater withdrawal and faster relapse. Results challenge the common assumption that nicotine tolerance is closely related to dependence but suggest that nicotine reinforcement may have theoretical and clinical significance for dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multimodal approach to assessing the impact of nicotine dependence, nicotine abstinence, and craving on negative affect in smokers.

We used multimodal measurement to evaluate whether (a) nicotine dependence is associated with baseline and postquit negative affect and craving, (b) smoking relapse is associated with greater negative affect and craving than abstinence, and (c) craving is associated with negative affect. Treatment-seeking smokers were randomly assigned to either a brief behaviorally based smoking-cessation treatment condition or to a delayed treatment control condition. Participants in the treatment condition attended four assessment sessions, 4–5 days prequit (baseline), 1–2 days postquit, 3–5 days postquit, and 10–14 days postquit, while controls attended four sessions spaced over the same intervals. Retrospective questionnaires were collected at the beginning of each session, and corrugator EMG and in-session ratings were collected during viewing of affective and cigarette-related slides. The multimodal measures indicated that more dependent smokers experienced greater negative affect and craving at baseline and postquit, regardless of abstinence status. The self-report measures indicated that both relapsed and abstinent smokers reported greater negative affect and craving than control smokers. Craving was associated with negative affect across measurement modalities. These results highlight the benefits of using multimodal measures to study the impact of nicotine dependence and withdrawal on negative affect and craving. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Experimental evidence for a causal relationship between smoking lapse and relapse.

In this study, the authors prospectively evaluated the impact of a smoking lapse on relapse probability. After 4 days of smoking abstinence, 60 smokers were randomly assigned to smoke 5 nicotine-containing or 5 denicotinized cigarettes, or to remain abstinent (no lapse) during a 4-hr time period. Afterward, smoking abstinence was encouraged with monetary incentives, and smoking behavior was tracked for 6 days. Relative to the no-lapse condition, exposure to either of the cigarette types more than doubled the probability of subsequent smoking. Smoking outcomes did not differ between nicotine-containing and denicotinized cigarettes. The data suggest that stimulus factors may play an important role in lapse to relapse processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smoking Withdrawal Dynamics: III. Correlates of Withdrawal Heterogeneity.

Five parameters of postcessation smoking withdrawal variability derived from clinical data (T. M. Piasecki, D. E. Jorenby, S. S. Smith, M. C. Fiore, & T. B. Baker, 2003a, 2003b) were predicted from baseline measures and pharmacotherapy assignment. Smokers who were more dependent, older, and high in negative affect reported more severe withdrawal. Women, heavier smokers, and those with a history of depression reported more variable symptoms. Smokers treated with nicotine patch, bupropion, or both reported less severe withdrawal than did those given placebo, but medication did not affect the slope of symptoms over time, day-to-day variability of symptoms, or the size of acute changes in symptoms associated with lapses to smoking. Prior research has shown that these symptom facets predict later relapse: thus, current pharmacotherapies may aid cessation by diminishing withdrawal severity, but they do not affect all clinically important aspects of withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 × 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch.

Genetic and personality trait moderators of tobacco abstinence–symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with 1 or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Combined effects of venlafaxine, nicotine replacement, and brief counseling on smoking cessation.

In this study, 147 smokers were randomly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling (9 weekly sessions) and transdermal nicotine replacement therapy (22 mg/day). Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting, with the daily dose titrated from 150 to 225 mg. in response to symptoms of negative affect and relapse. The results showed no main effect of treatment on abstinence. Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen. Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation. The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers, in addition to the expected benefits of nicotine replacement therapy and behavioral counseling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurement of the effects of abstinence from tobacco: A qualitative review.

This article reviews terms, methodologies, and scales used to describe the effects of abstinence from tobacco in humans. The review suggests operational definitions for withdrawal, offset, novel, and indefinite abstinence effects. The review recommends the use of prospective studies that use smokers trying to quit, multiple data points preabstinence and very soon after abstinence, comparison groups, at least 16 hrs of abstinence, objective measures, measures of clinical significance, and data analytic techniques that allow use of all participants' data. The 8 most commonly used tobacco withdrawal measures differ in coverage, brevity, and use of single vs. multiple items to describe each symptom. Of the measures, 6 consistently increase with abstinence, but no single measure appears superior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of transdermal nicotine on tobacco/nicotine abstinence and the effects of a concurrently administered cigarette in women and men.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in ≥8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Over-the-counter nicotine replacement therapy: Can its impact on smoking cessation be enhanced?

Nicotine replacement therapies (NRTs) are efficacious smoking-cessation aids. However, only minimal increases in smoking cessation followed NRTs being made available over-the-counter (OTC), which presumably made these treatments more readily available. To better understand why the United States did not experience improvements in smoking cessation following the OTC availability of NRTs, it is useful to review factors that determine NRT's impact on smoking cessation and how these factors played out with the introduction of OTC NRT. The authors contend that for NRTs to have a greater impact on public health, increases are needed in the number of individuals making a quit attempt, the proportion using NRTs in a quit attempt, and the effectiveness of each quit attempt. Even small increases in the impact of OTC NRTs could yield significant benefits in terms of morbidity and mortality. The remainder of this article provides examples of interventions designed to target each of the aforementioned factors individually as well as examples of interventions that link increased cessation attempts, increased NRT reach, and increased NRT efficacy in order to synergistically enhance the impact of OTC NRTs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia.

This study was conducted to examine the effects of contingent monetary reinforcement (CM) for smoking reduction, with and without transdermal nicotine, on cigarette smoking in individuals with schizophrenia. Fourteen outpatients participated in each of 3 conditions: (a) CM combined with 21 mg transdermal nicotine, (b) CM combined with placebo patch, and (c) noncontingent reinforcement combined with placebo patch. Each condition lasted 5 days. Carbon monoxide levels were measured 3 times daily, and nicotine withdrawal symptoms were measured once daily in each condition. Results indicated that CM reduced smoking but that 21 mg transdermal nicotine did not enhance that effect. These results offer further evidence supporting the efficacy of CM for reducing smoking among people with schizophrenia, but higher doses of nicotine replacement therapy, or another pharmacotherapy, may be needed to enhance that effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating nicotine replacement therapy and stage-based therapies in a population-based effectiveness trial.

Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England Veterans Affairs Medical Center. Telephone interviews were completed with 3,239 smokers, and 2,054 agreed to participate (64%). Participants were randomly assigned to one of four conditions: stage-matched manuals (MAN); NRT plus manuals (NRT = MAN); expert system plus NRT and manuals (EXP = NRT = MAN); and automated counseling plus NRT, manuals, and expert system (TEL = EXP = NRT = MAN). Assessments were completed at baseline, 10, 20, and 30 months. The point prevalence cessation rates at final follow-up (30 months) were MAN, 20.3%; NRT = MAN, 19.3%; EXP = NRT = MAN, 17.6%; and TEL = EXP = NRT = MAN, 19.9%. Stage-matched manuals provided cessation rates comparable with previous studies. The addition of NRT, expert system interventions, and automated telephone counseling failed to produce a further increase in intervention effectiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Silver acetate interactions with nicotine and non-nicotine smoke components.

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The acute effects of nicotine on positive and negative affect in adolescent smokers.

Although adolescent cigarette smoking remains a critical public health concern, little is known about the reinforcing mechanisms governing smoking in this vulnerable population. To assess predictions derived from both positive and negative reinforcement models of drug use, the authors measured the acute effects of nicotine, as administered via tobacco cigarettes, on both positive and negative affect in a group of 15- to 18-year-old smokers. A matched group of nonsmokers served as a comparison group. Findings revealed that whereas adolescents who smoked a cigarette experienced reductions in both positive and negative affect, the observed reductions in negative affect were moderated by nicotine content of the cigarette (high yield vs. denicotinized), level of nicotine dependence, level of baseline craving, and smoking expectancies pertinent to negative affect regulation. Nonsmokers experienced no change in affect over the 10-min assessment period, and no interaction effects were observed for positive affect. Overall, the findings conform to a negative reinforcement model of nicotine effects and strongly suggest that, even among young light smokers, nicotine dependence and resultant withdrawal symptomatology may serve as motivating factors governing smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterizing nicotine withdrawal in pregnant cigarette smokers.

Maternal smoking is a leading preventable cause of poor pregnancy outcomes and infant morbidity and mortality. Whereas pregnancy has been thought of as a "window of opportunity" when women are more motivated to change health behaviors such as smoking, only 20% of pregnant women quit smoking upon learning they are pregnant and remain abstinent at the end of the pregnancy. Greater understanding of possible obstacles to smoking during pregnancy, such as nicotine withdrawal, is needed. The symptoms of nicotine withdrawal have been well characterized in nonpregnant smokers, but there has been only 1 report conducted during pregnancy, and that was a retrospective study. The aim of the present study was to characterize nicotine withdrawal and craving in pregnant cigarette smokers. These data were collected as part of prospective clinical trials assessing the efficacy of voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum. The authors examined results from the Minnesota Nicotine Withdrawal Scale (J. R. Hughes & D. K. Hatsukami, 1998) in 27 abstainers (reported no or very low levels of smoking, which was confirmed biochemically) and 21 smokers (smoked at >80% of their baseline smoking level) during the first 5 days of a cessation attempt. Abstainers reported more impatience, anger, and difficulty concentrating than did smokers. The results also suggest that pregnant smokers generally may have elevated baseline levels of withdrawal, which need to be considered in the design and analysis of future studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Practicing self-control lowers the risk of smoking lapse.

Recent research has suggested that practicing small acts of self-control can lead to an improvement in self-control performance. Because smoking cessation requires self-control, it was hypothesized that a treatment that builds self-control should help in quitting smoking. A total of 122 smokers either practiced small acts of self-control for 2 weeks before quitting smoking or practiced a task that increased their awareness of self-control or feelings of confidence, without exercising self-control. Their smoking status was assessed using daily telephone calls and biochemically verified. Individuals who practiced self-control remained abstinent longer than those who practiced tasks that did not require self-control. Supplemental analyses suggested that the increased survival times were a product of building self-control strength and were not produced by changes in feelings that practicing should help in cessation, effort exerted on the practice task, or thinking more about self-control while practicing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)