Craving, withdrawal, and smoking urges on days immediately prior to smoking relapse.

Rates of smoking relapse remain high, despite the wide availability of cessation aids. Presumably factors such as craving, withdrawal symptoms, and smoking urges are key contributors to relapse, but empirical support for this presumption is not conclusive and is complicated by the high variability in symptoms across individuals and time, as well as by the lack of an absolute symptom threshold for response. Data were analyzed from 137 female smokers, aged 18-40 years, who completed 30 days of a protocol for a longitudinal smoking cessation trial. Subjects were assigned a quit date and followed regardless of subsequent smoking status. At baseline, subjects completed written measures of nicotine craving, withdrawal symptoms, and smoking urges. They also completed these measures daily for 30 days, beginning on their quit date, Scores were standardized within subjects and graphed to identify temporal symptom patterns. A total of 26 women quit smoking and 111 relapsed (at least one cigarette puff). The intensity of subjects' craving, withdrawal, and smoking urges Factors 1 and 2 peaked on the day of relapse by an average of 1.4, 1.1, 1.2, and 1.1 standard deviations, respectively, with symptoms rising during the previous 2-5 days and dropping precipitously over the 2 days subsequent to relapse. Additionally, women who relapsed had higher absolute (unstandardized) symptom scores on their quit day than those who were abstinent for 30 days. These findings imply that escalation of withdrawal symptoms, craving, and smoking urges during a quit attempt may contribute to smoking relapse. Frequent symptom monitoring might be clinically important for relapse prevention.     

The role of impulsivity on smoking maintenance.

In order to better understand why those higher in impulsivity experience more difficulties during smoking abstinence, the current study examined the possible mechanisms contributing to cigarette smoking relapse. Fifty dependent cigarette smokers completed measures designed to assess craving, tobacco withdrawal severity, and negative affect during 48 hours of nicotine abstinence. Using a series of multilevel models (SAS Proc Mixed Procedure), significant impulsivity x time analyses revealed differences in craving, F(2, 96) = 3.74, p<.05, and anxiety, F(2, 96) = 3.23, p<.05. Simple slopes analyses indicated that heightened trait-impulsivity predicted greater increases in craving and anxiety during a 48-hour abstinence period. These findings suggest that smokers with higher levels of impulsivity may lack the ability to find an accessible and comparable substitute for cigarette smoking during a cessation attempt. This study also highlights the importance of considering individual differences when treating those who wish to quit smoking.     

Smokers' expectancies for nicotine replacement therapy vs. cigarettes.

Smokers (N=188) recruited from the local community completed a questionnaire that measured expected outcomes of using cigarettes, nicotine gum, nicotine patch, and nicotine nasal spray. Expectancy questions relating to negative affect, craving, weight, and health risks were derived from the Smoking Consequences Questionnaire-Adult. As predicted, smokers held much greater expectancies that cigarettes help control negative affect, craving, and weight relative to nicotine replacement therapy (NRT). All NRT products were expected to cause fewer health risks than cigarette smoking. As predicted, smokers held strong negative affect reduction expectancies for cigarette smoking. For NRT, although still relatively low, craving reduction was the strongest expectancy. Individuals who had experience using the nicotine patch had greater positive expectancies for NRT. Greater positive expectancies for NRT were correlated with more immediate plans to quit smoking. In summary, cigarette smokers' positive expectancies about cigarettes do not appear to generalize to NRT products, which may limit their use and effectiveness.     

Preliminary examination of tobacco withdrawal in adolescent smokers during smoking cessation treatment

Tobacco withdrawal symptoms have been shown to play a significant role in mediating relapse to smoking in adult smokers; however, few prospective studies have examined the course of tobacco withdrawal symptoms over time and their connection to lapse in adolescent smokers. Withdrawal symptoms were assessed weekly for 4 weeks in a sample of adolescent smokers participating in a pilot cessation intervention. Adolescent smokers experienced an exacerbation in overall withdrawal symptoms, particularly of cravings and restlessness, although symptoms were generally mild. The course of symptoms was different for boys and girls: Girls generally experienced a peak and subsequent decline in symptoms early in the establishment of abstinence, whereas boys experienced a constant level of symptoms that did not decline over the 4 weeks. Finally, withdrawal symptoms experienced on quit day were not related to lapse to smoking during the course of treatment for either boys or girls. These results suggest that although withdrawal symptoms may be uncomfortable, they may not be the most salient to a lapse to smoking for adolescent smokers attempting to quit. These findings have direct implications for the design and implementation of treatment of nicotine dependence in adolescent smokers.     

Depression predicts smoking early but not late in a quit attempt.

This study examined the relationship between depression history and smoking after a quit attempt. A total of 677 smokers participating in a randomized smoking cessation trial (Smith et al., 2001) provided data on current depression, depression history, and depression-related measures and smoking at 1 week and 6 months after a quit date. Depression history predicted smoking at 1 week postquit but not at 6 months postquit. Smoking during the first week was not predictive of smoking at 6 months in those with a history of depression but was predictive among those with no history of depression. Prediction models including depression history and depression-related measures (e.g., negative affect, negative cognitive style) showed that depression history was a powerful predictor of smoking early in the quit attempt.     

Transdermal nicotine use in postmenopausal women: does the treatment efficacy differ in women using and not using hormone replacement therapy?

This study of postmenopausal female smokers (N = 94) asked: During short-term smoking abstinence, do the beneficial effects of transdermal nicotine replacement therapy (NRT) on acute symptomatology (i.e., withdrawal, cigarette craving, smoking urges, mood, depressive symptoms, motor speed, and reaction time) differ in women who use and do not use hormone replacement therapy (HRT)? Participants were recruited according to HRT and non-HRT use (self-selecting), then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking.     

Treating smokers before the quit date: can nicotine patches and denicotinized cigarettes reduce cravings?

The present study investigated whether treatment with the combination of denicotinized cigarettes and 21-mg nicotine patch for 2 weeks before a designated quit date could lessen cravings for smoking, thereby helping smokers abstain from smoking. The study was a randomized controlled clinical trial conducted at Roswell Park Cancer Institute, Buffalo, New York, in 2004 and 2005. Patients included 98 adult heavy smokers (using 20 or more cigarettes/day). Half of the subjects received 2 weeks of combination of denicotinized cigarettes (Quest 3) and 21-mg nicotine patch for 2 weeks before the quit date. The remaining smokers were switched to light cigarettes (Quest 1) during the 2 weeks before the quit date. After the quit date, all subjects received counseling for smoking cessation and were provided nicotine patches for up to 8 weeks after the quit date. Self-reported cravings for smoking, withdrawal symptoms, and smoking abstinence were measured at predetermined intervals using phone-based surveys and in clinical visits. The group that used denicotinized cigarettes and nicotine patch before quitting reported less frequent and less intense cravings for cigarettes in the 2 weeks before and after the designated quit date. Self-reported withdrawal symptoms and quit rates did not differ significantly between the groups. The use of a denicotinized cigarette combined with the nicotine patch appears to lessen cravings to smoke in the immediate postcessation period. A larger, better-powered study is needed to test if this treatment combination has merit for increasing quit rates.     

Impulsivity and smoking relapse.

Previous research has shown that elevated trait-impulsivity heightens the risk for initiating tobacco use and indicates that nicotine may be disproportionately rewarding for more impulsive persons. However, the influence of impulsivity on the ability to maintain nicotine abstinence has not been studied. The present study tested the hypothesis that a higher level of trait-impulsivity would predict a more rapid relapse to smoking following 48 hr of nicotine abstinence. Participants were euthymic, regular smokers (N=45), with a history of at least one major depressive episode, who participated in a paid smoking cessation study with biological challenge (tryptophan depletion). Treatment involved a 1-day skills training workshop followed by 48 hr of bioverified abstinence and weekly follow-up for 1 month. Regression analyses indicated that elevated impulsivity predicted shorter time to relapse following the workshop after controlling for treatment condition, baseline nicotine dependence, and age (beta=-.39, R(2) change=.147, p=.011). Greater impulsivity predicted more rapid relapse to smoking, which mediational analyses indicated could not be explained by positive affect, negative affect, or craving. Findings suggest a need to identify alternative mechanisms to explain impulsive smokers' increased difficulty in maintaining abstinence and to develop targeted treatments that address the special needs of smokers high in impulsivity.     

Ecological momentary assessment of adolescent smoking cessation: a feasibility study.

Attempts to quit smoking by adolescents typically fail, even when aided by psychosocial and pharmacological treatments. Gaining a better understanding of the process of smoking cessation and relapse in this population could lead to improved treatments and increases in cessation rates. Ecological momentary assessment (EMA) has been used to describe the relapse process among adults, but not among adolescents. This study examined the feasibility of using EMA to examine relapse among adolescent smokers. Participants (N = 13) used a hand-held computer for 3 weeks to report on their smoking behavior, affect state, and exposure to smoking cues during a quit attempt (7 days prequit, 14 days postquit). All of the participants recorded a quit attempt and at least one lapse during the monitoring interval. Compliance with the protocol was generally high but decreased slightly over time. As with adults, evidence indicated that lapses were associated with craving, negative affect, and smoking cues. These data support the feasibility and potential value of using EMA with adolescent smokers.     

School-based smoking cessation programs for adolescents: what predicts attendance?

The present study examined contextual and individual predictors of attendance in a 10-session school-based teen smoking cessation program. Participants were 349 students at 29 Illinois high schools. Predictor variables included demographics, smoking history, psychosocial variables, and social environment variables. School-level characteristics of interest included proportion of low-income students, group size, and program timing. Overall attendance was predicted by higher motivation and less stress at baseline. Students also were more likely to attend if they had already tried to quit, were more dependent on nicotine, and had more positive smoking expectancies. Percentage of low-income students and program timing also predicted program attendance; students were more likely to attend the program at schools with lower percentages of low-income students and where the program was offered during the school day. We also examined predictors of attendance before and after quit week (week 5). Early in the program, only the school-level variables (program timing and percentage of low-income students) predicted attendance. After quit week, the school variables also were important, and baseline motivation and perceived stress also predicted attendance at these sessions. Results highlight the importance of individual characteristics in determining program participation, as well as the importance of considering school context and programmatic issues when planning school-based smoking cessation programs.     

Preliminary evidence of the association between the history of childhood attention-deficit/hyperactivity disorder and smoking treatment failure.

Smoking rates are elevated among individuals with attention-deficit/hyperactivity disorder (ADHD). The association of ADHD diagnosis and smoking treatment outcome has not been examined. The present study examined abstinence rates among 428 adult smokers participating in two randomized controlled trials. Treatments included nicotine replacement, antidepressants, and psychological interventions. Childhood ADHD was assessed retrospectively by diagnostic interview. In a survival analysis, ADHD status predicted time to relapse after controlling for gender, history of depression, and baseline smoking variables. Only 1 of 47 participants with a history of childhood ADHD remained abstinent by week 52, compared with 18% of those who had no history of childhood ADHD (adjusted OR=0.36, 95% CI=0.28-0.45). The current findings provide preliminary evidence for an association between childhood ADHD and smoking cessation treatment failure. Further investigation is warranted.     

Motives for smoking and their correlates in clients attending Stop Smoking treatment services.

This study investigated smokers' ratings of putative smoking motives and how these relate to smoking patterns, withdrawal symptoms, and short-term abstinence in clients attending smokers' clinics. Data were collected from 2,727 clients from two London Stop Smoking Services that offered behavioral support combined with pharmacotherapy. On a scale of 1 to 5, stress relief (M = 3.9), boredom relief (3.7), and enjoyment (3.6) were rated highest. Uses as an aid to concentration (2.9), for relief of withdrawal discomfort (2.8), and as an aid to socialization (2.8) received moderate ratings. Weight control was rated low (2.0). These ratings were found to be largely independent of each other. Ratings of enjoyment, boredom relief, improvement in concentration, and relief of withdrawal discomfort were positively correlated with daily cigarette consumption (p<.001). Ratings of smoking for withdrawal relief, enjoyment, improvement in concentration, stress relief, and boredom relief were positively correlated with nicotine dependence as measured by the Fagerstr?m Test for Nicotine Dependence (p<.001). Strength of urges to smoke and time spent with urges to smoke in the first week of abstinence were positively correlated with smoking for withdrawal relief, to stay alert, to improve concentration, and with enjoyment of smoking (p<.01). Relapse to smoking within 4 weeks was not associated with ratings of any of the smoking motives, including enjoyment. Although correlated with a measure of dependence, no strong connection appears to exist between relapse and any of the smoking motives, suggesting that the mechanisms underlying nicotine dependence lie at a deeper level, outside the ability of smokers to be introspective regarding their motivations.     

The nicotine dependence syndrome scale: a multidimensional measure of nicotine dependence.

We report the development of a new multidimensional questionnaire to measure nicotine dependence, based on Edwards's syndromal conceptualization of dependence. We present three studies. In study 1, we administered the Nicotine Dependence Syndrome Scale (NDSS) to 317 smokers in a smoking cessation study. Factor analysis of the NDSS revealed five factors: Drive (craving and withdrawal, and subjective compulsion to smoke), priority (preference for smoking over other reinforcers), tolerance (reduced sensitivity to the effects of smoking), continuity (regularity of smoking rate), and stereotypy (invariance of smoking). A single overall score based on the first principal component, NDSS-T, was retained as a single core measure of dependence. The NDSS showed promising psychometric properties: NDSS-T and factor scores showed strong associations with dependence-relevant measures, even when we controlled for scores on the Fagerstr?m Tolerance Questionnaire (FTQ); and the NDSS predicted urges when smoking, withdrawal in acute abstinence, and outcome in cessation. The five factor scores showed differential patterns of correlations with external validators, supporting the multidimensionality of the measure. In study 2, we revised the NDSS to expand some subscales and administered it to 802 smokers in a cessation study. The same five factors were extracted, the internal reliability of some subscales was improved, and the factor scores again showed associations with dependence-relevant validators, which were largely maintained when we controlled for FTQ scores. In study 3, with 91 smokers in a cessation trial, we established that the test-retest reliability of the subscales was adequate. Thus, the NDSS presents a valid multidimensional assessment of nicotine dependence that may expand on current measures.     

Smoking cessation by socioeconomic status and marital status: the contribution of smoking behavior and family background.

We studied socioeconomic status and marital status as predictors of smoking cessation, adjusting for previous smoking behavior and family background by using a large Finnish prospective twin dataset unselected for smoking behavior. The data were collected by postal surveys in 1981 and 1990, and the sample comprised 3,069 current smokers, of whom 20% had quit smoking by 1990. Logistic regression analyses of all twin individuals and conditional logistic regression analysis of discordant pairs were used to predict smoking cessation. High education predicted smoking cessation among both men (OR=2.32, 95% CI=1.31-4.10) and women (OR=3.98, 95% CI=1.85-8.51) as did high social class among women. Additionally, starting at a late age, smoking a small number of cigarettes per day, and a low level of nicotine per cigarette predicted cessation. Socioeconomic differences in cessation diminished only slightly when we adjusted for smoking behavior factors. Among the twin pairs who were discordant in terms of smoking cessation, the twin who continued smoking also smoked more on average at baseline (men: OR=.94, 95% CI=.89-.99; women: OR=.82, 95% CI=.71-.94). The male twins who continued smoking had a smaller probability of getting married during the follow-up than had the cotwin who had quit smoking (OR=3.91, 95% CI=1.02-15.02). Indicators of socioeconomic status were important predictors of smoking cessation even when we adjusted for previous smoking behavior. For men, marriage was associated with an increased probability of cessation     

A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation

A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/-0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.     

Recommendation for the assessment of tobacco craving and withdrawal in smoking cessation trials.

This paper addresses methodological issues in the assessment of nicotine withdrawal and craving in clinical trials of smoking cessation therapies. We define withdrawal as a syndrome of behavioral, affective, cognitive, and physiological symptoms, typically transient, emerging upon cessation or reduction of tobacco use and causing distress or impairment of behavioral function. Offset effects (effects related to removal of a direct nicotine effect) are sustained effects of cessation or reduction of tobacco use that cause distress or impairment. Withdrawal and craving are important as potential predictors of relapse, as mediators and markers of treatment effects, and as clinical phenomena in their own right. Symptoms recommended for assessment include craving, irritability, depression, restlessness, sleep disturbance, difficulty concentrating, increased appetite, and weight gain; anxiety deserves further study. We recommend reporting of data on each of these individual symptoms, and use of multiple-item assessments. Although some standardized measures of withdrawal have promising psychometric properties, no measure has yet fully established its reliability, validity, and broad applicability and, therefore, we do not currently favor universal adoption of any one measure. Assessment of objective indices of withdrawal (e.g., hormonal changes) is currently technically challenging and of unknown value. Although weekly assessment may suffice in some large trials, more intensive measurement can provide better sensitivity. Analyses of withdrawal should include baseline measures and be sensitive to potential instability in baseline. Analytic approaches should take into account potential bias when only abstinent subjects are examined. Conversely, heterogeneity should be considered when smoking subjects are included in intent-to-treat analyses. Withdrawal data from clinical trials focused on assessing abstinence rates may be biased because of progressive subject loss to dropout and relapse; different designs and approaches are needed to investigate the process and natural history of craving and withdrawal.     

A twin study of smoking, nicotine dependence, and major depression in men.

This study examined the nature of the relationship among lifetime major depression, smoking, and nicotine dependence. Subjects were 8,169 male twins from the Vietnam Era Twin Registry. Biometrical modeling demonstrated a genetic influence on daily smoking, nicotine dependence, and major depression, and a family environmental influence on daily smoking. Genetic factors influencing nicotine dependence also strongly influenced major depression. We also compared probands with a history of major depression (n = 398) from pairs discordant for major depression, their nondepressed cotwins (n = 364), and controls (n = 1,863) on a number of secondary smoking outcomes. Major depression was associated with current daily smoking and certain nicotine withdrawal symptoms. Individuals with a familial vulnerability for major depression, even without a personal history of major depression, were more likely to smoke despite a serious illness and to report nervousness, restlessness, difficulty concentrating, and depressed mood during past quit attempts. Among the 237 monozygotic pairs discordant for major depression, depressed probands were more likely to have a lifetime history of nicotine dependence than were cotwins. Findings extend Kendler and colleague's (1993) study of female twins by demonstrating in men that shared genetic factors predispose not only to major depression and daily smoking but also to major depression and nicotine dependence.     

Smoking during the night: prevalence and smoker characteristics.

We report on the smoking patterns and characteristics of individuals who smoke at night. We also explore the relationship between night smoking, nicotine dependence, and cessation outcomes. Participants (N = 691) were heavy smokers enrolled in cessation research clinics. Data were from three studies. Using ecological momentary assessment, participants monitored their smoking (ad libitum, day and night) on electronic diaries (EDs) during a 2-week baseline period and for 4 weeks following a target quit day. A total of 41% of smokers recorded at least one episode of night smoking. Within this group, night smoking occurred on 26% of nights, averaging two episodes per night. ED data correlated with a single self-report item assessing the frequency of night smoking. Night smoking was associated with greater nicotine dependence and daily caffeine consumption. It also predicted risk for lapsing beyond traditional measures of nicotine dependence. Night smoking is common, is associated with nicotine dependence, and it represents additional risk for cessation failure. People who smoke at night may need nicotine replacement therapy overnight. Future research should determine whether treatments that improve sleep quality also improve cessation outcomes in night smokers.     

"Withdrawal symptoms" in adolescents: a comparison of former smokers and never-smokers.

Since the early 1980s, investigators have been reporting that adolescent smokers felt "dependent" on cigarettes and that adolescents trying to quit smoking experienced the same withdrawal symptoms observed in adult quitters, including restlessness, insomnia, increased appetite and weight gain, irritability or anger, depression, craving for cigarettes, and trouble concentrating. We hypothesized that most of these symptoms might be attributed to adolescence itself. To investigate this hypothesis, we examined the prevalence of these seven "adult" withdrawal symptoms in a population of adolescent former smokers and never-smokers. Participants were high school students in Houston, Texas, participating in a nested, group-randomized control group study designed to estimate the impact of a CD-ROM intervention for smoking prevention and cessation. We measured differences in symptoms frequency between never-smokers and former smokers, matched in a 2:1 ratio on sex and race/ethnicity, and differences in symptoms among former smokers as a function of time since final quit attempt and prior level of smoking. Only former heavy smokers have shown significantly higher prevalence of withdrawal symptoms compared with never-smokers. Of the seven symptoms assessed, only craving incrementally increased with the intensity of smoking. Overall the individual withdrawal symptoms did not effectively differentiate between 112 never-smokers and 34 former lighter smokers (persons who used to smoke less than "a few cigarettes on most days"). Withdrawal symptoms can reliably differentiate former heavy smokers from light smokers and never-smokers, among adolescents. Because most adolescents tend to be lighter smokers, future tobacco use and cessation studies should interpret adult withdrawal symptoms among adolescents with caution.