Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials.

Although bupropion and nicotine replacement therapy (NRT) are efficacious tobacco dependence treatments, there is substantial interindividual variability in therapeutic response and most smokers relapse. Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response. We investigated the roles of two functional genetic variants in the dopamine D2 receptor (DRD2) gene in response to pharmacotherapy for tobacco dependence among participants in two randomized clinical trials with a 6-month follow-up period: a double-blind placebo-controlled trial of bupropion (n=414) and an open label trial of transdermal nicotine vs nicotine nasal spray (n=368). At the end of the treatment phase, a statistically significant (p=0.01) interaction between the DRD2 - 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele. By contrast, smokers carrying the Del C allele had statistically significantly (p=0.006) higher quit rates on NRT compared to those homozygous for the Ins C allele, independent of NRT type. The C957T variant was also associated (p=0.03) with abstinence following NRT. These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 - 141 Ins C allele, while NRT may be more beneficial for those who carry the Del C allele. Study findings require confirmation in additional larger samples before they are applied in practice.

Effects of different nicotine replacement therapies on postcessation psychological responses.

Transdermal nicotine patch (TN) and nicotine nasal spray (NS) are both efficacious forms of smoking cessation treatment, but have different pharmacokinetic properties and modes of action. To understand better psychological responses to treatment, we investigated the effects of TN versus NS on positive affect, negative affect, and withdrawal symptoms during treatment. Participants were randomly assigned to receive TN (n=172) or NS (n=163) plus seven sessions of behavioral counseling, and completed self-report questionnaires at pretreatment and during treatment. TN participants, but not NS participants, reported significant increases in positive affect during treatment. Increases in negative affect and withdrawal were observed, independent of treatment. Only changes in negative affect predicted relapse by the end of the treatment phase. These findings indicate that, although TN may enhance positive affect for smokers in treatment compared with NS, only changes in negative affect predict treatment outcome.

Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial.

BACKGROUND: Despite the well-documented efficacy and different pharmacokinetic and pharmacodynamic properties of different forms of nicotine replacement therapy, empirical data are insufficient to guide practitioners in selecting a particular form of treatment for individual patients with tobacco dependence. OBJECTIVE: To evaluate the comparative efficacy of transdermal nicotine and nicotine nasal spray and identify predictors of treatment outcome. DESIGN: Randomized, open-label clinical trial with a 6-month follow-up period. SETTING: 2 university-based smoking cessation research programs. PARTICIPANTS: 299 treatment-seeking smokers who were followed for 6 months after the target quit date. INTERVENTION: Behavioral group counseling and 8 weeks of therapy with nicotine nasal spray or transdermal nicotine. MEASUREMENTS: Demographic characteristics, smoking history, depression symptoms, and body mass index were measured at baseline. Smoking practices were biochemically verified at the end of treatment and at 6 months after the target quit date. RESULTS: Abstinence rates for the transdermal nicotine and nicotine nasal spray groups were not significantly different at 6-month follow-up (15.0% vs. 12.2%, respectively; P > 0.2). Interactions in abstinence rates for subgroups of smokers were statistically significant (P < 0.05). Smokers who had low to moderate dependence levels, were not obese, and were white achieved higher abstinence rates with transdermal nicotine, whereas smokers who were highly dependent, obese, or members of minority groups achieved higher abstinence rates with nasal spray. LIMITATIONS: The subgroup findings need confirmation in additional large studies before they are routinely applied. CONCLUSIONS: Ethnicity, weight, and level of nicotine dependence may help identify smokers who have greater or lesser abstinence rates with either transdermal or nasal spray nicotine.

Individual differences in nicotine intake per cigarette.

The increase in levels of blood nicotine that occurs from smoking a single cigarette, sometimes referred to as a "nicotine boost," is an individualized measure of how much nicotine has been extracted from smoking a cigarette. This study investigated the demographic, smoking status, and psychological predictors of nicotine boost in a sample of 190 treatment-seeking smokers. Boost was assessed by comparing plasma nicotine levels before and after participants smoked one of their own brand cigarettes ad libitum. Positive affect (mood) was a significant positive predictor of nicotine boost, controlling for baseline cotinine levels and cigarette brand (Federal Trade Commission) nicotine delivery. However the proportion of variability accounted for in the model was relatively small (5%). Future research on individual differences in nicotine boost is warranted to clarify the role of psychological, physiological, and cigarette-related determinants.

Subjective effects of an initial dose of nicotine nasal spray predict treatment outcome.

RATIONALE: Nicotine nasal spray (NS) is recommended as one of five first-line smoking cessation products. A clinically convenient tool to identify smokers most likely to benefit from NS could assist healthcare practitioners in selecting the optimal treatment for individual patients. OBJECTIVES: To evaluate whether the subjective effects of an initial pre-treatment dose of NS predict 6 month abstinence rates following NS treatment for tobacco dependence. METHODS: One hundred and seventy-five smokers received an initial 1 mg pre-treatment dose of NS and completed a new measure of NS subjective effects (initial spray experience, ISE). This measure, together with demographic and smoking history variables, was examined as a predictor of 6-month point-prevalence (biochemically verified) abstinence rates. RESULTS: Factor analysis revealed positive and negative effects subscales of the ISE. Smokers with higher ratings of positive effects from the pre-treatment NS dose were significantly more likely to be abstinent at 6-month follow-up. These effects were partially mediated by reduction in urge to smoke. CONCLUSIONS: Pending additional validation in human laboratory and clinical studies, assessment of the acute positive subjective effects of initial NS delivery may be an efficient way to predict who will be successful with NS treatment for tobacco dependence.

Mediating mechanisms for the impact of bupropion in smoking cessation treatment.

Several studies have documented the effectiveness of bupropion for smoking cessation, yet little is known about the mechanisms by which it facilitates abstinence. In this placebo-controlled randomized trial. We examined whether bupropion's effects on cessation were mediated by changes in withdrawal and/or negative or positive affect (PA). Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo, plus behavioral counseling. Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models. Cotinine-verified 7-day point prevalence cessation rates at the end of treatment (8-weeks post quit date) were 48% for bupropion and 29% for placebo (P=0.001). There were significant treatment effects on withdrawal and negative affect (NA); however, only change in NA predicted cessation. In a path model, change in NA was a significant mediator of bupropion's effects on cessation. However, the proportion of variance accounted for by this mediator was small, suggesting that other unmeasured factors play an important role. Laboratory-based paradigms may be useful to identify other mediators of bupropion's effects, thereby pointing to mechanisms of effect that can be bolstered in future treatment studies.

Predictors of attendance in a randomized clinical trial of nicotine replacement therapy with behavioral counseling.

Participant attendance at smoking cessation-counseling sessions is an important factor in treatment outcome. In this study, we examined the influence of demographic, psychological, and smoking history variables on attendance at a randomized clinical trial comparing transdermal nicotine and nicotine nasal spray that included seven sessions of behavioral group counseling. Of the 353 participants, 70.5% attended all seven sessions. Perfect attendance predicted abstinence from cigarettes at the end of treatment and at 6-month follow-up. In a logistic regression model, higher levels of education and higher body mass index were significant independent predictors of better attendance. There was a significant interaction between type of nicotine replacement (transdermal nicotine vs. nasal spray) and sex: females were less likely than males to have perfect attendance in the nasal spray group, but there was no sex difference in attendance for the transdermal nicotine group. These findings suggest that smokers with lower body mass index and less formal education may benefit from proactive counseling to address individual barriers to attendance at smoking cessation counseling. Additional research in this area would also be valuable to evaluate strategies to promote attendance in these high-risk groups.

Cigarette smoking practices among American college students: review and future directions.

Cigarette smoking among college students is a critical public health problem. In this article, the authors review available research on cigarette smoking practices among college students and suggest directions for future research. Studies show that smoking by college students is associated with being White, living in housing where smoking is permitted, using alcohol and other substances, and having a lower psychological sense of well-being. Depression, life satisfaction, and coping style are also related to college smoking, but the causal relationship remains unclear. Although a large proportion of college students have made an attempt to quit smoking, only a minority actually succeed. Most study designs examining college smoking have been cross-sectional, descriptive, or both. Thus, conclusions regarding predictors of smoking onset, maintenance, and cessation cannot be made. Future studies should use longitudinal designs that can identify psychological and socioenvironmental determinants of smoking among college students. Such information could inform the development of smoking prevention and cessation interventions targeted to the college student population.

Alcohol consumption and partner violence among women entering substance use disorder treatment.

To test the hypothesized role of alcohol consumption as a proximal risk factor for partner violence, a within-subjects analysis compared levels of alcohol consumption in violent versus nonviolent conflict events among substance-abusing women and their male partners. Participants were married or cohabiting women (N = 145) who had recently begun a substance abuse treatment program and reported both a violent and a nonviolent relationship conflict event with their male partner in the prior 6 months. The average age was 38, and 83% were White. Male partners did not participate in the study. The female participant provided information about the male partner. Women were interviewed regarding a violent conflict event in which physical violence occurred and a nonviolent conflict event in which psychological aggression occurred without physical violence. The interview assessed quantity of alcohol consumed and use of other drugs prior to each conflict. Alcohol consumption was significantly greater prior to violent versus nonviolent conflict events for all measures of women's alcohol consumption examined: any drinking, heavy drinking, number of drinks in the 12 hr preceding the conflict event, and estimated blood alcohol concentration at time of the event. Male partners' alcohol consumption showed similar results. Use of other drugs in women, but not men, was significantly more likely prior to physical conflicts. These within-subject comparisons help to rule out individual difference explanations for the alcohol-violence association and indicate that the quantity of alcohol consumption is an important proximal risk factor for partner violence in substance-abusing women and their male partners. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Gender differences in smoking cessation in a placebo-controlled trial of bupropion with behavioral counseling.

Among smokers, women may be at greater risk than men for developing smoking-related diseases, perhaps because they have greater difficulty quitting smoking, as suggested by numerous studies. In the present study, we hypothesized that bupropion would reduce this gender disparity among 314 women and 241 men enrolled in a placebo-controlled, randomized trial using behavioral counseling plus 10 weeks of bupropion (300 mg). Prolonged abstinence and biochemically verified point prevalence outcomes were measured at end of treatment (8 weeks after the quit date) and at 6-month follow-up. A logistic regression model of 6-month prolonged abstinence and a Cox regression (survival analysis) model revealed a significant gender by smoking rate by drug interaction and a main effect for marital status. This three-way interaction suggests that bupropion particularly benefited men who smoked more than one pack of cigarettes per day at baseline and, conversely, women who smoked a pack or less. The point prevalence logistic regression model showed no evidence that either gender or smoking rate modified the effect of treatment. These results suggest that bupropion treatment may reduce the gender disparity in prolonged abstinence rates among lighter smokers.