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Biomedical subjects

Freda Patterson

Publications and source records attributed to Freda Patterson.

18 recordsLinked to original sources

Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation.

BACKGROUND: Nicotine is metabolized to cotinine, and cotinine is metabolized to 3'-hydroxycotinine (3-HC) by the liver enzyme cytochrome P450 (CYP) 2A6. More rapid metabolism of nicotine may result in lower nicotine blood levels from nicotine replacement products and poorer smoking cessation outcomes. This study evaluated the utility of the 3-HC/cotinine ratio as a predictor of the efficacy of nicotine replacement therapy as an aid for smoking cessation. METHODS: By use of an open-label design, 480 treatment-seeking smokers were randomly assigned to 8 weeks of transdermal nicotine or nicotine nasal spray use, plus behavioral group counseling. Assessments included demographics, smoking history, body mass index, and plasma nicotine, cotinine, and 3-HC concentrations, as well as CYP2A6 genotypes. Smoking cessation was biochemically verified at the end of treatment and at 6-month follow-up. RESULTS: The rate of nicotine metabolism, as indicated by pretreatment 3-HC/cotinine ratio derived from cigarette smoking, predicted the effectiveness of transdermal nicotine at both time points. The odds of abstinence were reduced by almost 30% with each increasing quartile of metabolite ratio (odds ratio, 0.72 [95% confidence interval, 0.57-0.90]; P=.005). Higher metabolite ratios also predicted lower nicotine concentrations (beta=-1.72, t(179)=-3.31, P<.001), as well as more severe cravings for cigarettes after 1 week of treatment (beta=0.32, t(190)=2.91, P=.004). The metabolite ratio did not predict cessation with use of nicotine nasal spray (odds ratio, 1.05 [95% confidence interval, 0.83-1.33]; P=.68). CONCLUSION: The nicotine metabolite ratio might be useful in screening smokers to determine likely success with a standard dose of transdermal nicotine.

Administration, Cutaneous↗

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.

Administration, Intranasal↗

Reduced nicotine reward in obesity: cross-comparison in human and mouse.

RATIONALE: Tobacco use and obesity lead to significant morbidity and mortality. OBJECTIVE: This study was conducted to investigate the factors maintaining smoking behavior in lean and obese individuals by utilizing a mouse/human cross-validation model of nicotine reward. METHODS: In humans, a cigarette choice paradigm was used to examine the relative reinforcing value of nicotine in obese and non-obese smokers. Conditioned place preference (CPP) for nicotine was assessed in mice fed standard low fat rodent chow and mice rendered obese by a high fat diet. RESULTS: In humans, obese smokers self-administered nicotine via cigarettes significantly less often than non-obese smokers and showed attenuated hedonic effects of nicotine-containing cigarettes compared to denicotinized cigarettes. Similarly, mice exposed to a high fat diet did not exhibit nicotine CPP, relative to control mice. mRNA levels for mu-opiate and leptin receptors were also downregulated in the ventral tegmental area of these mice. CONCLUSIONS: Together, these studies provide the first evidence for reduced nicotine reward in obese subjects and suggest that this may be mediated by dietary influences on the endogenous opioid system.

Animals↗

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.

RATIONALE: Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated. OBJECTIVE: This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes. METHODS: In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette. RESULTS: The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices. CONCLUSIONS: These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.

Adolescent↗

Treating tobacco dependence: state of the science and new directions.

Despite almost two decades of intensive tobacco control efforts, nearly one quarter of Americans continue to smoke. The two United States Food and Drug Administration-approved medications used to treat tobacco dependence, bupropion and nicotine replacement therapy, are effective for only a fraction of smokers. Investigations of medications approved for affective disorders and other forms of substance abuse, such as fluoxetine and naltrexone, have yielded mixed results as tobacco dependence treatments. A particular challenge in tobacco dependence treatment is the development of effective approaches for smokers with unique needs, such as cancer patients and pregnant women. Despite new developments in these areas, significant gaps in knowledge and practice remain. Basic research in the neurobiologic and genetic basis of nicotine dependence offers promise for the development of novel and more effective treatment approaches. For example, emerging research in pharmacogenetics explores how genetic variation in drug-metabolizing enzymes and drug targets modifies response to pharmacotherapy. These discoveries could someday help practitioners to individualize the type, dosage, and duration of tobacco dependence treatment based on genotype, and maximize the efficacy.

Female↗

Increases in hyperactive-impulsive symptoms predict relapse among smokers in nicotine replacement therapy.

Inattention and hyperactive-impulsive symptoms have been associated with nicotine dependence. In an open-label randomized trial (N = 454) of transdermal nicotine versus nicotine nasal spray, we examined whether increases in inattention and hyperactive-impulsive symptoms measured by self-report in the first quit week predicted relapse at the end of 8 weeks of treatment (EOT). During the first quit week, 166 (37%) participants reported an increase whereas 288 (63%) reported no change/decrease in total symptoms; changes were not influenced by treatment type. In a logistic regression model of abstinence, an increase in total symptoms in the first quit week significantly reduced odds of abstinence at EOT (continuous change score: OR = 0.94, 95% CI = 0.91-0.98, p = .002; dichotomized change score: OR = 0.57, 95% CI = 0.37-0.87, p = .009). Early increases in inattention and hyperactive-impulsive symptoms following quit date during nicotine replacement therapy predicted relapse to smoking, suggesting that treatments targeting these symptoms in the first quit week may facilitate abstinence.

Adult↗

Recurrent event analysis of lapse and recovery in a smoking cessation clinical trial using bupropion.

We report a reanalysis of data from a prior study describing the event history of quitting smoking aided by bupropion, using recurrent-event models to determine the effect of the drug on occurrence of lapses and recoveries from lapse (resumption of abstinence). Data were collected on 1,070 subjects across two similar double-blind randomized clinical trials of bupropion versus placebo and fitted with separate Cox regression models for lapse and recovery. Analyses were split using discrete time-varying covariates between the treatment (weeks 1-10) and follow-up phases (end of treatment to 12 months). Bupropion was associated with slower lapse during treatment for both sexes, and being female was associated with faster lapse across both phases. Drug did not affect time to recovery for males but was associated with faster recovery among females, allowing women to recover as quickly as men. High levels of nicotine dependence did not affect time to lapse but were associated with slower recovery from lapse across treatment and follow-up phases. During the treatment phase, higher levels of baseline depression symptoms had no effect on time to lapse but were associated with slower recovery from lapse. Results highlight the asymmetry in factors preventing lapse versus promoting recovery. Specifically, dependence, depression symptoms, and a sex x drug interaction were found to affect recovery but not lapse. Further research disentangling lapse and recovery events from summary abstinence measures is needed to help us develop interventions that take advantage of bupropion at its best and that compensate where it is weak.

Adult↗

Pharmacogenetics and nicotine addiction treatment.

This review focuses on the current status of, and future directions for, pharmacogenetic research on nicotine dependence and smoking cessation treatment. Pharmacological treatment involving nicotine replacement therapy and bupropion for nicotine addiction and smoking cessation has been shown to be efficacious when provided in combination with behavioral support. Cessation rates remain somewhat modest, however, and one possibility is that success rates may be enhanced by offering treatments tailored to an individual's genotype. Nonetheless, research on this issue remains in its infancy, and although the scope for individualized treatment tailored to genotype is promising, there are substantial practical, ethical and social considerations that must be addressed before such research is translated into clinical practice.

Bupropion↗

Changes in food reward following smoking cessation: a pharmacogenetic investigation.

RATIONALE: Despite the high prevalence and public health significance of weight gain following smoking cessation, little is known about the underlying bio-behavioral mechanisms or effective therapies. OBJECTIVES: We evaluated the effects of bupropion on food reward following smoking abstinence and the moderating influence of genotype. METHODS: Seventy-one smokers of European ancestry were genotyped for the dopamine D2 receptor ( DRD2) Taq1 polymorphism and randomized to treatment with bupropion (300 mg) or placebo for smoking cessation. Subjects participated in two behavioral laboratory sessions during which the rewarding value of food was assessed using a behavioral economics measure: session 1 occurred prior to medication and before cessation of smoking; session 2 occurred following 3 weeks of medication and 1 week of sustained abstinence. RESULTS: Carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and these effects were attenuated by bupropion treatment ( P=0.03 for medication by genotype interaction). Further, higher levels of food reward at session 2 (post-quit) predicted a significant increase in weight by 6-month follow-up in the placebo group, but not in the bupropion-treated group ( P=0.006 for medication by food reward interaction). CONCLUSIONS: These results provide new evidence that the increase in body weight that occurs following smoking cessation is related to increases in food reward, and that food reward is partly determined by genetic factors. Bupropion's efficacy in attenuating abstinence-induced weight gain may be attributable, in part, to decreasing food reward.

Adult↗

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.

Administration, Cutaneous↗

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.

Adult↗

Do small lapses predict relapse to smoking behavior under bupropion treatment?

Although bupropion is known to be an effective aid to smoking cessation, little is known about its mode of action. In the present study we tested the hypothesis that bupropion reduces the likelihood that a smoking lapse, or slip, leads to a subsequent relapse. This hypothesis was tested in the context of a clinical trial of bupropion as a smoking cessation aid, using Cox regression and representing lapse history as a discrete time-varying covariate. Bupropion treatment reduced the probability of relapse during the treatment phase (hazard ratio, or HR=.421, p< or =.000) but not during the follow-up phase (end of treatment to 6 months, HR=.896, p< or=.67). As anticipated, having small lapses during treatment contributed to or predicted subsequent relapse, both during treatment (HR=2.897, p< or =.000) and during follow-up (HR=2.320, p< or=.008). Although an interaction was found between drug treatment and lapse history in predicting subsequent failure during the treatment phase, the finding suggested that drug slightly increased the effect of lapse on eventual failure during treatment (HR=1.706, p<or=.012). No evidence was found that the effect of this interaction carried forward into follow-up (HR=1.500, p<or=.30). Although the mechanisms of action of bupropion may best be addressed in a human laboratory study, results from this clinical trial suggest that the effectiveness of bupropion treatment is not attributable to reducing the effect of a lapse in predicting relapse.

Adult↗

Smoking topography predicts abstinence following treatment with nicotine replacement therapy.

OBJECTIVE: Smoking topography refers to how a person smokes a cigarette and includes measures of the number of puffs and puff volume, duration, and velocity. This study examined the relationship between smoking topography and abstinence from cigarettes following nicotine replacement therapy. A secondary objective was to determine the relationship of smoking topography to carbon monoxide (CO) exposure. METHOD: Participants (n = 113) smoked one of their preferred brands of cigarette through a smoking topography device prior to participating in an open-label trial of transdermal nicotine versus nicotine nasal spray. A subset of participants (n = 50) provided breath CO samples prior to and following smoking the cigarette. RESULTS: Mean V(max) [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 1.02-1.24; P = 0.02], mean puff volume (OR, 0.95; 95% CI, 0.91-0.98; P = 0.01), mean interpuff interval (OR, 1.06; 95% CI, 1.00-1.11; P = 0.03), and cigarette type (full flavor versus light/ultralight; OR, 0.35; 95% CI, 0.14-0.89; P = 0.03) were significant predictors of abstinence in a model controlling for treatment group and nicotine dependence. Controlling for time since last cigarette and initial CO level, mean puff velocity (beta = 0.171; P = 0.01) was the only significant predictor of CO boost. CONCLUSION: These results suggest that smoking topography may be useful to predict abstinence after using nicotine replacement therapy and to assess harm from smoking.

Adult↗

Identifying and characterizing adolescent smoking trajectories.

Our understanding of longitudinal patterns of adolescent smoking development and the determinants of these patterns is limited. The present study evaluated adolescent smoking trajectories and characterized these trajectories with social, psychological, and behavioral factors in a cohort of adolescents assessed annually from grades 9 to 12. Complete data (smoking practices, novelty seeking, academic performance, substance use, peer smoking, physical activity and sports participation, and tobacco ad receptivity) were available on 968 participants; data were analyzed using latent class growth modeling. Four adolescent smoking trajectories emerged: never smokers, experimenters, earlier/faster smoking adopters, and later/slower smoking adopters. Early adopters were characterized by their high novelty seeking personality, depressive symptoms, poorer academic performance, and receptivity to tobacco advertising, as well as their exposure to other smokers, and use of other substances. Later adopters were characterized quite similarly to the early adopters, although they tended to perform better in school and to be more involved in sports. Experimenters also shared many of these same risk characteristics but to a lesser degree. Overall, never smokers were the most conventional in their profile. These data suggest that there is significant heterogeneity in the timing, rate, and intensity of smoking progression. Adolescent smoking prevention and intervention programs will need to consider this heterogeneity and tailor or enhance attention to risk and protective factors depending on the subpopulation.

Adolescent↗

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.

Administration, Cutaneous↗

Effecting behavior change: awareness of family history.

This article explores the use of family history of disease as a public health tool for risk stratification and improved disease prevention by drawing from previous research on women at moderate risk of developing breast cancer because of a positive family history. About one quarter to one third of women do not appear to be aware of the added risk a family history of breast cancer poses, and many women with a family history overestimate their risk. It is unclear whether risk perceptions are causally related to breast cancer screening in women with a family history. Exaggerated risk perceptions may not hinder breast cancer screening, unless accompanied by distress. Studies suggest that counseling women with a family history of breast cancer about their risk has a small and short-term effect on risk comprehension, a small effect on breast cancer screening, psychological benefits for some women, and unintended negative effects on screening for other women. Future research needs to consider the psychological, individual difference, and cultural variables that moderate counseling effects, recruitment biases, the prospective relationship between perceived risk and breast cancer screening, and whether risk perceptions and comprehension need to match objective risk to be an effective tool to promote screening.

Breast Neoplasms↗

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.

Adolescent↗

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.

Adolescent↗