Addiction

Early stimulus funding supports research in adolescent addiction

Administrator — Tue, 09 Jun 2009 05:00:00 +0000

(Brown University) Robert Miranda Jr., assistant professor (research) with the Brown University Center for Alcohol and Addiction Studies, will examine whether the drug topiramate can help reduce marijuana addiction among teens. The National Institutes of Health and the Amerian Recovery and Reinvestment Act of 2009 awarded him more than $560,000 for the first year of what will be a two-year study. Miranda's research grant is one of the first in the country to use stimulus funding.

Effects of smoking abstinence, smoking cues and nicotine replacement in smokers with ...

Administrator — Wed, 27 May 2009 03:35:57 +0000

By Tidey J.W., Rohsenow D.J., Kaplan G.B., Swift R.M., Adolfo A.

The mechanisms underlying the low smoking cessation rates among smokers with schizophrenia (SS) are unknown. In this laboratory study, we compared the responses of 21 SS and 21 non-psychiatric controls (CS) to manipulations of 5-hour smoking abstinence, transdermal nicotine replacement (0mg, 21mg and 42mg), and in vivo smoking cues. Results indicate that SS were more sensitive than CS to the effects of acute abstinence on carbon monoxide (CO) boost, but not more sensitive to the effects of abstinence on urge levels or withdrawal symptoms. SS and CS did not differ in urge response to in vivo smoking cues, but SS were less consistent in their reactions. These findings suggest that heightened sensitivity to the effects of abstinence on smoke intake may partially account for the low cessation rates experienced by SS, but other potential mechanisms should...

Correspondence of interactive voice response (IVR) reports of nicotine withdrawal, craving, and ...

Administrator — Wed, 27 May 2009 03:34:08 +0000

By Toll B.A., Cooney J.L., McKee S.A., O'Malley S.S., Cooney N.L.

This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of nicotine withdrawal, craving, and depressive symptoms. However, the sample size decreased on each day of IVR reporting due...

Assessing dimensions of nicotine dependence:

Administrator — Wed, 27 May 2009 03:33:01 +0000

An evaluation of the Nicotine Dependence Syndrome Scale (NDSS) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM)

By Piper M.E., McCarthy D.E., Bolt D.M., Smith S.S., Lerman C., Benowitz N., Fiore M., Baker T.

Considerable research, ranging from survey to clinical to genetic, has utilized traditional measures of tobacco dependence, such as the Fagerstrom Test of Nicotine Dependence (FTND) and the Diagnostic and Statistical Manual (4th ed.) (DSM-IV) criteria, that focus on endpoint definitions of tobacco dependence such as heavy smoking, time to first cigarette in the morning, and smoking despite consequences. In an effort to better understand possible theories and mechanisms underlying tobacco dependence, which could be used to improve treatment and research, two multidimensional measures of tobacco dependence have been developed: the Nicotine Dependence Syndrome Scale (NDSS) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). This research...

A Placebo-Controlled Trial of Bupropion Combined with Nicotine Patch for Smoking Cessation in ...

Administrator — Wed, 27 May 2009 03:31:55 +0000

By George T.P., Vessicchio J.C., Sacco K.A., Weinberger A.H., Dudas M.M., Allen T.M., Creeden C.L., Potenza M.N., Feingold A., Jatlow P.I.

Background: Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (~22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia. Methods: A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26). Results: Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n...

Varenicline as compared to bupropion in smoking-cessation therapy

Administrator — Wed, 27 May 2009 03:12:49 +0000

Cost-utility results for Sweden 2003

By Bolin K., Mork A.-C., Willers S., Lindgren B.

Study objectives: To calculate incremental cost-utility ratios (cost per QALY gained) for varenicline (Champix; Pfizer), as compared to bupropion, in smoking-cessation programmes for a lifetime follow-up period. Design: The Benefits of Smoking Cessation on Outcomes (BENESCO) simulation model was used for a male and female cohort, respectively, as a point of departure but further extended in order to include the indirect effects of smoking-cessation on production and consumption in the economy. All calculations were performed in 2003 Swedish prices.

Setting: Sweden in 2003. Patients or participants: Model cohort consisting of 25% of all smokers among men and women (168,844 males and 208,737 females), distributed by age, 18 and older, as in the Swedish population of 2003.

Interventions: Varenicline as...

Adjusted indirect comparison may be less biased than direct comparison for evaluating new ...

Administrator — Wed, 27 May 2009 03:12:16 +0000

By Song F., Harvey I., Lilford R.

Objective: To investigate discrepancies between direct comparison and adjusted indirect comparison in meta-analyses of new versus conventional pharmaceutical interventions.

Study Design and Setting: Results of direct comparison were compared with results of adjusted indirect comparison in three meta-analyses of new versus conventional drugs. The three case studies are (1) bupropion versus nicotine replacement therapy for smoking cessation, (2) risperidone versus haloperidol for schizophrenia, and (3) fluoxetine versus imipramine for depressive disorders.

Results: In all the three cases, effects of new drugs estimated by head-to-head trials tend to be greater than that by adjusted indirect comparisons. The observed discrepancies could not be satisfactorily explained by the play of chance or by bias and heterogeneity in adjusted indirect comparison. This observation, along with analysis of possible systematic bias in the direct comparisons, suggested that the...

Human abuse liability of the smoking cessation drug varenicline in smokers and nonsmokers

Administrator — Wed, 27 May 2009 03:11:26 +0000

By McColl S.L., Burstein A.H., Reeves K.R., Billing Jr. C.B., Stolar M., Sellers E.M.

Varenicline is an (alpha)(4)(beta)(2) nicotinic acetylcholine receptor partial agonist developed as an aid for smoking cessation.This study evaluated varenicline's potential for abuse by smokers (n = 23) and nonsmokers (n = 22). The study useda randomized, double-blind, placebo-controlled, double-dummy crossover design with five treatment periods: 15 and 30 mg amphetamine, 1 and 3 mg varenicline, and placebo. Following each treatment, the participants were assessedon aspects relating to potential abuse of the drug (e.g., drug liking, drug high, and drug monetary value).The positive effects measured for 3 mg varenicline were similar to those for the placebo, and significantly lower than those for amphetamine in both smokers and nonsmokers. Unpleasant effects were reported for 3 mg vareniclinein both participant groups. For 1 mg varenicline, the overall patterns were similar, with the exception that thenonsmokers group...

Genetic variation in the dopamine D4 receptor gene and smoking cessation

Administrator — Wed, 27 May 2009 03:05:02 +0000

Follow-up of a randomised clinical trial of transdermal nicotine patch

By David S.P., Munafo M.R., Murphy M.F.G., Proctor M., Walton R.T., Johnstone E.C.

Smokers of European ancestry (n = 720) who participated in a double-blind, randomised, placebo-controlled trial of transdermal nicotine replacement therapy, were genotyped for two functional polymorphisms (variable number of tandem repeats (VNTR) and a C to T transition at position -521 (C-521T)) in the dopamine D4 receptor gene (DRD4) gene. Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism. For the DRD4 VNTR models, the main effect of treatment was significant at both 12-week (P = 0.001) and 26-week (P = 0.006) follow-ups, indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo.

The main effect of DRD4 VNTR...

Efficacy and Safety of Varenicline for Smoking Cessation

Administrator — Wed, 27 May 2009 03:04:29 +0000

By Hays J.T., Ebbert J.O., Sood A.

Effective treatment of nicotine addiction is essential for reducing the substantial current and predicted morbidity and mortality associated with tobacco smoking. Despite the availability of effective treatments for smoking cessation, such as nicotine replacement therapy and bupropion sustained-release (SR), abstinence rates remain less than optimal. Varenicline is the first in a new class of agents for smoking cessation, the (alpha)(4)(beta)(2) nicotinic acetylcholine receptor (nAChR) partial agonists. Nicotine addiction is mediated by stimulation of central (alpha)(4)(beta)(2) nAChRs by nicotine, which causes the release of dopamine, ultimately leading to the pleasurable effects of smoking. As a nAChR partial agonist, varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine and also reduces the rewarding effects of nicotine obtained from smoking in patients who lapse. Thus, varenicline offers a new therapeutic option for the treatment of nicotine addiction. Clinical trials...

Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms

Administrator — Wed, 27 May 2009 03:02:42 +0000

Rewarding effects of smoking during a quit attempt

By West R., Baker C.L., Cappelleri J.C., Bushmakin A.G.

Aims: To examine the effect of varenicline, a selective alpha4-beta2 nicotinic acetylcholine receptor (nAChR) partial agonist, on craving and withdrawal symptoms in smokers making a quit attempt and the rewarding effects of smoking during a lapse after the target quit date (TQD).

Materials and methods: Pooled data were analysed from two identical double-blind, randomised trials comparing varenicline 1 mg BID, bupropion (sustained release) 150 mg BID and placebo using measures of craving and withdrawal in the first week after the TQD (in abstinent [n=612] and non-abstinent participants [n=1,155]) and of the rewarding effects of the first cigarette smoked in non-abstinent participants.

Results: In abstinent and non-abstinent participants combined, varenicline reduced craving more than bupropion (p<0.01) and...

Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a ...

Administrator — Wed, 27 May 2009 03:00:02 +0000

An in vitro-in vivo study

By Feng B., Obach R.S., Burstein A.H., Clark D.J., De Morais S.M., Faessel H.M.

Varenicline is predominantly eliminated unchanged in urine, and active tubular secretion partially contributes to its renal elimination. Transporter inhibition assays using human embryonic kidney 293 cells transfected with human renal transporters demonstrated that high concentrations of varenicline inhibited substrate uptake by hOCT2 (IC(50)=890 (mu)M), with very weak or no measurable interactions with the other transporters hOAT1, hOAT3, hOCTN1, and hOCTN2. Varenicline was characterized as a moderate-affinity substrate for hOCT2 (K(m)=370 (mu)M) and its hOCT2-mediated uptake was partially inhibited by cimetidine. Co-administration of cimetidine (1,200 mg/day) reduced the renal clearance of varenicline in 12 smokers, resulting in a 29.0% (90% CI: 21.5%-36.9%) increase in systemic exposure. This increase is not considered clinically relevant, as it should not give rise to safety concerns....

A randomized controlled clinical trial of bupropion SR and individual smoking cessation counseling

Administrator — Wed, 27 May 2009 02:53:26 +0000

By McCarthy D.E., Piasecki T.M., Lawrence D.L., JorenD.E., Shiffman S., Fiore M.C., Baker T.B.

Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a randomized, placebo-controlled clinical trial among adult daily smokers. Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated, relative to a placebo medication and assessment control condition. Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment, relative to the placebo medication conditions, for both biochemically confirmed 7-day point-prevalence abstinence (OR=1.97, 95% CI 1.04-3.72) and self-reported prolonged abstinence (OR=2.90, 95% CI 1.66-5.06). Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses. Medication effects were more modest for both 12-month point-prevalence abstinence (OR=1.47, 95% CI 0.74-2.92) and prolonged...

Menstrual phase effects on smoking cessation: A pilot feasibility study

Administrator — Wed, 27 May 2009 02:52:17 +0000

By Carpenter M.J., Saladin M.E., Leinbach A.S., Larowe S.D., Upadhyaya H.P.

Background and Objectives: A growing body of research suggests that nicotine withdrawal and cigarette craving may vary across the menstrual cycle and that the luteal phase of the cycle may be associated with increases in each. This potential relationship suggests that careful timing of quit attempts during the menstrual cycle may improve initial success at abstinence, although there are no direct tests of this approach yet published. Our objectives were to preliminarily test the effect of timing of quit attempts for smoking cessation relative to menstrual cycle and to identify methodological procedures that could guide subsequent, larger clinical trials. Methods: In this pilot study, we randomized female smokers aged 18-40 who were not currently using hormonal contraception to quit smoking during either the follicular (n = 25) or luteal phase (n = 19) of their menstrual...

Smoking cessation pharmacotherapy preferences in rural primary care

Administrator — Wed, 27 May 2009 02:51:40 +0000

By Cupertino A.P., Richter K.P., Cox L.S., Nazir N., Greiner A., Ahluwalia J.S., Ellerbeck E.F.

Pharmacotherapy is a critical adjunct to smoking cessation therapy. Little is known about relative preferences for these agents among smokers in primary care settings. In the context of a population-based clinical trial, we identified 750 smokers in primary care practices and independent of their readiness to quit offered them a free treatment course of either bupropion or transdermal nicotine replacement (TNR). Smokers opting for pharmacotherapy completed standardized contraindication screens that were reviewed by the patient's primary care physician. Most participants (67%) requested pharmacotherapy. Use of pharmacotherapy was positively associated with higher nicotine dependence and readiness to quit. Of the smokers requesting pharmacotherapy, 51% requested bupropion and 49% requested TNR. Choice of bupropion was related to no history of heart disease and no previous use of bupropion. Although potential contraindications to treatments were...

Effect of transdermal nicotine replacement on alcohol responses and alcohol ...

Administrator — Wed, 27 May 2009 02:50:20 +0000

By McKee S.A., O'Malley S.S., Shi J., Mase T., Krishnan-Sarin S.

Rationale: Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior.

Objective: The primary aim of this within-subject, double-blind study was to examine whether transdermal nicotine replacement (0 mg vs 21 mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior.

Materials and methods: Subjects (n=19) were non-treatment-seeking, non-dependent heavy drinkers who were daily smokers. Six hours after transdermal patch application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03 g/dl] were assessed. This was followed by a 2-h self-administration period where subjects could choose to consume up to eight additional drinks (each...

Effect of genetic polymorphisms on smoking cessation

Administrator — Wed, 27 May 2009 02:46:30 +0000

A trial of bupropion in Korean male smokers

By Han D.-H., Joe K.-H., Na C., Lee Y.-S.

BACKGROUND: Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome.

OBJECTIVES: The aim of this study is to elucidate the question of whether the abstinence rates by bupropion trial would be different depending on the genotypes.

METHODS: Six candidate genes, thought to be involved in the interaction of nicotine and bupropion (for example, the dopamine receptor type 2, dopamine transporter, norepinephrine transporter, serotonin transporter, catecholamine-O-methyltransferase), and the clinical outcomes of smoking behavior were investigated. The participants were 225 male smokers to whom 150 mg of bupropion SR was administered for 4 weeks. The...

A pilot community-based intensive smoking cessation intervention in African American

Administrator — Wed, 27 May 2009 02:45:59 +0000

Feasibility, acceptability and early outcome indicators

By King A., Sanchez-Johnsen L., Van Orman S., Cao D., Matthews A.

Few intensive and community-based smoking cessation treatment programs have been designed for African-American smokers, a group who experiences numerous health disparities associated with cigarette smoking.

The purpose of this study was to examine the feasibility, acceptability and biochemically verified early outcome indicators in a community-based comprehensive smoking cessation program in 50 urban, low- and middle-income African-American smokers. The intervention was an intensive six-session group program delivered in the community and a one-month supply of the transdermal nicotine patch.

Results showed 74% of enrolled participants completed the program and 51% of participants were highly adherent to patch use guidelines. Intent-to-treat analyses revealed that 34% of participants were biochemically confirmed as having quit smoking at one month...

Nicotine Effects on Affective Response in Depression-Prone Smokers

Administrator — Wed, 27 May 2009 02:45:06 +0000

By Spring B., Cook J.W., Appelhans B., Maloney A., Richmond M., Vaughn J., Vanderveen J. and Hedeker D.

Rationale: Comorbidity between cigarette smoking and depression is thought to arise because depression-prone smokers self-administer nicotine to improve mood. Yet little evidence supports this view, and nicotine's effect on positive affect deficiency in depression remains largely unstudied.

Objectives: We hypothesized that (1) nicotine would dispel negative affect and enhance positive affect and (2) effects would be stronger for smokers vulnerable to depression, particularly during a depressed state.

Materials and methods: Regular smokers (N=165) were recruited from the community: 63 with no history of major depressive disorder (MDD), 61 with recurrent past but no current MDD, and 41 with both current and past MDD. During four sessions, participants smoked either a nicotinized (NIC+) or denicotinized (NIC-) cigarette double blind after experiencing a...

Depressive symptoms and smoking cessation after hospitalization for cardiovascular disease

Administrator — Wed, 27 May 2009 02:44:22 +0000

By Thorndike A.N., Regan S., McKool K., Pasternak R.C., Swartz S., Torres-Finnerty N., Rigotti N.A.

Background: Although smoking cessation is essential for prevention of secondary cardiovascular disease (CVD), many smokers do not stop smoking after hospitalization. Mild depressive symptoms are common during hospitalization for CVD. We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital.

Methods: This was a planned secondary analysis of data from a placebo-controlled, double-blind, randomized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD. All subjects received smoking counseling in the hospital and for 12 weeks after discharge. Depressive symptoms were measured during hospitalization with the Beck Depression Inventory (BDI), and smoking cessation was biochemically validated at 2-week, 12-week, and 1-year follow-up. The effect of depressive symptoms on smoking cessation was assessed using multiple logistic...