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      Neuropsychiatric Disease and Treatment (submit here)

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      Varenicline in the treatment of tobacco dependence

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          Abstract

          Varenicline, a partial agonist of α 4β 2 nicotinic acetylcholine receptors, is the most recently approved drug for smoking cessation. This paper reviews the outcomes of Phase 2 and Phase 3 clinical trials that assess the efficacy of varenicline in comparison to placebo and other smoking cessation pharmacotherapies, ie, sustained-release bupropion (bupropion SR) and nicotine transdermal patch. Varenicline has higher abstinence rates than placebo and the alternative active treatments at the end of standard regimen treatment periods. Significantly higher abstinence rates were also found with varenicline in comparison to both placebo and bupropion SR at the end of a 40-week non-treatment follow-up period. Varenicline typically tripled the abstinence rates compared with placebo. In addition, varenicline reduced craving and withdrawal symptoms as well as some of the positive experiences associated with smoking to a greater extent than placebo, bupropion SR, and nicotine replacement therapy (NRT). These findings are consistent with the proposed agonist/antagonist effects of varenicline. Preliminary studies assessing individual variables such as smoking dependency level and smoking reinforcement types provide justification to examine further the effects of varenicline according to these individual factors. Outcomes from such research could improve our understanding of varenicline’s mechanism of action and could ultimately help clinicians to develop individualized smoking cessation programs. Also, given varenicline’s ability to reduce the reward from smoking, it might be helpful to use it before cessation to motivate or prepare smokers for a quit attempt.

          Most cited references71

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          The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire.

          We examine and refine the Fagerström Tolerance Questionnaire (FTQ: Fagerström, 1978). The relation between each FTQ item and biochemical measures of heaviness of smoking was examined in 254 smokers. We found that the nicotine rating item and the inhalation item were unrelated to any of our biochemical measures and these two items were primary contributors to psychometric deficiencies in the FTQ. We also found that a revised scoring of time to the first cigarette of the day (TTF) and number of cigarettes smoked per day (CPD) improved the scale. We present a revision of the FTQ: the Fagerström Test for Nicotine Dependence (FTND).
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            Development of a rational scale to assess the harm of drugs of potential misuse.

            Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.
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              Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review.

              As more interventions become available for the treatment of coronary heart disease (CHD), policy makers and health practitioners need to understand the benefits of each intervention, to better determine where to focus resources. This is particularly true when a patient with CHD quits smoking. To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD. Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration). Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting. Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form. From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries. Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                April 2008
                April 2008
                : 4
                : 2
                : 353-363
                Affiliations
                [1 ]Smokers Information Centre, Fagerström Consulting AB Berga Alle 1, 25452 Helsingborg, Sweden
                [2 ]University of Vermont Burlington, Vermont, USA
                Author notes
                Correspondence: Karl Fagerström Smokers Information Centre, Fagerström Consulting AB, Berga Alle 1, 25452, Helsingborg, Sweden Tel +46 42 150650 Fax +46 42 165760 Email karl.fagerstrom@ 123456swipnet.se
                Article
                10.2147/NDT.S927
                2518383
                18728741
                19dafba8-b14b-4bd0-b6fa-7e78a859aa9b
                © 2008 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Expert Opinion

                Neurology
                varenicline,smoking cessation,nicotinic partial agonist
                Neurology
                varenicline, smoking cessation, nicotinic partial agonist

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