Article

Pharmacological interventions for smoking cessation: An overview and network meta-analysis

Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, UK, OX2 6GG.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2013; 5(5):CD009329. DOI: 10.1002/14651858.CD009329.pub2
Source: PubMed

ABSTRACT BACKGROUND: Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness. OBJECTIVES: How do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)? How do the remaining treatments compare with placebo in achieving long-term abstinence? How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits? METHODS: The overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments. We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events. MAIN RESULTS: We identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectively). Varenicline increased the odds of quitting compared with placebo (OR 2.88; 95% CredI 2.40 to 3.47). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CredI 1.29 to 1.96). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46). Cytisine (a nicotine receptor partial agonist) returned positive findings (risk ratio (RR) 3.98; 95% CI 2.01 to 7.87), without significant adverse events or SAEs. Across the 82 included and excluded bupropion trials, our estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1:1000), at about 1:1500. SAE meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59). SAE meta-analysis of 14 varenicline trials found no difference between the varenicline and placebo arms (RR 1.06; 95% CI 0.72 to 1.55), and subgroup analyses detected no significant excess of neuropsychiatric events (RR 0.53; 95% CI 0.17 to 1.67), or of cardiac events (RR 1.26; 95% CI 0.62 to 2.56). Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone. Clonidine increased the chances of quitting (RR 1.63; 95% CI 1.22 to 2.18), but this was offset by a dose-dependent rise in adverse events. Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive. Other treatments failed to demonstrate a benefit compared with placebo. Nicotine vaccines are not yet licensed for use as an aid to smoking cessation or relapse prevention. Nicobrevin's UK license is now revoked, and the manufacturers of rimonabant, taranabant and dianicline are no longer supporting the development or testing of these treatments. AUTHORS' CONCLUSIONS: NRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use. Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.

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    • "used as single agents or in combination with NRTs (Jorenby et al., 1999; Cahill et al., 2013; Smith et al., 2003). "
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    ABSTRACT: Varenicline and bupropion are commonly prescribed non-nicotine containing smoking cessation agents. Post-marketing reports suggest an increased incidence of psychiatric disturbances associated with varenicline and bupropion. However, pre-existing psychiatric disorders may confound the association between these smoking cessation agents and psychiatric disturbances. We compared the mental health status of individuals using varenicline or bupropion to that of people quitting without medication, current smokers, and non-smokers while controlling for pre-existing conditions. A cross-sectional design was used. Data were from 2006-2011 Medical Expenditure Panel Survey. Mental health status was assessed using the mental component summary (MCS) from the 12-item Short Form survey (SF-12v2), 2-item Patient Health Questionnaire (PHQ-2), and Kessler 6 Scale (K6). Differences in MCS score were compared using linear regression. Logistic regressions were used to compare positive screenings for depression using PHQ-2 and for psychological distress using K6. Of 578 use episodes, 453 (78.38%) were bupropion and 125 (21.62%) were varenicline. After adjusting for potential confounders, mental health status of varenicline users was not different from current smokers or people who quit smoking without medication, but worse than non-smokers; bupropion was strongly associated with lower mental health status relative to all groups across all three measures. Varenicline was not associated with worse mental health compared to smokers or those who quit without medication, after adjusting for pre-existing psychiatric disorders. Bupropion was associated with worse mental health status than smokers, former smokers who quit without medication, and nonsmokers, even after adjusting for pre-existing psychiatric disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 06/2015; DOI:10.1016/j.drugalcdep.2015.06.028 · 3.28 Impact Factor
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    • "Nicotine replacement therapy (NRT) is an effective pharmacological smoking cessation treatment relative to placebo (Cahill et al., 2013). The efficacy of NRT is influenced by a number of factors, including type of NRT used, and combination versus single type use (Cahill et al., 2013). Adherence to and consumption of NRT prescription also influences efficacy; Shiffman (2007) showed that the use of more NRT lozenges was associated with better smoking cessation outcomes—each additional lozenge consumed was associated with increased odds of quitting success by 10%. "
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    ABSTRACT: While nicotine replacement therapy (NRT) is an effective pharmacological smoking cessation treatment, its efficacy is influenced by adherence to and consumption of the prescribed dose. The genetic variant rs1051730 in the nicotinic receptor gene cluster CHRNA5-A3-B4 influences smoking quantity. The aim of this study was to explore the impact of rs1051730 genotype on adherence to and consumption of NRT prescription following a smoking cessation attempt. Secondary analysis of data from a pharmacogenetic smoking cessation trial. Participants (n=448) were prescribed a daily dose of NRT for four weeks post quit attempt, and monitored during weekly clinic visits. Outcome measures were NRT prescription adherence rate (%) and average daily NRT consumption (mg) at 7- and 28-days after the quit attempt. An association between rs1051730 genotype and both outcome measures was observed at 7-days after the quit date. Each copy of the minor allele corresponded to a 2.9% decrease in adherence to prescribed NRT dose (P=0.044), and a 1.0mg decrease in daily NRT consumption (P=0.026). Adjusting for number of cigarettes smoked during this period only slightly attenuated these associations. There was no clear statistical evidence of an association between genotype and adherence or consumption at 28-days. This is the first study to evaluate the impact of rs1051730 genotype on consumption of and adherence to NRT prescription during a smoking cessation attempt. We observed an association between this variant and both outcome measures at 7-days; however, this was only moderate. These findings require replication in an independent sample. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Drug and alcohol dependence 04/2015; 165. DOI:10.1016/j.drugalcdep.2015.03.035 · 3.28 Impact Factor
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    • "Recent systematic reviews suggested that the most effective smoking cessation strategy for this patient group would be pharmacological therapy in combination with intensive counselling (Warnier et al. 2013) and face-to-face contacts yielding higher quit rates than telephone contacts (Stead & Lancaster 2012). In primary health care, where most patients with COPD are treated, low-intensity support in smoking cessation is usually employed, such as simple advice to quit, minimal intervention or telephone counselling, alone or in combination with medications (nicotine replacement therapy, bupropion or varenicline (Cahill et al. 2013). To redirect and use efficiently the limited resources of healthcare providers in outpatients' settings, it would be very useful to identify those COPD patients who might develop pressure-filled mental states, have high risk of failure during a quit attempt or even give up any plan to quit smoking after an unsuccessful attempt. "
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    ABSTRACT: AimsTo test internal consistency and factor structure of a brief instrument called Trying to Quit smoking.Background The most effective treatment for patients with chronic obstructive pulmonary disease is to quit smoking. Constant thoughts about quitting and repeated quit attempts can generate destructive feelings and make it more difficult to quit.DesignDevelopment and psychometric testing of the Trying to Quit smoking scale.Methods The Trying to Quit smoking, an instrument designed to assess pressure-filled states of mind and corresponding pressure-relief strategies, was tested among 63 Swedish patients with chronic obstructive pulmonary disease. Among these, the psychometric properties of the instrument were analysed by Exploratory Factor Analyses.ResultsFourteen items were included in the factor analyses, loading on three factors labelled: (1) development of pressure-filled mental states; (2) use of destructive pressure-relief strategies; and (3) ambivalent thoughts when trying to quit smoking. These three factors accounted for more than 80% of the variance, performed well on the Kaiser-Meyer-Olkin (KMO) test and had high internal consistency.
    12/2014; 1(1). DOI:10.1002/nop2.4
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