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      Relapse prevention interventions for smoking cessation

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          Abstract

          A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register, clinicaltrials.gov, and the ICTRP in May 2019 for studies mentioning relapse prevention or maintenance in their title, abstracts, or keywords. Randomised or quasi‐randomised controlled trials of relapse prevention interventions with a minimum follow‐up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included studies that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. We used standard methodological procedures expected by Cochrane. We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty‐eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I 2 = 82%; moderate‐certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I 2 = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I 2 = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I 2 = 0%; low‐certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I 2 = 0%; moderate‐certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I 2 = 66%; low‐certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I 2 = 0%) and at postpartum follow‐up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I 2 = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I 2 = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I 2 = 52%; moderate‐certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I 2 = 1%) from the general population. Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate‐certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low‐certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit. Do any treatments help people who have successfully quit smoking to avoid starting smoking again? Background Some people start smoking again shortly after quitting and are said to have 'relapsed'. Treatments used to help people avoid relapse usually focus on teaching the skills to cope with temptations to smoke, but can also involve extending the length of the treatment that helped them to quit, or giving additional treatment, like follow‐up calls, leaflets, or stop‐smoking medicine. We set out to see if these types of approaches can be helpful, either for people who quit on their own or with the help of treatment, or for those who quit because they were pregnant or in hospital. Study characteristics We updated our searches of research databases in May 2019. We found 81 studies that tested various ways of trying to help people who had recently quit smoking not to relapse. Five of them were new for this update. Fifty studies included people who had already quit, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty‐eight studies focused on people who needed to stop smoking for a limited period of time because they were pregnant (19 studies), in hospital (six studies), or because of military service (three studies). Most of the studies used behavioural support treatments that tried to teach people skills to cope with the urge to smoke, or followed up with additional leaflets or calls, internet or mobile phone resources, or additional counselling. Some studies tested extending the use of medicines for helping people to quit smoking, in the hope of preventing relapse. Key results The evidence we found does not support the use of behavioural treatments to help prevent relapse after quitting smoking. This result was the same in all of the different groups of people studied. The most promising treatments involved extending treatment with stop‐smoking medicine, in particular, varenicline. Extending treatment with bupropion did not appear to help and there was not enough evidence on extending treatment with nicotine replacement therapy. Certainty of the evidence For behavioural treatments, the certainty of the evidence was moderate. This is because of the diversity of results among studies. The certainty of evidence for treatments with quit‐smoking medicines varied. There was moderate‐certainty evidence for varenicline, moderate‐certainty evidence for bupropion, and low‐certainty evidence for nicotine replacement therapy (NRT), and for NRT and bupropion together. Certainty in the evidence was limited by small study sizes.

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          Most cited references196

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          Measuring inconsistency in meta-analyses.

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

            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. 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? 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. 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. 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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              Nicotine replacement therapy versus control for smoking cessation

              Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.
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                Author and article information

                Journal
                146518
                Cochrane Database of Systematic Reviews
                Wiley
                14651858
                October 28 2019
                Affiliations
                [1 ]University of Oxford; Nuffield Department of Primary Care Health Sciences; Oxford UK
                [2 ]University College London; Centre for Behaviour Change; London UK
                [3 ]University College London; Department of Behavioural Science and Health; 1-19 Torrington Place London UK WC1E 6BT
                [4 ]University College London; Health Behavior Research Centre of Cancer Research UK, Department of Epidemiology and Public Health; 2-16 Torrington Place London UK WC1E 6BT
                [5 ]Cardiff University; School of Psychology; Cardiff UK
                [6 ]Barts & The London School of Medicine and Dentistry, Queen Mary University of London; Wolfson Institute of Preventive Medicine; 55 Philpot Street London UK E1 2HJ
                Article
                10.1002/14651858.CD003999.pub6
                0e53bdc8-5acf-4612-8fb7-6099bd609fbc
                © 2019
                History

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