BACKGROUNDNicotine 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.OBJECTIVESTo determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions.SEARCH METHODSWe searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017.SELECTION CRITERIARandomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews.DATA COLLECTION AND ANALYSISScreening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model.MAIN RESULTSWe identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare.AUTHORS' CONCLUSIONSThere is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.

Background Individual counselling from a smoking cessation specialist may help smokers to make a successful attempt to stop smoking. Objectives The review addresses the following hypotheses: 1. Individual counselling is more effective than no treatment or brief advice in promoting smoking cessation. 2. Individual counselling is more effective than self‐help materials in promoting smoking cessation. 3. A more intensive counselling intervention is more effective than a less intensive intervention. Search methods We searched the Cochrane Tobacco Addiction Group Specialized Register for studies with counsel* in any field in May 2016. Selection criteria Randomized or quasi‐randomized trials with at least one treatment arm consisting of face‐to‐face individual counselling from a healthcare worker not involved in routine clinical care. The outcome was smoking cessation at follow‐up at least six months after the start of counselling. Data collection and analysis Both authors extracted data in duplicate. We recorded characteristics of the intervention and the target population, method of randomization and completeness of follow‐up. We used the most rigorous definition of abstinence in each trial, and biochemically‐validated rates where available. In analysis, we assumed that participants lost to follow‐up continued to smoke. We expressed effects as a risk ratio (RR) for cessation. Where possible, we performed meta‐analysis using a fixed‐effect (Mantel‐Haenszel) model. We assessed the quality of evidence within each study using the Cochrane 'Risk of bias' tool and the GRADE approach. Main results We identified 49 trials with around 19,000 participants. Thirty‐three trials compared individual counselling to a minimal behavioural intervention. There was high‐quality evidence that individual counselling was more effective than a minimal contact control (brief advice, usual care, or provision of self‐help materials) when pharmacotherapy was not offered to any participants (RR 1.57, 95% confidence interval (CI) 1.40 to 1.77; 27 studies, 11,100 participants; I2 = 50%). There was moderate‐quality evidence (downgraded due to imprecision) of a benefit of counselling when all participants received pharmacotherapy (nicotine replacement therapy) (RR 1.24, 95% CI 1.01 to 1.51; 6 studies, 2662 participants; I2 = 0%). There was moderate‐quality evidence (downgraded due to imprecision) for a small benefit of more intensive counselling compared to brief counselling (RR 1.29, 95% CI 1.09 to 1.53; 11 studies, 2920 participants; I2 = 48%). None of the five other trials that compared different counselling models of similar intensity detected significant differences. Authors' conclusions There is high‐quality evidence that individually‐delivered smoking cessation counselling can assist smokers to quit. There is moderate‐quality evidence of a smaller relative benefit when counselling is used in addition to pharmacotherapy, and of more intensive counselling compared to a brief counselling intervention.

This article examines the role of doctors in assisting patients who smoke to quit, using evidence from Cochrane systematic reviews of randomised trials. Doctors may help such patients by providing advice, referring patients for counselling and support and by offering pharmacological therapy. Complementary therapies used for smoking cessation include hypnotherapy and acupuncture, but there is a lack of evidence that these interventions have a specific effect in aiding cessation. The number needed to treat (NNT) for simple advice to unselected smokers is 50 - 120. Based on a median no-treatment clinical trial quit rate of 7.5%, the NNT for nicotine replacement therapy is 23 (95% CI 20 to 27), for the antidepressant Bupropion 18 (95% CI 14 to 23), and for the nicotinic partial agonist Varenicline 10 (95% CI 7 to 14). These numbers compare favourably with other preventive healthcare interventions. There remains wide variations in the extent to which these interventions are available in different healthcare systems.

Background Although smoking cessation is currently the only guaranteed way to reduce the harm caused by tobacco smoking, a reasonable secondary tobacco control approach may be to try and reduce the harm from continued tobacco use amongst smokers unable or unwilling to quit. Possible approaches to reduce the exposure to toxins from smoking include reducing the amount of tobacco used, and using less toxic products, such as pharmaceutical, nicotine and potential reduced-exposure tobacco products (PREPs), as an alternative to cigarettes. Objectives To assess the effects of interventions intended to reduce the harm to health of continued tobacco use, we considered the following specific questions: do interventions intended to reduce harm have an effect on long-term health status?; do they lead to a reduction in the number of cigarettes smoked?; do they have an effect on smoking abstinence?; do they have an effect on biomarkers of tobacco exposure?; and do they have an effect on biomarkers of damage caused by tobacco? Search methods We searched the Cochrane Tobacco Addiction Group Trials Register (CRS) on the 21st October 2015, using free-text and MeSH terms for harm reduction, smoking reduction and cigarette reduction. Selection criteria Randomized or quasi-randomized controlled trials of interventions to reduce the amount smoked, or to reduce harm from smoking by means other than cessation. We include studies carried out in smokers with no immediate desire to quit all tobacco use. Primary outcomes were change in cigarette consumption, smoking cessation and any markers of damage or benefit to health, measured at least six months from the start of the intervention. Data collection and analysis We assessed study eligibility for inclusion using standard Cochrane methods. We pooled trials with similar interventions and outcomes (> 50% reduction in cigarettes a day (CPD) and long-term smoking abstinence), using fixed-effect models. Where it was not possible to meta-analyse data, we summarized findings narratively. Main results Twenty-four trials evaluated interventions to help those who smoke to cut down the amount smoked or to replace their regular cigarettes with PREPs, compared to placebo, brief intervention, or a comparison intervention. None of these trials directly tested whether harm reduction strategies reduced the harms to health caused by smoking. Most trials (14/24) tested nicotine replacement therapy (NRT) as an intervention to assist reduction. In a pooled analysis of eight trials, NRT significantly increased the likelihood of reducing CPD by at least 50% for people using nicotine gum or inhaler or a choice of product compared to placebo (risk ratio (RR) 1.75, 95% confidence interval (CI) 1.44 to 2.13; 3081 participants). Where average changes from baseline were compared for different measures, carbon monoxide (CO) and cotinine generally showed smaller reductions than CPD. Use of NRT versus placebo also significantly increased the likelihood of ultimately quitting smoking (RR 1.87, 95% CI 1.43 to 2.44; 8 trials, 3081 participants; quality of the evidence: low). Two trials comparing NRT and behavioural support to brief advice found a significant effect on reduction, but no significant effect on cessation. We found one trial investigating each of the following harm reduction intervention aids: bupropion, varenicline, electronic cigarettes, snus, plus another of nicotine patches to facilitate temporary abstinence. The evidence for all five intervention types was therefore imprecise, and it is unclear whether or not these aids increase the likelihood of smoking reduction or cessation. Two trials investigating two different types of behavioural advice and instructions on reducing CPD also provided imprecise evidence. Therefore, the evidence base for this comparison is inadequate to support the use of these types of behavioural advice to reduce smoking. Four studies of PREPs (cigarettes with reduced levels of tar, carbon and nicotine, and in one case delivered using an electronically-heated cigarette smoking system) showed some reduction in exposure to some toxicants, but it is unclear whether this would substantially alter the risk of harm. We judged the included studies to be generally at a low or unclear risk of bias; however, there were some ratings of high risk, due to a lack of blinding and the potential for detection bias. Using the GRADE system, we rated the overall quality of the evidence for our cessation outcomes as 'low' or 'very low', due to imprecision and indirectness. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. Authors' conclusions People who do not wish to quit can be helped to cut down the number of cigarettes they smoke and to quit smoking in the long term, using NRT, despite original intentions not to do so. However, we rated the evidence contributing to the cessation outcome for NRT as 'low' by GRADE standards. There is a lack of evidence to support the use of other harm reduction aids to reduce the harm caused by continued tobacco smoking. This could simply be due to the lack of high-quality studies (our confidence in cessation outcomes for these aids is rated 'low' or 'very low' due to imprecision by GRADE standards), meaning that we may have missed a worthwhile effect, or due to a lack of effect on reduction or quit rates. It is therefore important that more high-quality RCTs are conducted, and that these also measure the long-term health effects of treatments.

Source Citation Thomas KH, Martin RM, Knipe DW, Higgins JP, Gunnell D. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ. 2015;350:h1109. 25767129

BACKGROUND:Effective pharmacotherapies are available to help people who are trying to stop smoking, but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further. OBJECTIVES:To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. SEARCH METHODS:We searched the Cochrane Tobacco Addiction Group Specialised Register in May 2015 for records with any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline that evaluated the addition of personal support or compared two or more intensities of behavioural support. SELECTION CRITERIA:Randomized or quasi-randomized controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount of behavioural support. The intervention condition had to involve person-to-person contact. The control condition could receive less intensive personal contact, or just written information. We did not include studies that used a contact-matched control to evaluate differences between types or components of support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS:One author prescreened search results and two authors agreed inclusion or exclusion of potentially relevant trials. One author extracted data and another checked them.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically-validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. MAIN RESULTS:Forty-seven studies met the inclusion criteria with over 18,000 participants in the relevant arms. There was little evidence of statistical heterogeneity (I² = 18%) so we pooled all studies in the main analysis. There was evidence of a small but statistically significant benefit from more intensive support (RR 1.17, 95% CI 1.11 to 1.24) for abstinence at longest follow-up. All but four of the included studies provided four or more sessions of support to the intervention group. Most trials used NRT. We did not detect significant effects for studies where the pharmacotherapy was nortriptyline (two trials) or varenicline (one trial), but this reflects the absence of evidence.In subgroup analyses, studies that provided at least four sessions of personal contact for the intervention and no personal contact for the control had slightly larger estimated effects (RR 1.25, 95% CI 1.08 to 1.45; 6 trials, 3762 participants), although a formal test for subgroup differences was not significant. Studies where all intervention counselling was via telephone (RR 1.28, 95% CI 1.17 to 1.41; 6 trials, 5311 participants) also had slightly larger effects, and the test for subgroup differences was significant, but this subgroup analysis was not prespecified. In this update, the benefit of providing additional behavioural support was similar for the subgroup of trials in which all participants, including controls, had at least 30 minutes of personal contact (RR 1.18, 95% CI 1.06 to 1.32; 21 trials, 5166 participants); previously the evidence of benefit in this subgroup had been weaker. This subgroup was not prespecified and a test for subgroup differences was not significant. We judged the quality of the evidence to be high, using the GRADE approach. We judged a small number of trials to be at high risk of bias on one or more domains, but findings were not sensitive to their exclusion. AUTHORS' CONCLUSIONS:Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 25%, based on a pooled estimate from 47 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support.

Objectives This meta-analysis sought to evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. Post-treatment abstinence was examined as a secondary outcome and effects on withdrawal symptoms, craving and reduced consumption were also explored. Design The search strategy for this meta-analysis included clinical trials (published and unpublished data) in the Cochrane Tobacco Addiction Group Specialized Register and MEDLINE. Participants Adult smokers. Interventions We included randomised trials comparing opioid antagonists to placebo or an alternative therapy for smoking cessation and reported data on abstinence for a minimum of 6 months. Primary and secondary outcome measures Outcomes included smoking abstinence at long-term follow-up (primary); abstinence at end of treatment (secondary); and effects on withdrawal, craving and smoking consumption (exploratory). Results 8 trials with a total of 1213 participants were included. Half the trials examined the benefit of adding naltrexone versus placebo to nicotine replacement therapy (NRT). There was no significant difference between naltrexone and placebo alone (relative risk (RR) 1.00; 95% CI 0.66 to 1.51) or as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30), with an overall pooled estimate of RR 0.97; 95% CI 0.76 to 1.24. Findings for naltrexone effects on withdrawal, craving and reduced smoking were equivocal. Conclusions The findings indicate no beneficial effect of naltrexone alone or as an adjunct to NRT on short-term or long-term smoking abstinence. While further trials may narrow the confidence limits, they are unlikely to appreciably alter the conclusion.

CLINICAL QUESTION:Among the 3 first-line smoking cessation treatments (nicotine replacement therapy [NRT], bupropion, and varenicline), which is most effective in helping people who smoke achieve and maintain abstinence from smoking for at least 6 months, and what serious adverse events are associated with each?BOTTOM LINE:Higher rates of smoking cessation were associated with NRT (17.6%) and bupropion (19.1%) compared with placebo (10.6%). Varenicline (27.6%) and combination NRT (31.5%) (eg, patch plus inhaler) were most effective for achieving smoking cessation. None of the therapies was associated with an increased rate of serious adverse events.

AIMS The Cochrane Collaboration is an international not-for profit organization which produces and disseminates systematic reviews. This paper is the second in a series of annual updates of Cochrane reviews on tobacco addiction interventions, covering new and updated reviews from 2013. METHODS In 2013, the Group published two new reviews and updated 11 others. This update summarizes and comments on these reviews as well as on a review of psychosocial interventions for smoking cessation in pregnant women, and presents pooled results from reviews of cessation interventions. RESULTS New reviews in 2013 found: low-quality evidence that behavioural interventions with mood management components could significantly increase long-term quit rates in people with current [risk ratio (RR) = 1.47, 95% confidence interval (CI) = 1.13-1.92) and past (RR = 1.41, 95% CI = 1.13-1.77] depression; evidence from network meta-analysis that varenicline and combined forms of nicotine replacement therapy (NRT) are associated with higher quit rates than bupropion or single-form NRT (varenicline versus single-form NRT odds ratio (OR) = 1.57, 95% credibility interval (CredI) = 1.29-1.91; versus bupropion OR = 1.59, 95% CredI = 1.29-1.96); and no evidence of a significant increase in serious adverse events in trial participants randomized to varenicline or bupropion when compared to placebo controls. New evidence emerging from updated reviews suggests that counselling interventions can increase quit rates in pregnant women and that school-based smoking programmes with social competence curricula can lead to a significant reduction in uptake of smoking at more than a year. Updated reviews also suggested that naltrexone, selective serotonin re-uptake inhibitors and St John's wort do not have a significant effect on long-term smoking cessation. CONCLUSIONS Cochrane systematic review evidence from 2013 suggests that adding mood management to behavioural support may improve cessation outcomes in smokers with current or past depression and strengthens evidence for previous conclusions, including the safety of varenicline and bupropion and the benefits of behavioural support for smoking cessation in pregnancy.

A 56 year old woman presents with a history of fullness in her ears and reduced hearing, which has persisted for three weeks. She often hears clicking when she swallows. The eustachian tube is a cartilaginous and bony tube providing a connection between the nasopharynx and the middle ear. At rest, the eustachian tube is closed, but it opens on swallowing, yawning, sneezing, and the Valsalva manoeuvre due to contraction of palatine muscles. When the eustachian tube opens it facilitates equalisation of pressures between the external environment and the middle ear by allowing a bolus of air to pass through. Dysfunction of the eustachian tube results in development of negative pressures within the middle ear, leading to transudation of fluid and a pro-inflammatory response. Consequentially, eustachian tube dysfunction is an important component of pathology of the middle ear, particularly acute otitis media and otitis media with effusion. ### History Feeling of fullness in the ears— Eustachian tube dysfunction classically presents with a feeling of fullness in the ear, often associated with hearing loss. Eustachian tube dysfunction should be a diagnosis of exclusion as ear fullness can be the presenting feature in a wide variety of clinical entities of the external, middle, and inner ears. There is a requirement for …

BackgroundMany smokers give up smoking on their own, but materials giving advice and information may help them and increase the number who quit successfully.ObjectivesThe aims of this review were to determine: the effectiveness of different forms of print-based self-help materials, compared with no treatment and with other minimal contact strategies; the effectiveness of adjuncts to print-based self help, such as computer-generated feedback, telephone hotlines and pharmacotherapy; and the effectiveness of approaches tailored to the individual compared with non-tailored materials.Search methodsWe searched the Cochrane Tobacco Addiction Group trials register. Date of the most recent search April 2014.Selection criteriaWe included randomized trials of smoking cessation with follow-up of at least six months, where at least one arm tested a print-based self-help intervention. We defined self help as structured programming for smokers trying to quit without intensive contact with a therapist.Data collection and analysisWe extracted data in duplicate on the participants, the nature of the self-help materials, the amount of face-to-face contact given to intervention and to control conditions, outcome measures, method of randomization, and completeness of follow-up.The main outcome measure was abstinence from smoking after at least six months follow-up in people smoking at baseline. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates when available. Where appropriate, we performed meta-analysis using a fixed-effect model.Main resultsWe identified 74 trials which met the inclusion criteria. Many study reports did not include sufficient detail to judge risk of bias for some domains. Twenty-eight studies ( 38%) were judged at high risk of bias for one or more domains but the overall risk of bias across all included studies was judged to be moderate, and unlikely to alter the conclusions.Thirty-four trials evaluated the effect of standard, non-tailored self-helpmaterials. Pooling 11 of these trials in which there was no face-to-face contact and provision of structured self-help materials was compared to no intervention gave an estimate of benefit that just reached statistical significance (n = 13,241, risk ratio [RR] 1.19, 95% confidence interval [CI] 1.04 to 1.37). This analysis excluded two trials with strongly positive outcomes that introduced significant heterogeneity. Six further trials without face-to-face contact in which the control group received alternative written materials did not show evidence for an effect of the smoking self-help materials (n = 7023, RR 0.88, 95% CI 0.74 to 1.04). When these two subgroups were pooled, there was no longer evidence for a benefit of standard structured materials (n = 20,264, RR 1.06, 95% CI 0.95 to 1.18). We failed to find evidence of benefit from providing standard self-help materials when there was brief contact with all participants (5 trials, n = 3866, RR 1.17, 95% CI 0.96 to 1.42), or face-to-face advice for all participants (11 trials, n = 5365, RR 0.97, 95% CI 0.80 to 1.18).Thirty-one trials offered materials tailored for the characteristics of individual smokers, with controls receiving either no materials, or stage matched or non-tailored materials. Most of the trials used more than one mailing. Pooling these showed a benefit of tailored materials (n = 40,890, RR 1.28, 95% CI 1.18 to 1.37) with moderate heterogeneity (I-2 = 32%). The evidence is strongest for the subgroup of nine trials in which tailored materials were compared to no intervention (n = 13,437, RR 1.35, 95% CI 1.19 to 1.53), but also supports tailored materials as more helpful than standard materials. Part of this effect could be due to the additional contact or assessment required to obtain individual data, since the subgroup of 10 trials where the number of contacts was matched did not detect an effect (n = 11,024, RR 1.06, 95% CI 0.94 to 1.20). In two trials including a direct comparison between tailored materials and brief advice from a health care provider, there was no evidence of a difference, but confidence intervals were wide (n = 2992, RR 1.13, 95% CI 0.86 to 1.49).Only four studies evaluated self-help materials as an adjunct to nicotine replacement therapy, with no evidence of additional benefit (n = 2291, RR 1.05, 95% CI 0.88 to 1.25). A small number of other trials failed to detect benefits from using additional materials or targeted materials, or to find differences between different self-help programmes.Authors' conclusionsStandard, print-based self-help materials increase quit rates compared to no intervention, but the effect is likely to be small. We did not find evidence that they have an additional benefit when used alongside other interventions such as advice from a healthcare professional, or nicotine replacement therapy. There is evidence that materials that are tailored for individual smokers are more effective than non-tailored materials, although the absolute size of effect is still small. Available evidence tested self-help interventions in high income countries; further research is needed to investigate their effect in contexts where more intensive support is not available.

ACP Journal Club17 June 2014In pregnant smokers, the nicotine patch did not increase abstinence or birthweight more than placeboTim Lancaster, MDTim Lancaster, MDNuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, UK (T.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-160-12-201406170-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBerlin I, Grange G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622. https://pubmed.ncbi.nlm.nih.gov/24627552Clinical Impact RatingsGIM/FP/GP: Author, Article, and Disclosure InformationAuthors: Tim Lancaster, MDAffiliations: Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, UK (T.L.)This article was published at Annals.org on 3 June 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNicotine replacement therapy versus control for smoking cessationA systematic review of possible serious adverse health effects of nicotine replacement therapy 17 June 2014Volume 160, Issue 12Page: JC11KeywordsBirthInfantsNicotinePatientsPopulation statisticsPregnancyResearch laboratoriesSalivaSmoking cessationStillbirths ePublished: 17 June 2014 Issue Published: 17 June 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Mini-ReviewTubenventilationsstörungen beim ErwachsenenRhona Sproat, Christopher Burgess, Tim Lancaster, and Pablo Martinez-DevesaRhona Sproat Ear, Nose, and Throat Department, John Radcliffe Hospital, Oxford OX3 9DU, Grossbritannien Search for more papers by this author, Christopher Burgess Ear, Nose, and Throat Department, John Radcliffe Hospital, Oxford OX3 9DU, Grossbritannien1 Search for more papers by this author, Tim Lancaster Jericho Health Centre – Primary Care, Oxford, Grossbritannien Search for more papers by this author, and Pablo Martinez-Devesa Ear, Nose, and Throat Department, John Radcliffe Hospital, Oxford OX3 9DU, Grossbritannien Search for more papers by this authorPublished Online:October 10, 2014https://doi.org/10.1024/1661-8157/a001807PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreFiguresReferencesRelatedDetails Volume 103Issue 21October 2014ISSN: 1661-8157eISSN: 1661-8165 InformationPraxis (2014), 103, pp. 1275-1277 https://doi.org/10.1024/1661-8157/a001807.© 2014Hogrefe AGPDF download

BackgroundSmoking 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.ObjectivesHow 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?MethodsThe 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 resultsWe 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' conclusionsNRT, 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.