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1.
Med Teach ; : 1-5, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37963426

ABSTRACT

A good curriculum vitae (CV) highlights medical educators' academic achievements and supports their professional goals. Many faculty struggle with timely updates and strategic formatting. These twelve tips will help medical educators optimize their CV to best showcase their strengths and accomplishments. The first three tips outline a process: identify a system to collect potential entries and schedule regular time for updates. Tips four and five detail how to tailor traditional CV formatting to best describe the work of medical educators. The next few tips offer concrete strategies and examples of CV entries to consider for inclusion. The remaining tips remind faculty to ask for help from colleagues, who can share a sample CV and identify overlooked activities. Our intention is to transform a task that can be burdensome into a process that seamlessly captures the breadth of our work as medical educators and allows for introspection and growth.

4.
MedEdPORTAL ; 18: 11211, 2022.
Article in English | MEDLINE | ID: mdl-35136835

ABSTRACT

INTRODUCTION: Medical students experience burnout, depersonalization, and decreases in empathy throughout medical training. My Life, My Story (MLMS) is a narrative medicine project that aims to combat these adverse outcomes by teaching students to interview patients about their life story, with the goal of improving patient-centered care competencies, such as empathy. METHODS: The MLMS project was started in the Veterans Affairs (VA) system and has since spread to dozens of VA sites. We adapted and integrated this project into the Warren Alpert Medical School of Brown University curriculum. As part of the required curriculum, first- and third-year medical students participated in a life story interview with a community-based volunteer or a patient in the inpatient hospital setting, transcribed the story, and reviewed the written story with the patient. We assessed student perceptions of the project, changes in empathy, and changes in burnout symptoms. RESULTS: A total of 240 students participated in this project. Students spent an average of 70.7 minutes interviewing patients. A majority of the students believed MLMS was a good use of time (77%), fostered connection with patients (79%), and was effective in recognizing patients' thoughts and feelings (69%). DISCUSSION: To our knowledge, this is one of the first life story interview interventions to be implemented into a required medical school curriculum and outside the VA setting. MLMS may assist students in improving clinical empathy skills and create a structure for medical trainees to better understand their patients.


Subject(s)
Students, Medical , Curriculum , Empathy , Humans , Patient-Centered Care , Schools, Medical
5.
Cochrane Database Syst Rev ; 11: CD004986, 2021 11 30.
Article in English | MEDLINE | ID: mdl-34847244

ABSTRACT

This review has been withdrawn because it has been superceded by the Cochrane Review of Competitions for smoking cessation.


Subject(s)
Smoking Cessation , Health Promotion , Humans , Motivation
8.
Cochrane Database Syst Rev ; (5): CD006103, 2016 May 09.
Article in English | MEDLINE | ID: mdl-27158893

ABSTRACT

BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). OBJECTIVES: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development.We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. AUTHORS' CONCLUSIONS: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.Future trials of cytisine may test extended regimens and more intensive behavioural support.


Subject(s)
Alkaloids/therapeutic use , Azepines/therapeutic use , Benzazepines/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Nicotinic Agonists/therapeutic use , Smoking Cessation/methods , Varenicline/therapeutic use , Alkaloids/adverse effects , Azepines/adverse effects , Azocines/adverse effects , Azocines/therapeutic use , Benzazepines/adverse effects , Bupropion/therapeutic use , Counseling/methods , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , Nicotine/adverse effects , Nicotine/antagonists & inhibitors , Nicotinic Agonists/adverse effects , Quinolizines/adverse effects , Quinolizines/therapeutic use , Randomized Controlled Trials as Topic , Smoking/drug therapy , Substance Withdrawal Syndrome/prevention & control
10.
Cochrane Database Syst Rev ; (5): CD004307, 2015 May 18.
Article in English | MEDLINE | ID: mdl-25983287

ABSTRACT

BACKGROUND: Material or financial incentives are widely used in an attempt to precipitate or reinforce behaviour change, including smoking cessation. They operate in workplaces, in clinics and hospitals, and to a lesser extent within community programmes. In this third update of our review we now include trials conducted in pregnant women, to reflect the increasing activity and resources now targeting this high-risk group of smokers. OBJECTIVES: To determine whether incentives and contingency management programmes lead to higher long-term quit rates. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, with additional searches of MEDLINE, EMBASE, CINAHL and PsycINFO. The most recent searches were in December 2014, although we also include two trials published in 2015. SELECTION CRITERIA: We considered randomised controlled trials, allocating individuals, workplaces, groups within workplaces, or communities to experimental or control conditions. We also considered controlled studies with baseline and post-intervention measures. We include studies in a mixed-population setting (e.g. community-, work-, institution-based), and also, for this update, trials in pregnant smokers. DATA COLLECTION AND ANALYSIS: One author (KC) extracted data and a second (JH-B) checked them. We contacted study authors for additional data where necessary. The main outcome measure in the mixed-population studies was abstinence from smoking at longest follow-up, and at least six months from the start of the intervention. In the trials of pregnant smokers abstinence was measured at the longest follow-up, and at least to the end of the pregnancy. MAIN RESULTS: Twenty-one mixed-population studies met our inclusion criteria, covering more than 8400 participants. Ten studies were set in clinics or health centres, one in Thai villages served by community health workers, two in academic institutions, and the rest in worksites. All but six of the trials were run in the USA. The incentives included lottery tickets or prize draws, cash payments, vouchers for goods and groceries, and in six trials the recovery of money deposited by those taking part. The odds ratio (OR) for quitting with incentives at longest follow-up (six months or more) compared with controls was 1.42 (95% confidence interval (CI) 1.19 to 1.69; 17 trials, [20 comparisons], 7715 participants). Only three studies demonstrated significantly higher quit rates for the incentives group than for the control group at or beyond the six-month assessment: One five-arm USA trial compared rewards- and deposit-based interventions at individual and group level, with incentives available up to USD 800 per quitter, and demonstrated a quit rate in the rewards groups of 8.1% at 12 months, compared with 4.7% in the deposits groups. A direct comparison between the rewards-based and the deposit-based groups found a benefit for the rewards arms, with an OR at 12 months of 1.76 (95% CI 1.22 to 2.53; 2070 participants). Although more people in this trial accepted the rewards programmes than the deposit programmes, the proportion of quitters in each group favoured the deposit-refund programme. Another USA study rewarded both participation and quitting up to USD 750, and achieved sustained quit rates of 9.4% in the incentives group compared with 3.6% for the controls. A deposit-refund trial in Thailand also achieved significantly higher quit rates in the intervention group (44.2%) compared with the control group (18.8%), but uptake was relatively low, at 10.5%. In the remaining trials, there was no clear evidence that participants who committed their own money to the programme did better than those who did not, or that contingent rewards enhanced success rates over fixed payment schedules. We rated the overall quality of the older studies as low, but with later trials (post-2000) more likely to meet current standards of methodology and reporting.Eight of nine trials with usable data in pregnant smokers (seven conducted in the USA and one in the UK) delivered an adjusted OR at longest follow-up (up to 24 weeks post-partum) of 3.60 (95% CI 2.39 to 5.43; 1295 participants, moderate-quality studies) in favour of incentives. Three of the trials demonstrated a clear benefit for contingent rewards; one delivered monthly vouchers to confirmed quitters and to their designated 'significant other supporter', achieving a quit rate in the intervention group of 21.4% at two months post-partum, compared with 5.9% among the controls. Another trial offered a scaled programme of rewards for the percentage of smoking reduction achieved over the course of the 12-week intervention, and achieved an intervention quit rate of 31% at six weeks post-partum, compared with no quitters in the control group. The largest (UK-based) trial provided intervention quitters with up to GBP 400-worth of vouchers, and achieved a quit rate of 15.4% at longest follow-up, compared to the control quit rate of 4%. Four trials confirmed that payments made to reward a successful quit attempt (i.e. contingent), compared to fixed payments for attending the antenatal appointment (non-contingent), resulted in higher quit rates. Front-loading of rewards to counteract early withdrawal symptoms made little difference to quit rates. AUTHORS' CONCLUSIONS: Incentives appear to boost cessation rates while they are in place. The two trials recruiting from work sites that achieved sustained success rates beyond the reward schedule concentrated their resources into substantial cash payments for abstinence. Such an approach may only be feasible where independently-funded smoking cessation programmes are already available, and within a relatively affluent and educated population. Deposit-refund trials can suffer from relatively low rates of uptake, but those who do sign up and contribute their own money may achieve higher quit rates than reward-only participants. Incentive schemes conducted among pregnant smokers improved the cessation rates, both at the end-of-pregnancy and post-partum assessments. Current and future research might continue to explore the scale, loading and longevity of possible cash or voucher reward schedules, within a variety of smoking populations.


Subject(s)
Motivation , Reward , Smoking Cessation/psychology , Female , Health Facilities , Health Promotion/methods , Humans , Male , Pregnancy , Randomized Controlled Trials as Topic , Smoking Cessation/methods , Workplace
11.
Addiction ; 109(9): 1414-25, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24995905

ABSTRACT

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.


Subject(s)
Behavior Therapy/methods , Counseling/methods , Smoking Cessation/methods , Tobacco Use Cessation Devices , Tobacco Use Disorder/therapy , Antidepressive Agents, Second-Generation/therapeutic use , Benzazepines/therapeutic use , Bupropion/therapeutic use , Female , Humans , Male , Nicotinic Agonists/therapeutic use , Pregnancy , Pregnancy Complications/therapy , Quinoxalines/therapeutic use , School Health Services , Treatment Outcome , Varenicline
12.
Cochrane Database Syst Rev ; (2): CD003440, 2014 Feb 26.
Article in English | MEDLINE | ID: mdl-24570145

ABSTRACT

BACKGROUND: The workplace has potential as a setting through which large groups of people can be reached to encourage smoking cessation. OBJECTIVES: 1. To categorize workplace interventions for smoking cessation tested in controlled studies and to determine the extent to which they help workers to stop smoking.2. To collect and evaluate data on costs and cost effectiveness associated with workplace interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register (July 2013), MEDLINE (1966 - July 2013), EMBASE (1985 - June 2013), and PsycINFO (to June 2013), amongst others. We searched abstracts from international conferences on tobacco and the bibliographies of identified studies and reviews for additional references. SELECTION CRITERIA: We selected interventions conducted in the workplace to promote smoking cessation. We included only randomized and quasi-randomized controlled trials allocating individuals, workplaces, or companies to intervention or control conditions. DATA COLLECTION AND ANALYSIS: One author extracted information relating to the characteristics and content of all kinds of interventions, participants, outcomes and methods of the studies, and a second author checked them. For this update we have conducted meta-analyses of the main interventions, using the generic inverse variance method to generate odds ratios and 95% confidence intervals. MAIN RESULTS: We include 57 studies (61 comparisons) in this updated review. We found 31 studies of workplace interventions aimed at individual workers, covering group therapy, individual counselling, self-help materials, nicotine replacement therapy, and social support, and 30 studies testing interventions applied to the workplace as a whole, i.e. environmental cues, incentives, and comprehensive programmes. The trials were generally of moderate to high quality, with results that were consistent with those found in other settings. Group therapy programmes (odds ratio (OR) for cessation 1.71, 95% confidence interval (CI) 1.05 to 2.80; eight trials, 1309 participants), individual counselling (OR 1.96, 95% CI 1.51 to 2.54; eight trials, 3516 participants), pharmacotherapies (OR 1.98, 95% CI 1.26 to 3.11; five trials, 1092 participants), and multiple intervention programmes aimed mainly or solely at smoking cessation (OR 1.55, 95% CI 1.13 to 2.13; six trials, 5018 participants) all increased cessation rates in comparison to no treatment or minimal intervention controls. Self-help materials were less effective (OR 1.16, 95% CI 0.74 to 1.82; six trials, 1906 participants), and two relapse prevention programmes (484 participants) did not help to sustain long-term abstinence. Incentives did not appear to improve the odds of quitting, apart from one study which found a sustained positive benefit. There was a lack of evidence that comprehensive programmes targeting multiple risk factors reduced the prevalence of smoking. AUTHORS' CONCLUSIONS: 1. We found strong evidence that some interventions directed towards individual smokers increase the likelihood of quitting smoking. These include individual and group counselling, pharmacological treatment to overcome nicotine addiction, and multiple interventions targeting smoking cessation as the primary or only outcome. All these interventions show similar effects whether offered in the workplace or elsewhere. Self-help interventions and social support are less effective. Although people taking up these interventions are more likely to stop, the absolute numbers who quit are low.2. We failed to detect an effect of comprehensive programmes targeting multiple risk factors in reducing the prevalence of smoking, although this finding was not based on meta-analysed data. 3. There was limited evidence that participation in programmes can be increased by competitions and incentives organized by the employer, although one trial demonstrated a sustained effect of financial rewards for attending a smoking cessation course and for long-term quitting. Further research is needed to establish which components of this trial contributed to the improvement in success rates.4. Further research would be valuable in low-income and developing countries, where high rates of smoking prevail and smoke-free legislation is not widely accepted or enforced.


Subject(s)
Smoking Cessation/methods , Smoking Prevention , Workplace , Counseling , Humans , Psychotherapy, Group , Randomized Controlled Trials as Topic , Social Support , Tobacco Use Cessation Devices
13.
JAMA ; 311(2): 193-4, 2014 Jan 08.
Article in English | MEDLINE | ID: mdl-24399558

ABSTRACT

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.


Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Benzazepines/therapeutic use , Bupropion/therapeutic use , Nicotinic Agonists/therapeutic use , Quinoxalines/therapeutic use , Smoking Cessation/methods , Tobacco Use Cessation Devices , Humans
14.
Cochrane Database Syst Rev ; (1): CD000031, 2014 Jan 08.
Article in English | MEDLINE | ID: mdl-24402784

ABSTRACT

BACKGROUND: There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction. OBJECTIVES: The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: Twenty-four new trials were identified since the 2009 update, bringing the total number of included trials to 90. There were 65 trials of bupropion and ten trials of nortriptyline, with the majority at low or unclear risk of bias. There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76). There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit. Based on a limited amount of data from direct comparisons, bupropion and nortriptyline appear to be equally effective and of similar efficacy to NRT (bupropion versus nortriptyline 3 trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N = 4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline and NRT). Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (N = 1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant increase in the rate of serious adverse events amongst participants taking bupropion, though the confidence interval only narrowly missed statistical significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation.There was no evidence of a significant effect for selective serotonin reuptake inhibitors on their own (RR 0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1 sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70, 95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5 selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22, 95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N = 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N = 120, RR 0.70, 95% CI 0.24 to 2.07). AUTHORS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Evidence also suggests that bupropion is less effective than varenicline, but further research is needed to confirm this finding. Evidence suggests that neither selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase inhibitors aid cessation.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Smoking Cessation/methods , Smoking/drug therapy , Anti-Anxiety Agents/adverse effects , Antidepressive Agents/adverse effects , Bupropion/therapeutic use , Humans , Nortriptyline/therapeutic use , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/therapeutic use , Smoking/psychology , Smoking Cessation/psychology , Tobacco Use Cessation Devices
15.
Addiction ; 108(10): 1711-21, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23834141

ABSTRACT

BACKGROUND AND AIMS: The Cochrane Collaboration is an international not-for-profit organization which produces and disseminates systematic reviews of health-care interventions. This paper is the first in a series of annual updates of Cochrane reviews on tobacco addiction interventions. It also provides an up-to-date overview of review findings in this area to date and summary statistics for cessation reviews in which meta-analyses were conducted. METHODS: In 2012, the Group published seven new reviews and updated 13 others. This update summarizes and comments on these reviews. It also summarizes key findings from all the other reviews in this area. RESULTS: New reviews in 2012 found that in smokers using pharmacotherapy, behavioural support improves success rates [risk ratio (RR) 1.16, 95% confidence interval (CI) = 1.09-1.24], and that combining behavioural support and pharmacotherapy aids cessation (RR 1.82, 95% CI = 1.66-2.00). Updated reviews established mobile phones as potentially helpful in aiding cessation (RR 1.71, 95% CI = 1.47-1.99), found that cytisine (RR 3.98, 95% CI = 2.01-7.87) and low-dose varenicline (RR 2.09, 95% CI = 1.56-2.78) aid smoking cessation, and found that training health professionals in smoking cessation improves patient cessation rates (RR 1.60, 95% CI = 1.26-2.03). The updated reviews confirmed the benefits of nicotine replacement therapy, standard dose varenicline and providing cessation treatment free of charge. Lack of demonstrated efficacy remained for partner support, expired-air carbon monoxide feedback and lung function feedback. CONCLUSIONS: Cochrane systematic review evidence for the first time establishes the efficacy of behavioural support over and above pharmacotherapy, as well as the efficacy of cytisine, mobile phone technology, low-dose varenicline and health professional training in promoting smoking cessation.


Subject(s)
Behavior, Addictive/therapy , Meta-Analysis as Topic , Review Literature as Topic , Smoking Cessation/methods , Smoking/therapy , Tobacco Use Disorder/therapy , Alkaloids/therapeutic use , Azocines/therapeutic use , Behavior Therapy/methods , Benzazepines/therapeutic use , Humans , Nicotinic Agonists/therapeutic use , Quinolizines/therapeutic use , Quinoxalines/therapeutic use , Treatment Outcome , Varenicline
16.
Cochrane Database Syst Rev ; (6): CD004704, 2013 Jun 06.
Article in English | MEDLINE | ID: mdl-23744348

ABSTRACT

BACKGROUND: Mass media tobacco control campaigns can reach large numbers of people. Much of the literature is focused on the effects of tobacco control advertising on young people, but there are also a number of evaluations of campaigns targeting adult smokers, which show mixed results. Campaigns may be local, regional or national, and may be combined with other components of a comprehensive tobacco control policy. OBJECTIVES: To assess the effectiveness of mass media interventions in reducing smoking among adults. SEARCH METHODS: The Cochrane Tobacco Addiction Group search strategy was combined with additional searches for any studies that referred to tobacco/smoking cessation, mass media and adults. We also searched the Cochrane Register of Controlled Trials (CENTRAL) and a number of electronic databases. The last search was carried out in February 2013. SELECTION CRITERIA: Controlled trials allocating communities, regions or states to intervention or control conditions; interrupted time series. Adults, 25 years or older, who regularly smoke cigarettes. Studies which cover all adults as defined in studies were included. Mass media are defined here as channels of communication such as television, radio, newspapers, billboards, posters, leaflets or booklets intended to reach large numbers of people, and which are not dependent on person-to-person contact. The purpose of the mass media campaign must be primarily to encourage smokers to quit. They could be carried out alone or in conjunction with tobacco control programmes. The primary outcome was change in smoking behaviour. This could be reported as changes in prevalence, changes in cigarette consumption, quit rates, odds of being a smoker. DATA COLLECTION AND ANALYSIS: Two authors independently assessed all studies for inclusion criteria and for study quality. One author (MB) extracted data, and a second author (LS) checked them.Results were not pooled due to heterogeneity of the included studies and are presented narratively and in table form. MAIN RESULTS: Eleven campaigns met the inclusion criteria for this review. Studies differed in design, settings, duration, content and intensity of intervention, length of follow-up, methods of evaluation and also in definitions and measures of smoking behaviour used. Among nine campaigns reporting smoking prevalence, significant decreases were observed in the California and Massachusetts statewide tobacco control campaigns compared with the rest of the USA. Some positive effects on prevalence in the whole population or in the subgroups were observed in three of the remaining seven studies. Three large-scale campaigns of the seven presenting results for tobacco consumption found statistically significant decreases. Among the seven studies presenting abstinence or quit rates, four showed some positive effect, although in one of them the effect was measured for quitting and cutting down combined. Among the three that did not show significant decreases, one demonstrated a significant intervention effect on smokers and ex-smokers combined. AUTHORS' CONCLUSIONS: There is evidence that comprehensive tobacco control programmes which include mass media campaigns can be effective in changing smoking behaviour in adults, but the evidence comes from a heterogeneous group of studies of variable methodological quality. One state-wide tobacco control programme (Massachusetts) showed positive results up to eight years after the campaign. Another (California) showed positive results during the period of adequate funding and implementation and in final evaluation since the beginning of the programme. Six of nine studies carried out in communities or regions showed some positive effects on smoking behaviour and at least one significant change in smoking prevalence (Sydney). The intensity and duration of mass media campaigns may influence effectiveness, but length of follow-up and concurrent secular trends and events can make this difficult to quantify. No consistent relationship was observed between campaign effectiveness and age, education, ethnicity or gender.


Subject(s)
Health Promotion/methods , Mass Media , Smoking Cessation/methods , Smoking Prevention , Adult , Health Behavior , Humans
17.
Cochrane Database Syst Rev ; (5): CD009329, 2013 May 31.
Article in English | MEDLINE | ID: mdl-23728690

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.


Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Benzazepines/therapeutic use , Bupropion/therapeutic use , Nicotinic Agonists/therapeutic use , Quinoxalines/therapeutic use , Smoking Cessation/methods , Tobacco Use Cessation Devices , Adult , Alkaloids/therapeutic use , Azocines/therapeutic use , Humans , Nortriptyline/therapeutic use , Quinolizines/therapeutic use , Randomized Controlled Trials as Topic , Review Literature as Topic , Smoking/drug therapy , Varenicline
18.
Cochrane Database Syst Rev ; 11: CD000146, 2012 Nov 14.
Article in English | MEDLINE | ID: mdl-23152200

ABSTRACT

BACKGROUND: The aim of nicotine replacement therapy (NRT) is 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. OBJECTIVES: The aims of this review were: To determine the effect of NRT compared to placebo in aiding smoking cessation, and to consider whether there is a difference in effect for the different forms of NRT (chewing gum, transdermal patches, oral and nasal sprays, inhalers and tablets/lozenges) in achieving abstinence from cigarettes. To determine whether the effect is influenced by the dosage, form and timing of use of NRT; the intensity of additional advice and support offered to the smoker; or the clinical setting in which the smoker is recruited and treated. To determine whether combinations of NRT are more likely to lead to successful quitting than one type alone. To determine whether NRT is more or less likely to lead to successful quitting compared to other pharmacotherapies. SEARCH METHODS: We 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 July 2012. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or to no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of participants, the dose, duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow-up. 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 RESULTS: We identified 150 trials; 117 with over 50,000 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The risk ratio (RR) of abstinence for any form of NRT relative to control was 1.60 (95% confidence interval [CI] 1.53 to 1.68). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 55 trials) for nicotine gum; 1.64 (95% CI 1.52 to 1.78, 43 trials) for nicotine patch; 1.95 (95% CI 1.61 to 2.36, 6 trials) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials) for nicotine inhaler; and 2.02 (95% CI 1.49 to 2.73, 4 trials) for nicotine nasal spray. One trial of oral spray had an RR of 2.48 (95% CI 1.24 to 4.94). The effects were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. The effect was similar in a small group of studies that aimed to assess use of NRT obtained without a prescription. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2 mg gum, but weaker evidence of a benefit from higher doses of patch. There was evidence that combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT (RR 1.34, 95% CI 1.18 to 1.51, 9 trials). The RR for NRT used for a short period prior to the quit date was 1.18 (95% CI 0.98 to 1.40, 8 trials), just missing statistical significance, though the efficacy increased when we pooled only patch trials and when we removed one trial in which confounding was likely. Five studies directly compared NRT to a non-nicotine pharmacotherapy, bupropion; there was no evidence of a difference in efficacy (RR 1.01; 95% CI 0.87 to 1.18). A combination of NRT and bupropion was more effective than bupropion alone (RR 1.24; 95% CI 1.06 to 1.45, 4 trials). Adverse effects from using NRT are related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. There is no evidence that NRT increases the risk of heart attacks. AUTHORS' CONCLUSIONS: All of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler 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 70%, regardless of setting. The 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.


Subject(s)
Smoking Cessation/methods , Tobacco Use Cessation Devices , Administration, Cutaneous , Administration, Inhalation , Chewing Gum , Humans , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Randomized Controlled Trials as Topic , Smoking Prevention , Tablets
19.
Cochrane Database Syst Rev ; (8): CD007072, 2012 Aug 15.
Article in English | MEDLINE | ID: mdl-22895958

ABSTRACT

BACKGROUND: By reducing the amount of nicotine that reaches the brain when a person smokes a cigarette, nicotine vaccines may help people to stop smoking or to prevent recent quitters from relapsing. OBJECTIVES: The aims of this review are to assess the efficacy of nicotine vaccines for smoking cessation and for relapse prevention, and to assess the frequency and type of adverse events associated with the use of nicotine vaccines. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Review Group specialised register for trials, using the term 'vaccine' in the title or abstract, or in a keyword (date of most recent search April 2012). To identify any other material including reviews and papers potentially relevant to the background or discussion sections, we also searched MEDLINE, EMBASE, and PsycINFO, combining terms for nicotine vaccines with terms for smoking and tobacco use, without design limits or limits for human subjects. We searched the Annual Meeting abstracts of the Society for Research on Nicotine and Tobacco up to 2012, using the search string 'vaccin'. We searched Google Scholar for 'nicotine vaccine'. We also searched company websites and Google for information related to specific vaccines. We searched clinicaltrials.gov in March 2012 for 'nicotine vaccine' and for the trade names of known vaccine candidates. SELECTION CRITERIA: We included randomized controlled trials of nicotine vaccines, at Phase II and Phase III trial stage and beyond, in adult smokers or recent ex-smokers. We included studies of nicotine vaccines used as part of smoking cessation or relapse prevention interventions. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, blinding of participants and personnel, reporting of outcomes, and completeness of follow-up.Our primary outcome measure was a minimum of six months abstinence from smoking. We used the most rigorous definition of abstinence, and preferred cessation rates at 12 months and biochemically validated rates where available. We have used the risk ratio (RR) to summarize individual trial outcomes. We have not pooled the current group of included studies as they cover different vaccines and variable regimens. MAIN RESULTS: There are no nicotine vaccines currently licensed for public use, but there are a number in development. We found four trials which met our inclusion criteria, three comparing NicVAX to placebo and one comparing NIC002 (formerly NicQbeta) to placebo. All were smoking cessation trials conducted by pharmaceutical companies as part of the drug development process, and all trials were judged to be at high or unclear risk of bias in at least one domain. Overall, 2642 smokers participated in the included studies in this review. None of the four included studies detected a statistically significant difference in long-term cessation between participants receiving vaccine and those receiving placebo. The RR for 12 month cessation in active and placebo groups was 1.35 (95% Confidence Interval (CI) 0.82 to 2.22) in the trial of NIC002 and 1.74 (95% CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which full results were not available, reported similar quit rates of approximately 11% in both groups. In the two studies with full results available, post hoc analyses detected higher cessation rates in participants with higher levels of nicotine antibodies, but these findings are not readily generalisable. The two studies with full results showed nicotine vaccines to be well tolerated, with the majority of adverse events classified as mild or moderate. In the study of NIC002, participants receiving the vaccine were more likely to report mild to moderate adverse events, most commonly flu-like symptoms, whereas in the study of NicVAX there was no significant difference between the two arms. Information on adverse events was not available for the large Phase III trials of NicVAX.Vaccine candidates are likely to undergo significant changes before becoming available to the general public, and those included in this review may not be the first to reach market; this limits the external validity of the results reported in this review in terms of both effectiveness and tolerability. AUTHORS' CONCLUSIONS: There is currently no evidence that nicotine vaccines enhance long-term smoking cessation. Rates of serious adverse events recorded in the two trials with full data available were low, and the majority of adverse events reported were at mild to moderate levels. The evidence available suggests nicotine vaccines do not induce compensatory smoking or affect withdrawal symptoms. No nicotine vaccines are currently licensed for use in any country but a number are under development.Further trials of nicotine vaccines are needed, comparing vaccines with placebo for smoking cessation. Further trials are also needed to explore the potential of nicotine vaccines to prevent relapse. Results from past, current and future research should be reported in full. Adverse events and serious adverse events should continue to be carefully monitored and thoroughly reported.


Subject(s)
Smoking Cessation/methods , Smoking/immunology , Vaccines/therapeutic use , Humans , Randomized Controlled Trials as Topic , Secondary Prevention , Smoking Prevention , Vaccines/adverse effects
20.
Cochrane Database Syst Rev ; (4): CD006103, 2012 Apr 18.
Article in English | MEDLINE | ID: mdl-22513936

ABSTRACT

BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in December 2011. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two recent cytisine trials (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled RR of 3.98 (95% confidence interval (CI) 2.01 to 7.87). One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). Fifteen trials compared varenicline with placebo for smoking cessation; three of these also included a bupropion treatment arm. We also found one open-label trial comparing varenicline plus counselling with counselling alone. We found one relapse prevention trial, comparing varenicline with placebo, and two open-label trials comparing varenicline with nicotine replacement therapy (NRT). We also include one trial in which all the participants were given varenicline, but received behavioural support either online or by phone calls, or by both methods. This trial is not included in the analyses, but contributes to the data on safety and tolerability. The included studies covered 12,223 participants, 8100 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.27 (95% CI 2.02 to 2.55; 14 trials, 6166 people, excluding one trial evaluating long term safety). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.09 (95% CI 1.56 to 2.78; 4 trials, 1272 people). The pooled RR for varenicline versus bupropion at one year was 1.52 (95% CI 1.22 to 1.88; 3 trials, 1622 people). The RR for varenicline versus NRT for point prevalence abstinence at 24 weeks was 1.13 (95% CI 0.94 to 1.35; 2 trials, 778 people). The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. A meta-analysis of reported serious adverse events occurring during or after active treatment and not necessarily considered attributable to treatment suggests there may be a one-third increase in the chance of severe adverse effects among people using varenicline (RR 1.36; 95% CI 1.04 to 1.79; 17 trials, 7725 people), but this finding needs to be tested further. Post-marketing safety data have raised questions about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation. The labelling of varenicline was amended in 2008, and the manufacturers produced a Medication Guide. Thus far, surveillance reports and secondary analyses of trial data are inconclusive, but the possibility of a link between varenicline and serious psychiatric or cardiovascular events cannot be ruled out. AUTHORS' CONCLUSIONS: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out.Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.


Subject(s)
Alkaloids/therapeutic use , Azepines/therapeutic use , Benzazepines/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Nicotinic Agonists/therapeutic use , Quinoxalines/therapeutic use , Smoking Cessation/methods , Azocines/therapeutic use , Bupropion/therapeutic use , Counseling/methods , Humans , Nicotine/adverse effects , Nicotine/antagonists & inhibitors , Nicotinic Agonists/adverse effects , Quinolizines/therapeutic use , Randomized Controlled Trials as Topic , Smoking/drug therapy , Substance Withdrawal Syndrome/prevention & control , Varenicline
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