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American Journal of Preventive Medicine Aug 2018To provide a systematic review and cost-effectiveness analysis on smoking interventions targeting smokers not ready to quit, a population that makes up approximately 32%... (Meta-Analysis)
Meta-Analysis
CONTEXT
To provide a systematic review and cost-effectiveness analysis on smoking interventions targeting smokers not ready to quit, a population that makes up approximately 32% of current smokers.
EVIDENCE ACQUISITION
Twenty-two studies on pharmacological, behavioral, and combination smoking-cessation interventions targeting smokers not ready to quit (defined as those who reported they were not ready to quit at the time of the study) published between 2000 and 2017 were analyzed. The effectiveness (measured by the number needed to treat) and cost effectiveness (measured by costs per quit) of interventions were calculated. All data collection and analyses were performed in 2017.
EVIDENCE SYNTHESIS
Smoking interventions targeting smokers not ready to quit can be as effective as similar interventions for smokers ready to quit; however, costs of intervening on this group may be higher for some intervention types. The most cost-effective interventions identified for this group were those using varenicline and those using behavioral interventions.
CONCLUSIONS
Updating clinical recommendations to provide cessation interventions for this group is recommended. Further research on development of cost-effective treatments and effective strategies for recruitment and outreach for this group are needed. Additional studies may allow for more nuanced comparisons of treatment types among this group.
Topics: Cost-Benefit Analysis; Health Behavior; Smokers; Smoking; Smoking Cessation; Smoking Cessation Agents; United States; Varenicline
PubMed: 29903568
DOI: 10.1016/j.amepre.2018.04.021 -
The Cochrane Database of Systematic... Sep 2017Tobacco smoking is the leading preventable cause of death worldwide, which makes it essential to stimulate smoking cessation. The financial cost of smoking cessation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tobacco smoking is the leading preventable cause of death worldwide, which makes it essential to stimulate smoking cessation. The financial cost of smoking cessation treatment can act as a barrier to those seeking support. We hypothesised that provision of financial assistance for people trying to quit smoking, or reimbursement of their care providers, could lead to an increased rate of successful quit attempts. This is an update of the original 2005 review.
OBJECTIVES
The primary objective of this review was to assess the impact of reducing the costs for tobacco smokers or healthcare providers for using or providing smoking cessation treatment through healthcare financing interventions on abstinence from smoking. The secondary objectives were to examine the effects of different levels of financial support on the use or prescription of smoking cessation treatment, or both, and on the number of smokers making a quit attempt (quitting smoking for at least 24 hours). We also assessed the cost effectiveness of different financial interventions, and analysed the costs per additional quitter, or per quality-adjusted life year (QALY) gained.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register in September 2016.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs), controlled trials and interrupted time series studies involving financial benefit interventions to smokers or their healthcare providers, or both.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed the quality of the included studies. We calculated risk ratios (RR) for individual studies on an intention-to-treat basis and performed meta-analysis using a random-effects model.
MAIN RESULTS
In the current update, we have added six new relevant studies, resulting in a total of 17 studies included in this review involving financial interventions directed at smokers or healthcare providers, or both.Full financial interventions directed at smokers had a favourable effect on abstinence at six months or longer when compared to no intervention (RR 1.77, 95% CI 1.37 to 2.28, I² = 33%, 9333 participants). There was no evidence that full coverage interventions increased smoking abstinence compared to partial coverage interventions (RR 1.02, 95% CI 0.71 to 1.48, I² = 64%, 5914 participants), but partial coverage interventions were more effective in increasing abstinence than no intervention (RR 1.27 95% CI 1.02 to 1.59, I² = 21%, 7108 participants). The economic evaluation showed costs per additional quitter ranging from USD 97 to USD 7646 for the comparison of full coverage with partial or no coverage.There was no clear evidence of an effect on smoking cessation when we pooled two trials of financial incentives directed at healthcare providers (RR 1.16, CI 0.98 to 1.37, I² = 0%, 2311 participants).Full financial interventions increased the number of participants making a quit attempt when compared to no interventions (RR 1.11, 95% CI 1.04 to 1.17, I² = 15%, 9065 participants). There was insufficient evidence to show whether partial financial interventions increased quit attempts compared to no interventions (RR 1.13, 95% CI 0.98 to 1.31, I² = 88%, 6944 participants).Full financial interventions increased the use of smoking cessation treatment compared to no interventions with regard to various pharmacological and behavioural treatments: nicotine replacement therapy (NRT): RR 1.79, 95% CI 1.54 to 2.09, I² = 35%, 9455 participants; bupropion: RR 3.22, 95% CI 1.41 to 7.34, I² = 71%, 6321 participants; behavioural therapy: RR 1.77, 95% CI 1.19 to 2.65, I² = 75%, 9215 participants.There was evidence that partial coverage compared to no coverage reported a small positive effect on the use of bupropion (RR 1.15, 95% CI 1.03 to 1.29, I² = 0%, 6765 participants). Interventions directed at healthcare providers increased the use of behavioural therapy (RR 1.69, 95% CI 1.01 to 2.86, I² = 85%, 25820 participants), but not the use of NRT and/or bupropion (RR 0.94, 95% CI 0.76 to 1.18, I² = 6%, 2311 participants).We assessed the quality of the evidence for the main outcome, abstinence from smoking, as moderate. In most studies participants were not blinded to the different study arms and researchers were not blinded to the allocated interventions. Furthermore, there was not always sufficient information on attrition rates. We detected some imprecision but we judged this to be of minor consequence on the outcomes of this study.
AUTHORS' CONCLUSIONS
Full financial interventions directed at smokers when compared to no financial interventions increase the proportion of smokers who attempt to quit, use smoking cessation treatments, and succeed in quitting. There was no clear and consistent evidence of an effect on smoking cessation from financial incentives directed at healthcare providers. We are only moderately confident in the effect estimate because there was some risk of bias due to a lack of blinding in participants and researchers, and insufficient information on attrition rates.
Topics: Cost-Benefit Analysis; Financing, Government; Healthcare Financing; Humans; Insurance Coverage; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation; Tobacco Use Disorder
PubMed: 28898403
DOI: 10.1002/14651858.CD004305.pub5 -
BMC Psychiatry Jul 2017People with severe mental ill health are more likely to smoke than those in the general population. It is therefore important that effective smoking cessation strategies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with severe mental ill health are more likely to smoke than those in the general population. It is therefore important that effective smoking cessation strategies are used to help people with severe mental ill health to stop smoking. This study aims to assess the effectiveness and cost -effectiveness of smoking cessation and reduction strategies in adults with severe mental ill health in both inpatient and outpatient settings.
METHODS
This is an update of a previous systematic review. Electronic databases were searched during September 2016 for randomised controlled trials comparing smoking cessation interventions to each other, usual care, or placebo. Data was extracted on biochemically-verified, self-reported smoking cessation (primary outcome), as well as on smoking reduction, body weight, psychiatric symptom, and adverse events (secondary outcomes).
RESULTS
We included 26 trials of pharmacological and/or behavioural interventions. Eight trials comparing bupropion to placebo were pooled showing that bupropion improved quit rates significantly in the medium and long term but not the short term (short term RR = 6.42 95% CI 0.82-50.07; medium term RR = 2.93 95% CI 1.61-5.34; long term RR = 3.04 95% CI 1.10-8.42). Five trials comparing varenicline to placebo showed that that the addition of varenicline improved quit rates significantly in the medium term (RR = 4.13 95% CI 1.36-12.53). The results from five trials of specialised smoking cessation programmes were pooled and showed no evidence of benefit in the medium (RR = 1.32 95% CI 0.85-2.06) or long term (RR = 1.33 95% CI 0.85-2.08). There was insufficient data to allowing pooling for all time points for varenicline and trials of specialist smoking cessation programmes. Trials suggest few adverse events although safety data were not always reported. Only one pilot study reported cost effectiveness data.
CONCLUSIONS
Bupropion and varenicline, which have been shown to be effective in the general population, also work for people with severe mental ill health and their use in patients with stable psychiatric conditions. Despite good evidence for the effectiveness of smoking cessation interventions for people with severe mental ill health, the percentage of people with severe mental ill health who smoke remains higher than that for the general population.
Topics: Antidepressive Agents, Second-Generation; Bupropion; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Mental Disorders; Nicotinic Agonists; Smoking; Smoking Cessation; Varenicline
PubMed: 28705244
DOI: 10.1186/s12888-017-1419-7 -
The Cochrane Database of Systematic... Oct 2016Although 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Biomarkers; Bupropion; Carbon Monoxide; Cotinine; Electronic Nicotine Delivery Systems; Humans; Nicotine; Nicotinic Agonists; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Smoking Prevention; Tobacco Use Cessation Devices; Tobacco Use Disorder
PubMed: 27734465
DOI: 10.1002/14651858.CD005231.pub3 -
The Cochrane Database of Systematic... Aug 2016Smoking cessation is the most important treatment for smokers with chronic obstructive pulmonary disease (COPD), but little is known about the effectiveness of different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Smoking cessation is the most important treatment for smokers with chronic obstructive pulmonary disease (COPD), but little is known about the effectiveness of different smoking cessation interventions for this particular group of smokers.
OBJECTIVES
To evaluate the effectiveness of behavioural or pharmacological smoking cessation interventions, or both, in smokers with COPD.
SEARCH METHODS
We searched all records in the Cochrane Airways Group Specialised Register of Trials. In addition to this electronic search, we searched clinical trial registries for planned, ongoing, and unpublished trials. We searched all databases from their inception. We checked the reference lists of all included studies and of other systematic reviews in relevant topic areas. We searched for errata or retractions from eligible trials on PubMed. We conducted our most recent search in March 2016.
SELECTION CRITERIA
We included randomised controlled trials assessing the effectiveness of any behavioural or pharmacological treatment, or both, in smokers with COPD reporting at least six months of follow-up abstinence rates.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and performed the methodological quality assessment for each study. We resolved any disagreements by consensus.
MAIN RESULTS
We included 16 studies (involving 13,123 participants) in this systematic review, two of which were of high quality. These two studies showed that nicotine sublingual tablet and varenicline increased the quit rate over placebo (risk ratio (RR) 2.60 (95% confidence interval (CI) 1.29 to 5.24) and RR 3.34 (95% CI 1.88 to 5.92)). Pooled results of two studies also showed a positive effect of bupropion compared with placebo (RR 2.03 (95% CI 1.26 to 3.28)). When pooling these four studies, we found high-quality evidence for the effectiveness of pharmacotherapy plus high-intensity behavioural treatment compared with placebo plus high-intensity behavioural treatment (RR 2.53 (95% CI 1.83 to 3.50)). Furthermore, we found some evidence that high-intensity behavioural treatment increased abstinence rates when compared with usual care (RR 25.38 (95% CI 8.03 to 80.22)) or low-intensity behavioural treatment (RR 2.18 (95% CI 1.05 to 4.49)). Finally, the results showed effectiveness of various combinations of psychosocial and pharmacological interventions.
AUTHORS' CONCLUSIONS
We found high-quality evidence in a meta-analysis including four (1,540 participants) of the 16 included studies that a combination of behavioural treatment and pharmacotherapy is effective in helping smokers with COPD to quit smoking. Furthermore, we conclude that there is no convincing evidence for preferring any particular form of behavioural or pharmacological treatment.
Topics: Adult; Behavior Therapy; Bupropion; Combined Modality Therapy; Female; Humans; Male; Nicotine; Nicotinic Agonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Smoking Cessation; Varenicline
PubMed: 27545342
DOI: 10.1002/14651858.CD010744.pub2 -
The Cochrane Database of Systematic... Jun 2016Tobacco use is highly prevalent amongst people living with HIV/AIDS (PLWHA) and has a substantial impact on morbidity and mortality. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tobacco use is highly prevalent amongst people living with HIV/AIDS (PLWHA) and has a substantial impact on morbidity and mortality.
OBJECTIVES
To assess the effectiveness of interventions to motivate and assist tobacco use cessation for people living with HIV/AIDS (PLWHA), and to evaluate the risks of any harms associated with those interventions.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO in June 2015. We also searched EThOS, ProQuest, four clinical trial registries, reference lists of articles, and searched for conference abstracts using Web of Science and handsearched speciality conference databases.
SELECTION CRITERIA
Controlled trials of behavioural or pharmacological interventions for tobacco cessation for PLWHA.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted all data using a standardised electronic data collection form. They extracted data on the nature of the intervention, participants, and proportion achieving abstinence and they contacted study authors to obtain missing information. We collected data on long-term (greater than or equal to six months) and short-term (less than six months) outcomes. Where appropriate, we performed meta-analysis and estimated the pooled effects using the Mantel-Haenszel fixed-effect method. Two authors independently assessed and reported the risk of bias according to prespecified criteria.
MAIN RESULTS
We identified 14 studies relevant to this review, of which we included 12 in a meta-analysis (n = 2087). All studies provided an intervention combining behavioural support and pharmacotherapy, and in most studies this was compared to a less intensive control, typically comprising a brief behavioural intervention plus pharmacotherapy.There was moderate quality evidence from six studies for the long-term abstinence outcome, which showed no evidence of effect for more intense cessation interventions: (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.72 to 1.39) with no evidence of heterogeneity (I(2) = 0%). The pooled long-term abstinence was 8% in both intervention and control conditions. There was very low quality evidence from 11 studies that more intense tobacco cessation interventions were effective in achieving short-term abstinence (RR 1.51, 95% CI 1.15 to 2.00); there was moderate heterogeneity (I(2) = 42%). Abstinence in the control group at short-term follow-up was 8% (n = 67/848) and in the intervention group was 13% (n = 118/937). The effect of tailoring the intervention for PLWHA was unclear. We further investigated the effect of intensity of behavioural intervention via number of sessions and total duration of contact. We failed to detect evidence of a difference in effect according to either measure of intensity, although there were few studies in each subgroup. It was not possible to perform the planned analysis of adverse events or HIV outcomes since these were not reported in more than one study.
AUTHORS' CONCLUSIONS
There is moderate quality evidence that combined tobacco cessation interventions provide similar outcomes to controls in PLWHA in the long-term. There is very low quality evidence that combined tobacco cessation interventions were effective in helping PLWHA achieve short-term abstinence. Despite this, tobacco cessation interventions should be offered to PLWHA, since even non-sustained periods of abstinence have proven benefits. Further large, well designed studies of cessation interventions for PLWHA are needed.
Topics: Acquired Immunodeficiency Syndrome; Behavior Therapy; HIV Infections; Humans; Nicotinic Agonists; Randomized Controlled Trials as Topic; Smoking Cessation; Time Factors; Tobacco Use Cessation; Varenicline
PubMed: 27292836
DOI: 10.1002/14651858.CD011120.pub2 -
The Cochrane Database of Systematic... May 2016Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Alkaloids; Azepines; Azocines; Benzazepines; Bupropion; Counseling; Heterocyclic Compounds, 4 or More Rings; Humans; Nicotine; Nicotinic Agonists; Quinolizines; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Substance Withdrawal Syndrome; Varenicline
PubMed: 27158893
DOI: 10.1002/14651858.CD006103.pub7 -
Addiction (Abingdon, England) Sep 2016To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness. (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness.
DESIGN
A systematic review and meta-analysis of randomised controlled trials that compared varenicline with a placebo or an alternative intervention for smoking cessation or reduction.
SETTING
Both in- and out-patient settings in any country.
PARTICIPANTS
Adult patients aged 18 years and over with any type of severe mental illness. The systematic review included eight studies comprising 398 participants.
MEASURES
Primary outcome measures were (1) smoking cessation, (2) smoking reduction measured by changes in the number of cigarettes smoked per day and (3) number of psychiatric adverse events, which were collected at the end of treatment.
FINDINGS
The random-effect pooled estimates from the five studies that reported smoking-related outcomes found that varenicline is statistically superior to placebo in smoking cessation [risk ratios 4.33; 95% confidence interval (CI) = 1.96-9.56], and smoking reduction was higher in varenicline groups (mean reduced daily cigarettes was 6.39; 95% CI = 2.22-10.56). There is no significant difference regarding neuropsychiatric and other adverse events.
CONCLUSIONS
Varenicline appears to be significantly more effective than placebo in assisting with smoking cessation and reduction in people with severe mental illness. There appears to be no clear evidence that varenicline was associated with an increased risk of neuropsychiatric or other adverse events compared with placebo.
Topics: Comorbidity; Humans; Mental Disorders; Nicotinic Agonists; Smoking; Smoking Cessation; Tobacco Smoking; Varenicline
PubMed: 27043328
DOI: 10.1111/add.13415 -
The Cochrane Database of Systematic... Mar 2016Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are effective in helping people to stop smoking. Combining both treatment approaches is recommended where possible, but the size of the treatment effect with different combinations and in different settings and populations is unclear.
OBJECTIVES
To assess the effect of combining behavioural support and medication to aid smoking cessation, compared to a minimal intervention or usual care, and to identify whether there are different effects depending on characteristics of the treatment setting, intervention, population treated, or take-up of treatment.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2015 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials evaluating combinations of pharmacotherapy and behavioural support for smoking cessation, compared to a control receiving usual care or brief advice or less intensive behavioural 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
Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by two authors. Data was extracted by one author and checked by another.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
Fifty-three studies with a total of more than 25,000 participants met the inclusion criteria. A large proportion of studies recruited people in healthcare settings or with specific health needs. Most studies provided NRT. Behavioural support was typically provided by specialists in cessation counselling, who offered between four and eight contact sessions. The planned maximum duration of contact was typically more than 30 minutes but less than 300 minutes. Overall, studies were at low or unclear risk of bias, and findings were not sensitive to the exclusion of any of the six studies rated at high risk of bias in one domain. One large study (the Lung Health Study) contributed heterogeneity due to a substantially larger treatment effect than seen in other studies (RR 3.88, 95% CI 3.35 to 4.50). Since this study used a particularly intensive intervention which included extended availability of nicotine gum, multiple group sessions and long term maintenance and recycling contacts, the results may not be comparable with the interventions used in other studies, and hence it was not pooled in other analyses. Based on the remaining 52 studies (19,488 participants) there was high quality evidence (using GRADE) for a benefit of combined pharmacotherapy and behavioural treatment compared to usual care, brief advice or less intensive behavioural support (RR 1.83, 95% CI 1.68 to 1.98) with moderate statistical heterogeneity (I² = 36%).The pooled estimate for 43 trials that recruited participants in healthcare settings (RR 1.97, 95% CI 1.79 to 2.18) was higher than for eight trials with community-based recruitment (RR 1.53, 95% CI 1.33 to 1.76). Compared to the first version of the review, previous weak evidence of differences in other subgroup analyses has disappeared. We did not detect differences between subgroups defined by motivation to quit, treatment provider, number or duration of support sessions, or take-up of treatment.
AUTHORS' CONCLUSIONS
Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care. Updating this review with an additional 12 studies (5,000 participants) did not materially change the effect estimate. Although trials differed in the details of their populations and interventions, we did not detect any factors that modified treatment effects apart from the recruitment setting. We did not find evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects.
Topics: Adult; Behavior Therapy; Combined Modality Therapy; Counseling; Female; Humans; Male; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 27009521
DOI: 10.1002/14651858.CD008286.pub3 -
Journal of the American Heart... Feb 2016Varenicline is an efficacious smoking-cessation drug. However, previous meta-analyses provide conflicting results regarding its cardiovascular safety. The publication of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Varenicline is an efficacious smoking-cessation drug. However, previous meta-analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction.
METHODS AND RESULTS
We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all-cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian-Laird random-effects models. Thirty-eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72-1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57-1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64-1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all-cause mortality found no difference between groups (RR 0.88, 95% CI 0.50-1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40-3.83) and without (RR 0.77, 95% CI 0.40-1.48) cardiovascular disease.
CONCLUSIONS
We found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long-term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation.
Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Nicotinic Agonists; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Smoking Prevention; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline; Young Adult
PubMed: 26903004
DOI: 10.1161/JAHA.115.002849