Background
Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e‐liquid. People who smoke report using ECs to stop or reduce smoking, but ...some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014.
Objectives
To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long‐term smoking abstinence.
Search methods
We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference‐checking and contact with study authors.
Selection criteria
We included randomized controlled trials (RCTs) and randomized cross‐over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer.
Data collection and analysis
We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow‐up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed‐effect Mantel‐Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta‐analyses.
Main results
We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty‐five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non‐randomized studies), and the remainder at unclear risk.
There was moderate‐certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low‐certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants).
There was moderate‐certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non‐nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low‐certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants).
Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low‐certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non‐serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants).
Data from non‐randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit.
Authors' conclusions
There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow‐up was two years and the overall number of studies was small.
The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up‐to‐date information for decision‐makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
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.
Motivational Interviewing (MI) is a directive patient-centred style of counselling, designed to help people to explore and resolve ambivalence about behaviour change. It was developed as a treatment ...for alcohol abuse, but may help people to a make a successful attempt to quit smoking.
To determine whether or not motivational interviewing (MI) promotes smoking cessation.
We searched the Cochrane Tobacco Addiction Group Specialized Register for studies using the term motivat* NEAR2 (interview* OR enhanc* OR session* OR counsel* OR practi* OR behav*) in the title or abstract, or motivation* as a keyword. Date of the most recent search: August 2014.
Randomized controlled trials in which motivational interviewing or its variants were offered to tobacco users to assist cessation.
We extracted data in duplicate. The main outcome measure was abstinence from smoking after at least six months follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. We counted participants lost to follow-up as continuing smoking or relapsed. We performed meta-analysis using a fixed-effect Mantel-Haenszel model.
We identified 28 studies published between 1997 and 2014, involving over 16,000 participants. MI was conducted in one to six sessions, with the duration of each session ranging from 10 to 60 minutes. Interventions were delivered by primary care physicians, hospital clinicians, nurses or counsellors. Our meta-analysis of MI versus brief advice or usual care yielded a modest but significant increase in quitting (risk ratio (RR) 1.26; 95% confidence interval (CI) 1.16 to 1.36; 28 studies; N = 16,803). Subgroup analyses found that MI delivered by primary care physicians resulted in an RR of 3.49 (95% CI 1.53 to 7.94; 2 trials; N = 736). When delivered by counsellors the RR was smaller (1.25; 95% CI 1.15 to 1.63; 22 trials; N = 13,593) but MI still resulted in higher quit rates than brief advice or usual care. When we compared MI interventions conducted through shorter sessions (less than 20 minutes per session) to controls, this resulted in an RR of 1.69 (95% CI 1.34 to 2.12; 9 trials; N = 3651). Single-session treatments might increase the likelihood of quitting over multiple sessions, but both regimens produced positive outcomes. Evidence is unclear at present on the optimal number of follow-up calls.There was variation across the trials in treatment fidelity. All trials used some variant of motivational interviewing. Critical details in how it was modified for the particular study population, the training of therapists and the content of the counselling were sometimes lacking from trial reports.
Motivational interviewing may assist people to quit smoking. However, the results should be interpreted with caution, due to variations in study quality, treatment fidelity, between-study heterogeneity and the possibility of publication or selective reporting bias.
Abstract
Background
Smoking is a risk factor for most respiratory infections, but it may protect against SARS-CoV-2 infection. The objective was to assess whether smoking and e-cigarette use were ...associated with severe COVID-19.
Methods
This cohort ran from 24 January 2020 until 30 April 2020 at the height of the first wave of the SARS-CoV-2 epidemic in England. It comprised 7 869 534 people representative of the population of England with smoking status, demographic factors and diseases recorded by general practitioners in the medical records, which were linked to hospital and death data. The outcomes were COVID-19-associated hospitalization, intensive care unit (ICU) admission and death. The associations between smoking and the outcomes were assessed with Cox proportional hazards models, with sequential adjustment for confounding variables and indirect causal factors (body mass index and smoking-related disease).
Results
Compared with never smokers, people currently smoking were at lower risk of COVID-19 hospitalization, adjusted hazard ratios (HRs) were 0.64 (95% confidence intervals 0.60 to 0.69) for <10 cigarettes/day, 0.49 (0.41 to 0.59) for 10–19 cigarettes/day, and 0.61 (0.49 to 0.74) for ≥20 cigarettes/day. For ICU admission, the corresponding HRs were 0.31 (0.24 to 0.40), 0.15 (0.06 to 0.36), and 0.35 (0.17 to 0.74) and death were: 0.79 (0.70 to 0.89), 0.66 (0.48 to 0.90), and 0.77 (0.54 to 1.09) respectively. Former smokers were at higher risk of severe COVID-19: HRs: 1.07 (1.03 to 1.11) for hospitalization, 1.17 (1.04 to 1.31) for ICU admission, and 1.17 (1.10 to 1.24) for death. All-cause mortality was higher for current smoking than never smoking, HR 1.42 (1.36 to 1.48). Among e-cigarette users, the adjusted HR for e-cigarette use and hospitalization with COVID-19 was 1.06 (0.88 to 1.28), for ICU admission was 1.04 (0.57 to 1.89, and for death was 1.12 (0.81 to 1.55).
Conclusions
Current smoking was associated with a reduced risk of severe COVID-19 but the association with e-cigarette use was unclear. All-cause mortality remained higher despite this possible reduction in death from COVID-19 during an epidemic of SARS-CoV-2. Findings support investigating possible protective mechanisms of smoking for SARS-CoV-2 infection, including the ongoing trials of nicotine to treat COVID-19.
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 , 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.
...the use of self-reported abstinence in some trials is unlikely to have affected relative abstinence rates (e.g. risk ratios) and should be included in meta-analyses to maximize the use of existing ...research. ...they reported the use of very limited search terms (‘smoking cessation’ AND ‘abrupt’ OR ‘gradual’), which appear to have missed much of the relevant literature. ...we conclude that due to methodological limitations, the Tan et al.5 findings do not fully represent existing research.
Background
Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal ...may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
Objectives
To assess the evidence for the efficacy, safety and tolerability of medications with antidepressant properties in assisting long‐term tobacco smoking cessation in people who smoke cigarettes.
Search methods
We searched the Cochrane Tobacco Addiction Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting s, in May 2019.
Selection criteria
We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow‐up from efficacy analyses. We included trials with any follow‐up length in safety analyses.
Data collection and analysis
We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence.
The primary outcome measure was smoking cessation after at least six months follow‐up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). 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.
Similarly, we presented incidence of safety and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all‐cause mortality, and trial dropout due to drug, as RRs (95% CIs).
Main results
We included 115 studies (33 new to this update) in this review; most recruited adult participants from the community or from smoking cessation clinics. We judged 28 of the studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk did not change clinical interpretation of the results. There was high‐certainty evidence that bupropion increased long‐term smoking cessation rates (RR 1.64, 95% CI 1.52 to 1.77; I2 = 15%; 45 studies, 17,866 participants). There was insufficient evidence to establish whether participants taking bupropion were more likely to report SAEs compared to those taking placebo. Results were imprecise and CIs encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 21 studies, 10,625 participants; moderate‐certainty evidence, downgraded one level due to imprecision). We found high‐certainty evidence that use of bupropion resulted in more trial dropouts due to adverse events of the drug than placebo (RR 1.37, 95% CI 1.21 to 1.56; I2 = 19%; 25 studies, 12,340 participants). Participants randomized to bupropion were also more likely to report psychiatric AEs compared with those randomized to placebo (RR 1.25, 95% CI 1.15 to 1.37; I2 = 15%; 6 studies, 4439 participants).
We also looked at the safety and efficacy of bupropion when combined with other non‐antidepressant smoking cessation therapies. There was insufficient evidence to establish whether combination bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.19, 95% CI 0.94 to 1.51; I2 = 52%; 12 studies, 3487 participants), or whether combination bupropion and varenicline resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). We judged the certainty of evidence to be low and moderate, respectively; in both cases due to imprecision, and also due to inconsistency in the former. Safety data were sparse for these comparisons, making it difficult to draw clear conclusions.
A meta‐analysis of six studies provided evidence that bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.71, 95% CI 0.64 to 0.79; I2 = 0%; 6 studies, 6286 participants), whilst there was no evidence of a difference in efficacy between bupropion and NRT (RR 0.99, 95% CI 0.91 to 1.09; I2 = 18%; 10 studies, 8230 participants).
We also found some evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I2 = 16%; 6 studies, 975 participants), whilst there was insufficient evidence to determine whether bupropion or nortriptyline were more effective when compared with one another (RR 1.30 (favouring bupropion), 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
Authors' conclusions
There is high‐certainty evidence that bupropion can aid long‐term smoking cessation. However, bupropion also increases the number of adverse events, including psychiatric AEs, and there is high‐certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high‐certainty evidence, further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over front‐line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.
Rationale
Using nicotine replacement therapy (NRT) whilst smoking, prior to quitting, is called preloading. Two reviews have estimated the effect of preloading on abstinence, but need updating. ...Neither investigated possible mediators or moderators of the effect, which could have implications for individual treatment plans.
Objectives
To update the nicotine preloading efficacy estimate and test four hypotheses: (1) Efficacy is mediated through reduced smoking reward, (2) efficacy is mediated through increased NRT adherence post-quit, (3) efficacy is mediated through increased confidence, and (4) behavioural support modifies efficacy.
Methods
Randomised controlled trials were included that allocated cigarette smokers attempting to quit to either a preloading or control condition. A Mantel–Haenszel fixed-effect model was used to calculate risk ratios from quit rates at short- and long-term follow-ups. We carried out sub-group analyses and synthesised the data available on possible mediators and moderators qualitatively.
Results
Eight relevant studies were included, with 2,813 participants. The risk ratio (RR) for short-term abstinence was 1.05, 95% confidence intervals (CI) = 0.92, 1.19, and for long-term abstinence 1.16, 95% CI = 0.97, 1.38. There was a marginal benefit of using nicotine patch rather than gum for preloading, significant at short-term follow-up, and no significant benefit of more intensive pre-quit behavioural support.
Conclusions
We found a weak non-significant effect of nicotine preloading on abstinence. None of our mediational hypotheses received strong support, however evidence suggests that efficacy was enhanced by the patch over acute NRT. Future research needs to investigate the mechanisms of preloading by carrying out mediational analysis.
Background
Populations experiencing homelessness have high rates of tobacco use and experience substantial barriers to cessation. Tobacco‐caused conditions are among the leading causes of morbidity ...and mortality among people experiencing homelessness, highlighting an urgent need for interventions to reduce the burden of tobacco use in this population.
Objectives
To assess whether interventions designed to improve access to tobacco cessation interventions for adults experiencing homelessness lead to increased numbers engaging in or receiving treatment, and whether interventions designed to help adults experiencing homelessness to quit tobacco lead to increased tobacco abstinence. To also assess whether tobacco cessation interventions for adults experiencing homelessness affect substance use and mental health.
Search methods
We searched the Cochrane Tobacco Addiction Group Specialized Register, MEDLINE, Embase and PsycINFO for studies using the terms: un‐housed*, homeless*, housing instability, smoking cessation, tobacco use disorder, smokeless tobacco. We also searched trial registries to identify unpublished studies. Date of the most recent search: 06 January 2020.
Selection criteria
We included randomized controlled trials that recruited people experiencing homelessness who used tobacco, and investigated interventions focused on the following: 1) improving access to relevant support services; 2) increasing motivation to quit tobacco use; 3) helping people to achieve abstinence, including but not limited to behavioral support, tobacco cessation pharmacotherapies, contingency management, and text‐ or app‐based interventions; or 4) encouraging transitions to long‐term nicotine use that did not involve tobacco. Eligible comparators included no intervention, usual care (as defined by the studies), or another form of active intervention.
Data collection and analysis
We followed standard Cochrane methods. Tobacco cessation was measured at the longest time point for each study, on an intention‐to‐treat basis, using the most rigorous definition available. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study where possible. We grouped eligible studies according to the type of comparison (contingent reinforcement in addition to usual smoking cessation care; more versus less intensive smoking cessation interventions; and multi‐issue support versus smoking cessation support only), and carried out meta‐analyses where appropriate, using a Mantel‐Haenszel random‐effects model. We also extracted data on quit attempts, effects on mental and substance‐use severity, and meta‐analyzed these outcomes where sufficient data were available.
Main results
We identified 10 studies involving 1634 participants who smoked combustible tobacco at enrolment. One of the studies was ongoing. Most of the trials included participants who were recruited from community‐based sites such as shelters, and three included participants who were recruited from clinics. We judged three studies to be at high risk of bias in one or more domains. We identified low‐certainty evidence, limited by imprecision, that contingent reinforcement (rewards for successful smoking cessation) plus usual smoking cessation care was not more effective than usual care alone in promoting abstinence (RR 0.67, 95% CI 0.16 to 2.77; 1 trial, 70 participants). We identified very low‐certainty evidence, limited by risk of bias and imprecision, that more intensive behavioral smoking cessation support was more effective than brief intervention in promoting abstinence at six‐month follow‐up (RR 1.64, 95% CI 1.01 to 2.69; 3 trials, 657 participants; I2 = 0%). There was low‐certainty evidence, limited by bias and imprecision, that multi‐issue support (cessation support that also encompassed help to deal with other challenges or addictions) was not superior to targeted smoking cessation support in promoting abstinence (RR 0.95, 95% CI 0.35 to 2.61; 2 trials, 146 participants; I2 = 25%). More data on these types of interventions are likely to change our interpretation of these data. Single studies that examined the effects of text‐messaging support, e‐cigarettes, or cognitive behavioral therapy for smoking cessation provided inconclusive results. Data on secondary outcomes, including mental health and substance use severity, were too sparse to draw any meaningful conclusions on whether there were clinically‐relevant differences. We did not identify any studies that explicitly assessed interventions to increase access to tobacco cessation care; we were therefore unable to assess our secondary outcome ‘number of participants receiving treatment'.
Authors' conclusions
There is insufficient evidence to assess the effects of any tobacco cessation interventions specifically in people experiencing homelessness. Although there was some evidence to suggest a modest benefit of more intensive behavioral smoking cessation interventions when compared to less intensive interventions, our certainty in this evidence was very low, meaning that further research could either strengthen or weaken this effect. There is insufficient evidence to assess whether the provision of tobacco cessation support and its effects on quit attempts has any effect on the mental health or other substance‐use outcomes of people experiencing homelessness. Although there is no reason to believe that standard tobacco cessation treatments work any differently in people experiencing homelessness than in the general population, these findings highlight a need for high‐quality studies that address additional ways to engage and support people experiencing homelessness, in the context of the daily challenges they face. These studies should have adequate power and put effort into retaining participants for long‐term follow‐up of at least six months. Studies should also explore interventions that increase access to cessation services, and address the social and environmental influences of tobacco use among people experiencing homelessness. Finally, studies should explore the impact of tobacco cessation on mental health and substance‐use outcomes.
Background
Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e‐liquid. Some people who smoke use ECs to stop or reduce smoking, but some ...organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This is an update of a review first published in 2014.
Objectives
To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke achieve long‐term smoking abstinence.
Search methods
We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 February 2021, together with reference‐checking and contact with study authors.
Selection criteria
We included randomized controlled trials (RCTs) and randomized cross‐over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer.
Data collection and analysis
We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow‐up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed‐effect Mantel‐Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta‐analyses.
Main results
We included 56 completed studies, representing 12,804 participants, of which 29 were RCTs. Six of the 56 included studies were new to this review update. Of the included studies, we rated five (all contributing to our main comparisons) at low risk of bias overall, 41 at high risk overall (including the 25 non‐randomized studies), and the remainder at unclear risk.
There was moderate‐certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low‐certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants).
There was moderate‐certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non‐nicotine EC (RR 1.70, 95% CI 1.03 to 2.81; I2 = 0%; 4 studies, 1057 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 11). These trials mainly used older EC with relatively low nicotine delivery. There was moderate‐certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.60, 95% CI 0.15 to 2.44; I2 = n/a; 4 studies, 494 participants).
Compared to behavioral support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.70, 95% CI 1.39 to 5.26; I2 = 0%; 5 studies, 2561 participants). In absolute terms this represents an increase of seven per 100 (95% CI 2 to 17). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs differed, but some evidence that non‐serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants; SAEs: RR 1.17, 95% CI 0.33 to 4.09; I2 = 5%; 6 studies, 1011 participants, very low certainty).
Data from non‐randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit.
Authors' conclusions
There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the size of effect, particularly when using modern EC products. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, though evidence indicated no difference in AEs between nicotine and non‐nicotine ECs. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow‐up was two years and the overall number of studies was small.
The evidence is limited mainly by imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up‐to‐date information, this review is now a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
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