BACKGROUND: The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES: To assess the evidence for the efficacy, harms, 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 Group Specialised Register, most recently on 29 April 2022.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms.
DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms 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 dropouts due to treatment. We carried out meta-analyses where appropriate.
MAIN RESULTS: We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found 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), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. 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 may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. 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 other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
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). This is an update of a Cochrane Review first published in 2007.
OBJECTIVES: To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO. SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs).
MAIN RESULTS: We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I2 = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I2 = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I2 = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I2 = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I2 = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I2 = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I2 = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I2 = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I2 = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I2 = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I2 = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I2 = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I2 = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I2 = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I2 = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I2 = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I2 not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I2 not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit.
AUTHORS' CONCLUSIONS: Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.
BACKGROUND: Dental professionals are well placed to help their patients stop using tobacco products. Large proportions of the population visit the dentist regularly. In addition, the adverse effects of tobacco use on oral health provide a context that dental professionals can use to motivate a quit attempt.
OBJECTIVES: To assess the effectiveness, adverse events and oral health effects of tobacco cessation interventions offered by dental professionals.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register up to February 2020.
SELECTION CRITERIA: We included randomised and quasi-randomised clinical trials assessing tobacco cessation interventions conducted by dental professionals in the dental practice or community setting, with at least six months of follow-up.
DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts for potential inclusion and extracted data from included trials. We resolved disagreements by consensus. The primary outcome was abstinence from all tobacco use (e.g. cigarettes, smokeless tobacco) at the longest follow-up, using the strictest definition of abstinence reported. Individual study effects and pooled effects were summarised as risk ratios (RR) and 95% confidence intervals (CI), using Mantel-Haenszel random-effects models to combine studies where appropriate. We assessed statistical heterogeneity with the I2 statistic. We summarised secondary outcomes narratively.
MAIN RESULTS: Twenty clinical trials involving 14,897 participants met the criteria for inclusion in this review. Sixteen studies assessed the effectiveness of interventions for tobacco-use cessation in dental clinics and four assessed this in community (school or college) settings. Five studies included only smokeless tobacco users, and the remaining studies included either smoked tobacco users only, or a combination of both smoked and smokeless tobacco users. All studies employed behavioural interventions, with four offering nicotine treatment (nicotine replacement therapy (NRT) or e-cigarettes) as part of the intervention. We judged three studies to be at low risk of bias, one to be at unclear risk of bias, and the remaining 16 studies to be at high risk of bias. Compared with usual care, brief advice, very brief advice, or less active treatment, we found very low-certainty evidence of benefit from behavioural support provided by dental professionals, comprising either one session (RR 1.86, 95% CI 1.01 to 3.41; I2 = 66%; four studies, n = 6328), or more than one session (RR 1.90, 95% CI 1.17 to 3.11; I2 = 61%; seven studies, n = 2639), on abstinence from tobacco use at least six months from baseline. We found moderate-certainty evidence of benefit from behavioural interventions provided by dental professionals combined with the provision of NRT or e-cigarettes, compared with no intervention, usual care, brief, or very brief advice only (RR 2.76, 95% CI 1.58 to 4.82; I2 = 0%; four studies, n = 1221). We did not detect a benefit from multiple-session behavioural support provided by dental professionals delivered in a high school or college, instead of a dental setting (RR 1.51, 95% CI 0.86 to 2.65; I2 = 83%; three studies, n = 1020; very low-certainty evidence). Only one study reported adverse events or oral health outcomes, making it difficult to draw any conclusions.
AUTHORS' CONCLUSIONS: There is very low-certainty evidence that quit rates increase when dental professionals offer behavioural support to promote tobacco cessation. There is moderate-certainty evidence that tobacco abstinence rates increase in cigarette smokers if dental professionals offer behavioural support combined with pharmacotherapy. Further evidence is required to be certain of the size of the benefit and whether adding pharmacological interventions is more effective than behavioural support alone. Future studies should use biochemical validation of abstinence so as to preclude the risk of detection bias. There is insufficient evidence on whether these interventions lead to adverse effects, but no reasons to suspect that these effects would be specific to interventions delivered by dental professionals. There was insufficient evidence that interventions affected oral health.
BACKGROUND: Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) are becoming widely used, but their efficacy and safety when used for smoking cessation in pregnancy are also unknown.
OBJECTIVES: To determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with either placebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs with additional intervention components not matched between trial arms.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trial treatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate.
MAIN RESULTS: We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities, or neonatal death. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group.
AUTHORS' CONCLUSIONS: NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.
BACKGROUND: Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines.
OBJECTIVES: To evaluate the effect of telephone support to help smokers quit, including proactive or reactive counselling, or the provision of other information to smokers calling a helpline.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, clinicaltrials.gov, and the ICTRP for studies of telephone counselling, using search terms including 'hotlines' or 'quitline' or 'helpline'. Date of the most recent search: May 2018.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials which offered proactive or reactive telephone counselling to smokers to assist smoking cessation.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We pooled studies using a random-effects model and assessed statistical heterogeneity amongst subgroups of clinically comparable studies using the I2 statistic. In trials including smokers who did not call a quitline, we used meta-regression to investigate moderation of the effect of telephone counselling by the planned number of calls in the intervention, trial selection of participants that were motivated to quit, and the baseline support provided together with telephone counselling (either self-help only, brief face-to-face intervention, pharmacotherapy, or financial incentives).
MAIN RESULTS: We identified 104 trials including 111,653 participants that met the inclusion criteria. Participants were mostly adult smokers from the general population, but some studies included teenagers, pregnant women, and people with long-term or mental health conditions. Most trials (58.7%) were at high risk of bias, while 30.8% were at unclear risk, and only 11.5% were at low risk of bias for all domains assessed. Most studies (100/104) assessed proactive telephone counselling, as opposed to reactive forms.Among trials including smokers who contacted helplines (32,484 participants), quit rates were higher for smokers receiving multiple sessions of proactive counselling (risk ratio (RR) 1.38, 95% confidence interval (CI) 1.19 to 1.61; 14 trials, 32,484 participants; I2 = 72%) compared with a control condition providing self-help materials or brief counselling in a single call. Due to the substantial unexplained heterogeneity between studies, we downgraded the certainty of the evidence to moderate.In studies that recruited smokers who did not call a helpline, the provision of telephone counselling increased quit rates (RR 1.25, 95% CI 1.15 to 1.35; 65 trials, 41,233 participants; I2 = 52%). Due to the substantial unexplained heterogeneity between studies, we downgraded the certainty of the evidence to moderate. In subgroup analysis, we found no evidence that the effect of telephone counselling depended upon whether or not other interventions were provided (P = 0.21), no evidence that more intensive support was more effective than less intensive (P = 0.43), or that the effect of telephone support depended upon whether or not people were actively trying to quit smoking (P = 0.32). However, in meta-regression, telephone counselling was associated with greater effectiveness when provided as an adjunct to self-help written support (P < 0.01), or to a brief intervention from a health professional (P = 0.02); telephone counselling was less effective when provided as an adjunct to more intensive counselling. Further, telephone support was more effective for people who were motivated to try to quit smoking (P = 0.02). The findings from three additional trials of smokers who had not proactively called a helpline but were offered telephone counselling, found quit rates were higher in those offered three to five telephone calls compared to those offered just one call (RR 1.27, 95% CI 1.12 to 1.44; 2602 participants; I2 = 0%).
AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that proactive telephone counselling aids smokers who seek help from quitlines, and moderate-certainty evidence that proactive telephone counselling increases quit rates in smokers in other settings. There is currently insufficient evidence to assess potential variations in effect from differences in the number of contacts, type or timing of telephone counselling, or when telephone counselling is provided as an adjunct to other smoking cessation therapies. Evidence was inconclusive on the effect of reactive telephone counselling, due to a limited number studies, which reflects the difficulty of studying this intervention.
BACKGROUND: Taking regular exercise, whether cardiovascular-type exercise or resistance exercise, may help people to give up smoking, particularly by reducing cigarette withdrawal symptoms and cravings, and by helping to manage weight gain.
OBJECTIVES: To determine the effectiveness of exercise-based interventions alone, or combined with a smoking cessation programme, for achieving long-term smoking cessation, compared with a smoking cessation intervention alone or other non-exercise intervention.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register for studies, using the term 'exercise' or 'physical activity' in the title, abstract or keywords. The date of the most recent search was May 2019.
SELECTION CRITERIA: We included randomised controlled trials that compared an exercise programme alone, or an exercise programme as an adjunct to a cessation programme, with a cessation programme alone or another non-exercise control group. Trials were required to recruit smokers wishing to quit or recent quitters, to assess abstinence as an outcome and have follow-up of at least six months.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Smoking cessation was measured after at least six months, using the most rigorous definition available, on an intention-to-treat basis. 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, as either smoking cessation or relapse prevention. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models.
MAIN RESULTS: We identified 24 eligible trials with a total of 7279 adult participants randomised. Two studies focused on relapse prevention among smokers who had recently stopped smoking, and the remaining 22 studies were concerned with smoking cessation for smokers who wished to quit. Eleven studies were with women only and one with men only. Most studies recruited fairly inactive people. Most of the trials employed supervised, group-based cardiovascular-type exercise supplemented by a home-based exercise programme and combined with a multi-session cognitive behavioural smoking cessation programme. The comparator in most cases was a multi-session cognitive behavioural smoking cessation programme alone. Overall, we judged two studies to be at low risk of bias, 11 at high risk of bias, and 11 at unclear risk of bias. Among the 21 studies analysed, we found low-certainty evidence, limited by potential publication bias and by imprecision, comparing the effect of exercise plus smoking cessation support with smoking cessation support alone on smoking cessation outcomes (RR 1.08, 95% CI 0.96 to 1.22; I2 = 0%; 6607 participants). We excluded one study from this analysis as smoking abstinence rates for the study groups were not reported. There was no evidence of subgroup differences according to the type of exercise promoted; the subgroups considered were: cardiovascular-type exercise alone (17 studies), resistance training alone (one study), combined cardiovascular-type and resistance exercise (one study) and type of exercise not specified (two studies). The results were not significantly altered when we excluded trials with high risk of bias, or those with special populations, or those where smoking cessation intervention support was not matched between the intervention and control arms. Among the two relapse prevention studies, we found very low-certainty evidence, limited by risk of bias and imprecision, that adding exercise to relapse prevention did not improve long-term abstinence compared with relapse prevention alone (RR 0.98, 95% CI 0.65 to 1.47; I2 = 0%; 453 participants).
AUTHORS' CONCLUSIONS: There is no evidence that adding exercise to smoking cessation support improves abstinence compared with support alone, but the evidence is insufficient to assess whether there is a modest benefit. Estimates of treatment effect were of low or very low certainty, because of concerns about bias in the trials, imprecision and publication bias. Consequently, future trials may change these conclusions.
BACKGROUND: 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 stop smoking.
OBJECTIVES: To evaluate the efficacy of MI for smoking cessation compared with no treatment, in addition to another form of smoking cessation treatment, and compared with other types of smoking cessation treatment. We also investigated whether more intensive MI is more effective than less intensive MI for smoking cessation.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised 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. We also searched trial registries to identify unpublished studies. Date of the most recent search: August 2018.
SELECTION CRITERIA: Randomised controlled trials in which MI or its variants were offered to smokers to assist smoking cessation. We excluded trials that did not assess cessation as an outcome, with follow-up less than six months, and with additional non-MI intervention components not matched between arms. We excluded trials in pregnant women as these are covered elsewhere.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Smoking cessation was measured after at least six months, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RR) and 95% confidence intervals (CI) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models. We extracted data on mental health outcomes and quality of life and summarised these narratively.
MAIN RESULTS: We identified 37 eligible studies involving over 15,000 participants who smoked tobacco. The majority of studies recruited participants with particular characteristics, often from groups of people who are less likely to seek support to stop smoking than the general population. Although a few studies recruited participants who intended to stop smoking soon or had no intentions to quit, most recruited a population without regard to their intention to quit. MI was conducted in one to 12 sessions, with the total duration of MI ranging from five to 315 minutes across studies. We judged four of the 37 studies to be at low risk of bias, and 11 to be at high risk, but restricting the analysis only to those studies at low or unclear risk did not significantly alter results, apart from in one case - our analysis comparing higher to lower intensity MI.We found low-certainty evidence, limited by risk of bias and imprecision, comparing the effect of MI to no treatment for smoking cessation (RR = 0.84, 95% CI 0.63 to 1.12; I2 = 0%; adjusted N = 684). One study was excluded from this analysis as the participants recruited (incarcerated men) were not comparable to the other participants included in the analysis, resulting in substantial statistical heterogeneity when all studies were pooled (I2 = 87%). Enhancing existing smoking cessation support with additional MI, compared with existing support alone, gave an RR of 1.07 (95% CI 0.85 to 1.36; adjusted N = 4167; I2 = 47%), and MI compared with other forms of smoking cessation support gave an RR of 1.24 (95% CI 0.91 to 1.69; I2 = 54%; N = 5192). We judged both of these estimates to be of low certainty due to heterogeneity and imprecision. Low-certainty evidence detected a benefit of higher intensity MI when compared with lower intensity MI (RR 1.23, 95% CI 1.11 to 1.37; adjusted N = 5620; I2 = 0%). The evidence was limited because three of the five studies in this comparison were at risk of bias. Excluding them gave an RR of 1.00 (95% CI 0.65 to 1.54; I2 = n/a; N = 482), changing the interpretation of the results.Mental health and quality of life outcomes were reported in only one study, providing little evidence on whether MI improves mental well-being.
AUTHORS' CONCLUSIONS: There is insufficient evidence to show whether or not MI helps people to stop smoking compared with no intervention, as an addition to other types of behavioural support for smoking cessation, or compared with other types of behavioural support for smoking cessation. It is also unclear whether more intensive MI is more effective than less intensive MI. All estimates of treatment effect were of low certainty because of concerns about bias in the trials, imprecision and inconsistency. Consequently, future trials are likely to change these conclusions. There is almost no evidence on whether MI for smoking cessation improves mental well-being.
BACKGROUND: Hypnotherapy is widely promoted as a method for aiding smoking cessation. It is intended to act on underlying impulses to weaken the desire to smoke, or strengthen the will to stop.
OBJECTIVES: To evaluate the effect and safety of hypnotherapy for smoking cessation.
SEARCH METHODS: For this update we searched the Cochrane Tobacco Addiction Group Specialized Register, and trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform), using the terms "smoking cessation" and "hypnotherapy" or "hypnosis", with no restrictions on language or publication date. The most recent search was performed on 18 July 2018.
SELECTION CRITERIA: We considered randomized controlled trials that recruited people who smoked and implemented a hypnotherapy intervention for smoking cessation compared with no treatment, or with any other therapeutic interventions. Trials were required to report smoking cessation rates at least six months after the beginning of treatment. Study eligibility was determined by at least two review authors, independently.
DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data on participant characteristics, the type and duration of hypnotherapy, the nature of the control group, smoking status, method of randomization, and completeness of follow-up. These authors also independently assessed the quality of the included studies. In undertaking this work, we used standard methodological procedures expected by Cochrane.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 abstinence rates where available. Those lost to follow-up were considered to still be smoking. We summarized effects as risk ratios (RRs) and 95% confidence intervals (CIs). Where possible, we performed meta-analysis using a fixed-effect model. We also noted any adverse events reported.
MAIN RESULTS: We included three new trials in this update, which brings the total to 14 included studies that compared hypnotherapy with 22 different control interventions. The studies included a total of 1926 participants. Studies were diverse and a single meta-analysis was not possible. We judged only one study to be at low risk of bias overall; we judged 10 studies to be at high risk of bias and three at unclear risk. Studies did not provide reliable evidence of a greater benefit from hypnotherapy compared with other interventions or no treatment for smoking cessation. Most individual studies did not find statistically significant differences in quit rates after six months or longer, and studies that did detect differences typically had methodological limitations.Pooling small groups of relatively comparable studies did not provide reliable evidence for a specific effect of hypnotherapy relative to controls. There was low certainty evidence, limited by imprecision and risk of bias, that showed no statistically significant difference between hypnotherapy and attention-matched behavioural treatments (RR 1.21, 95% CI 0.91 to 1.61; I2 = 36%; 6 studies, 957 participants). Results were similarly imprecise, and also limited by risk of bias, when comparing hypnotherapy to intensive behavioural interventions (not matched for contact time) (RR 0.93, 95% CI 0.47 to 1.82; I2 = 0%; 2 studies, 211 participants; very low certainty evidence). Results from one small study (40 participants) detected a statistically significant benefit of hypnotherapy compared to no intervention (RR 19.00, 95% CI 1.18 to 305.88), but this evidence was judged to be of very low certainty due to high risk of bias and imprecision. No significant differences were detected in comparisons of hypnotherapy with brief behavioural interventions (RR 0.98, 95% CI 0.57 to 1.69; I² = 0%; 2 studies, 269 participants), rapid/focused smoking (RR 1.00, 95% CI 0.43 to 2.33; I2 = 65%; 2 studies, 54 participants), and pharmacotherapies (RR 1.68, 95% CI 0.88 to 3.20; I2 = 5%; 2 studies, 197 participants). When hypnotherapy was evaluated as an adjunct to other treatments, the pooled result from five studies showed a statistically significant benefit in favour of hypnotherapy (RR 2.10, 95% CI 1.31 to 3.35; I² = 62%; 224 participants); however, this result should be interpreted with caution due to the high risk of bias across studies (four had a high risk or bias, one had an unclear risk), and substantial statistical heterogeneity.Most studies did not provide information on whether data specifically relating to adverse events were collected, and whether or not any adverse events occurred. One study that did collect such data did not find a statistically significant difference in the adverse event 'index' between hypnotherapy and relaxation.
AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether hypnotherapy is more effective for smoking cessation than other forms of behavioural support or unassisted quitting. If a benefit is present, current evidence suggests the benefit is small at most. There is very little evidence on whether hypnotherapy causes adverse effects, but the existing data show no evidence that it does. Further large, high-quality randomized controlled trials, and more comprehensive assessments of safety, are needed on this topic.
BACKGROUND: Pharmacotherapies for smoking cessation increase the likelihood of achieving abstinence in a quit attempt. It is plausible that providing support, or, if support is offered, offering more intensive support or support including particular components may increase abstinence further.
OBJECTIVES: To evaluate the effect of adding or increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. We also looked at studies which directly compare behavioural interventions matched for contact time, where pharmacotherapy is provided to both groups (e.g. tests of different components or approaches to behavioural support as an adjunct to pharmacotherapy).
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, clinicaltrials.gov, and the ICTRP in June 2018 for records with any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline, that evaluated the addition of personal support or compared two or more intensities of behavioural support.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount or type of behavioural support. The intervention condition had to involve person-to-person contact (defined as face-to-face or telephone). The control condition could receive less intensive personal contact, a different type of personal contact, written information, or no behavioural support at all. We excluded trials recruiting only pregnant women and trials which did not set out to assess smoking cessation at six months or longer.
DATA COLLECTION AND ANALYSIS: For this update, screening and data extraction followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically-validated rates, if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a random-effects model.
MAIN RESULTS: Eighty-three studies, 36 of which were new to this update, met the inclusion criteria, representing 29,536 participants. Overall, we judged 16 studies to be at low risk of bias and 21 studies to be at high risk of bias. All other studies were judged to be at unclear risk of bias. Results were not sensitive to the exclusion of studies at high risk of bias. We pooled all studies comparing more versus less support in the main analysis. Findings demonstrated a benefit of behavioural support in addition to pharmacotherapy. When all studies of additional behavioural therapy were pooled, there was evidence of a statistically significant benefit from additional support (RR 1.15, 95% CI 1.08 to 1.22, I² = 8%, 65 studies, n = 23,331) for abstinence at longest follow-up, and this effect was not different when we compared subgroups by type of pharmacotherapy or intensity of contact. This effect was similar in the subgroup of eight studies in which the control group received no behavioural support (RR 1.20, 95% CI 1.02 to 1.43, I² = 20%, n = 4,018). Seventeen studies compared interventions matched for contact time but that differed in terms of the behavioural components or approaches employed. Of the 15 comparisons, all had small numbers of participants and events. Only one detected a statistically significant effect, favouring a health education approach (which the authors described as standard counselling containing information and advice) over motivational interviewing approach (RR 0.56, 95% CI 0.33 to 0.94, n = 378).
AUTHORS' CONCLUSIONS: There is high-certainty evidence that providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking increases quit rates. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 20%, based on a pooled estimate from 65 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support. More research is needed to assess the effectiveness of specific components that comprise behavioural support.
The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES:
To assess the evidence for the efficacy, harms, 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 Group Specialised Register, most recently on 29 April 2022.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms.
DATA COLLECTION AND ANALYSIS:
We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms 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 dropouts due to treatment. We carried out meta-analyses where appropriate.
MAIN RESULTS:
We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I2 = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I2 = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I2 = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I2 = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I2 = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I2 = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I2 = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I2 = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I2 = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I2 = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I2 = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I2 = 0%; 10 studies, 7613 participants). We also found 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), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I2 = 0%; 3 studies, 417 participants), although this result was subject to imprecision. 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 may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. 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 other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
