Importance: It has been estimated that in 2018 nearly 20%of adults in the US were currently using a tobacco product.

Objective: To systematically review the effectiveness and safety of pharmacotherapy, behavioral interventions, and electronic cigarettes for tobacco cessation among adults, including pregnant persons, to inform the US Preventive Services Task Force.

Data Sources: PubMed, PsycInfo, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Centre for Reviews and Dissemination of Health Technology Assessment; surveillance through September 25, 2020.

Study Selection: Systematic reviews of tobacco cessation interventions and randomized clinical trials that evaluated the effects of electronic cigarettes (e-cigarettes) or pharmacotherapy among pregnant persons.

Data Extraction and Synthesis: Independent critical appraisal and data abstraction; qualitative synthesis and random-effects meta-analyses.

Main Outcomes and Measures: Health outcomes, tobacco cessation at 6 months or more, and adverse events.

Results: Sixty-seven reviews addressing pharmacotherapy and behavioral interventions were included as well as 9 trials (N = 3942) addressing e-cigarettes for smoking cessation and 7 trials (N = 2285) of nicotine replacement therapy (NRT) use in pregnancy. Combined pharmacotherapy and behavioral interventions (pooled risk ratio [RR], 1.83 [95% CI, 1.68-1.98]), NRT (RR, 1.55 [95% CI, 1.49-1.61]), bupropion (RR, 1.64 [95% CI, 1.52-1.77]), varenicline (RR, 2.24 [95% CI, 2.06-2.43]), and behavioral interventions such as advice from clinicians (RR, 1.76 [95% CI, 1.58-1.96]) were all associated with increased quit rates compared with minimal support or placebo at 6 months or longer. None of the drugs were associated with serious adverse events. Five trials (n = 3117) reported inconsistent findings on the effectiveness of electronic cigarettes on smoking cessation at 6 to 12 months among smokers when compared with placebo or NRT, and none suggested higher rates of serious adverse events. Among pregnant persons, behavioral interventions were associated with greater smoking cessation during late pregnancy (RR, 1.35 [95% CI, 1.23-1.48]), compared with no intervention. Rates of validated cessation among pregnant women allocated to NRT compared with placebo were not significantly different (pooled RR, 1.11 [95% CI, 0.79-1.56], n = 2033).

Conclusions and Relevance: There is strong evidence that a range of pharmacologic and behavioral interventions, both individually and in combination, are effective in increasing smoking cessation in nonpregnant adults. In pregnancy, behavioral interventions are effective for smoking cessation, but data are limited on the use of pharmacotherapy for smoking cessation. Data on the effectiveness and safety of electronic cigarettes for smoking cessation among adults are also limited and results are inconsistent.

Despite progress in reducing the use of tobacco products by US adults, in 2019 an estimated 20.8% of adults in the US currently used any tobacco product and there are persistent differences in rates of smoking by age, sex, and race/ethnicity.¹ A large range of pharmacologic and behavioral methods are available to help adults quit tobacco use;² however in a 2015 survey, among those who tried quitting in the previous year, only 31.2% reported using evidence-based cessation treatments and 7.4% were successful in quitting.³

In 2015, the US Preventive Services Task Force (USPSTF) issued 4 recommendations related to tobacco cessation interventions among adults. Two A recommendations were given for behavioral and pharmacotherapy interventions for adults and for behavioral interventions for pregnant women, and 2 I statements were issued: one for pharmacotherapy interventions for pregnant women and one on the use of electronic cigarettes (e-cigarettes) for tobacco cessation among adults and pregnant women.⁴ The objective of this review was to inform updated recommendations by the USPSTF.

Scope of Review

This is an update of a 2015 overview of reviews that supported the 2015 USPSTF recommendation.^5,6 An analytic framework and 3 key questions (KQs) guided the review (Figure). Consistent with the 2015 review, an overview of reviews method was primarily used for this update. However, given the insufficient evidence found in 2015, original searches and syntheses of primary evidence were conducted for the benefits and harms of e-cigarettes for smoking cessation and for the benefits and harms of pharmacologic smoking cessation interventions among pregnant women. Details are available in the full report.⁸ All main results presented in the full report are also presented in this article; more detailed methods, including review selection and determination of overall credibility and quality of individual reviews and studies, and additional effect estimates for specific types of interventions and comparative effectiveness outcomes, are provided in the full report.

Data Sources and Searches

Three separate literature searches were conducted. All searches were restricted to articles in the English language published since January 2014. For reviews, the following databases were searched through April 2019: PubMed, PsycINFO, the Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews (CDSR), and the Centre for Reviews and Dissemination Health Technology Assessment. For primary evidence on e-cigarettes, the CDSR, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), PsycInfo, PubMed, and Scopus were searched through May 2020. For studies of pharmacotherapy tobacco cessation interventions among pregnant women, Medline, CENTRAL, PubMed, and PsycInfo were searched through May 2020. Ongoing surveillance for relevant primary literature and Cochrane systematic reviews was completed through September 25, 2020.

Study Selection

Two researchers independently reviewed all identified abstracts and full-text articles against prespecified eligibility criteria. Studies were included if they were systematic reviews, with or without meta-analysis, that examined the effectiveness of tobacco cessation interventions for adults. Interventions targeting cessation of any tobacco product, including e-cigarettes, were included and reviews that focused on specific interventions (eg, nicotine replacement therapy [NRT], group counseling) and specific subpopulations (eg, persons with serious mental illness) were eligible. Reviews published by Cochrane and non-Cochrane reviews were included. Narrative (nonsystematic) reviews and other overviews of reviews were excluded. Only the most recent version of updated reviews was included. Separate inclusion criteria were outlined when considering primary evidence related to e-cigarettes and pharmacotherapy interventions among pregnant women.

Data Extraction and Quality Assessment

One reviewer completed the AMSTAR-2 (Assessment of Multiple Systematic Reviews 2) tool⁹ to rate the credibility of the systematic reviews under consideration for inclusion, and a second reviewer provided an independent assessment using the same tool for all reviews rated critically low. For primary studies, 2 reviewers independently assessed the risk of bias of included evidence using study-design specific criteria. Each review and study were assigned a quality rating of “good,” fair,” or “poor” according to the USPSTF study design–specific criteria.⁷ Reviews rated as having critically low credibility and primary studies rated as poor quality were excluded. Data from each included review and primary study were abstracted into detailed abstraction forms using DistillerSR. For all included evidence, one reviewer completed primary data abstraction and a second reviewer checked all data for accuracy and completeness.

Data Synthesis and Analysis

Given the large number of reviews that met eligibility criteria and the overlapping scope and evidence between many of them, a method was developed to identify 1 or more reviews within each population and intervention group that represented the most current and applicable evidence. These reviews served as the basis for the main findings. All other reviews were examined for complementary or discordant findings. Pooled point estimates presented in the included reviews were reported when appropriate; none of the individual study evidence was reanalyzed. Data from trials of e-cigarette use were not meta-analyzed, given the few number of studies and data reporting. Methods for the meta-analyses of data from trials of pharmacotherapy among pregnant women are described in the full evidence report.

For the overview of reviews method, the strength of the overall body of evidence assigned within the primary systematic review was reported. In most cases, these grades were based on the Grading of Recommendations Assessment, Development and Evaluation working group definitions, which consider study limitations, consistency of effect, imprecision, indirectness, and publication bias. Where strength of evidence grades were not available, including for the primary evidence syntheses, an overall strength of evidence grade was assigned based on consensus discussions involving at least 2 reviewers.¹⁰

This review addressed 2 populations of interest: the general adult population and pregnant women. Within each population, results are organized by KQ.

For the overview of reviews, investigators reviewed 1173 abstracts and 210 full-text articles for possible inclusion for all KQs. Sixty-four reviews were identified that met eligibility criteria, including those among an unselected population of adults and those limited to a specific subgroup of adults (Table 1).^11-53,57-77 Thirty-two reviews were designated as primary reviews.^{11-16,18-20,22,24-30,32-34,38,41,43,45,46,48-53,78} Eleven additional reviews had overlapping evidence with the primary reviews.^{17,21,23,31,35,37,39,40,42,44,47} Results of these reviews were consistent with the primary reviews in terms of effect magnitude and statistical significance and are not discussed further. Twenty-one reviews focused on specific subpopulations of adults (eg, people with severe mental illness, smokeless tobacco users).^57-77 These 21 reviews are not discussed here but are included in the full report.⁸

The review of primary evidence on the use of e-cigarettes for smoking cessation resulted in 9 included randomized clinical trials (RCTs) reported in 16 publications; 5 of these RCTs addressed smoking cessation (KQ2) and all addressed potential harms (KQ3).^79-94 None of the e-cigarette trials reported results related to health outcomes (KQ1).

Health Benefits of Interventions

Key Question 1. Do tobacco cessation interventions improve mortality, morbidity, and other health outcomes in adults who currently use tobacco?

One RCT (n = 1445) reported the results of a behavioral tobacco cessation intervention on health outcomes.⁹⁵ This study reported no statistically significant differences between intervention and control groups in rates of total mortality (41.5% vs 44.%, P = .93), coronary heart disease mortality (17.3% vs 19.9%, P = .87), and lung cancer incidence (7.8% vs 8.8%, P = .89) at 20-year follow-up among men at high risk for cardiorespiratory disease.⁹⁶

Cessation Benefits of Interventions

Key Question 2. Do tobacco cessation interventions increase tobacco abstinence in adults who currently use tobacco?

Among the general adult population, there was strong evidence from systematic reviews that the combination of pharmacotherapy and behavioral support, all 7 US Food and Drug Administration–approved medications (all forms of NRT, bupropion, varenicline), and a variety of behavioral interventions were statistically significantly associated with an increase in smokers’ relative likelihood to quit smoking at 6 or more months as compared with smokers receiving usual care or a minimal stop-smoking intervention (Table 2).

The pooled risk ratio (RR) for smoking abstinence at 6 months or more for combined pharmacotherapy plus behavioral support vs usual care or minimal support control groups was 1.83 (95% CI, 1.68- 1.98; 52 trials; n = 19,488).¹¹ Average quit rates in these trials ranged from 2% to 50% (mean, 15.2%) among participants receiving pharmacotherapy and behavioral support vs 0% to 36% (mean, 8.6%) among participants randomized to a control group.

There was also evidence of an association between the use of NRTs, bupropion, and varenicline and smoking abstinence at 6 months or more (Table 2). The pooled RR for abstinence for NRT was 1.55 (95% CI, 1.49-1.61; 133 trials; n = 64,640);¹² for bupropion, 1.64 (95% CI, 1.52-1.77; 46 trials; n = 17,866);¹⁵ and for varenicline, 2.24 (95% CI, 2.06-2.43; 27 trials; n = 12,625)¹⁶ when compared with placebo or no drug. In all cases, behavioral support to quit smoking was provided to both intervention and control participants. There was also an association between combined NRT (typically a long- and short-acting therapy) and quitting at 6 months or more (RR, 1.25 [95% CI, 1.15-1.36]; 14 trials; n = 11,356) compared with a single form of NRT.¹³ Pooled analysis of trials directly comparing NRT and bupropion did not suggest a difference between the 2 types of pharmacotherapy (RR, 0.99 [95% CI, 0.91-1.09]; 10 trials; n = 8230);¹⁵ however, varenicline has been shown to be superior to both NRT (RR, 1.25 [95% CI, 1.14-1.37]; 8 trials; n = 6264)¹⁶ and bupropion (RR [bupropion vs varenicline], 0.71 [95% CI, 0.64-0.79]; 6 trials; n = 6286)¹⁵ in achieving abstinence at 6 months or more, although there are fewer trials testing these differences. There is limited evidence for the use of other antidepressants and nicotine receptor partial agonists for their effectiveness in helping people stop smoking.^15,16

Compared with various controls, behavioral interventions such as in-person advice and support from clinicians;^26,27 individual-,²⁸ group-,²⁹ telephone-,³⁴ and mobile phone–based³⁸ support; interactive and tailored internet-based interventions;⁴¹ and the use of incentives⁴³ were associated with increased relative smoking cessation at 6 or more months (15% to 88% range of relative effects). Pooled results for all comparisons are reported in Table 2. For example, smoking cessation advice from a physician or nurse was associated with pooled RRs of 1.76 (95% CI, 1.58-1.96; 28 trials; n = 22,239)²⁶ and 1.29 (95% CI, 1.21- 1.38; 44 trials; n = 20,881),²⁷ respectively. Behavioral support, when added to pharmacotherapy, was also associated with increased rates of smoking cessation when compared with pharmacotherapy alone (RR, 1.15 [95% CI, 1.08-1.22]; 65 trials; n = 23,331).²⁵ There was a lack of clear benefit of motivational interviewing;³⁰ decision aids;³² real-time video counseling;³⁶ print-based, nontailored self-help materials;³³ biomedical risk assessment;⁴⁵ exercise;⁴⁶ acupuncture;⁴⁸ hypnotherapy;⁴⁹ and systems-level interventions^50,51 compared with controls; however, there was substantially less evidence related to each of these interventions, and many individual trials of these interventions showed positive effects.

There was no evidence to suggest that the benefits and harms of pharmacotherapy and behavioral interventions, alone and combined, differed when offered to specific subpopulations of adults, including those with mental health conditions, ethnic minorities, or smokeless tobacco users. Where pooled results were presented, the direction and magnitude of effects were almost identical to those seen with the broader evidence base, although very few direct comparisons between subgroups were presented. While some reviews found evidence of potential effect modification by specific intervention, population, or study design characteristics, there was no individual factor that consistently predicted greater treatment effects across reviews.

Five trials (n = 3117)^{80,81,90,91,93} were included that evaluated the effectiveness of using e-cigarettes to help current conventional smokers stop or reduce smoking compared with placebo or nicotine replacement therapy. The types of e-cigarettes, nicotine content, delivery of the intervention, and additional intervention components differed across all 5 trials, as did the comparisons. Mixed findings were reported on the effectiveness of e-cigarettes on smoking cessation at 6 to 12 months among adult smokers when compared with placebo devices or NRT. In 2 of the 5 trials (n = 2008), smokers randomized to e-cigarettes containing nicotine (with or without the co-use of NRT) were found to have statistically significantly greater rates of abstinence than those randomized to NRT alone⁹⁰ or NRT plus nonnicotine e-cigarettes⁹¹ at 6- to 12-month follow-up. In both trials, continued use of e-cigarettes was high at 6- and 12-month follow-up (approximately 3-9 months after the treatment phase), with 45% to 80% of participants still using nicotine-based e-cigarettes as opposed to approximately 9% to 40% of participants still using NRT. Another trial (n = 300) compared the use of e-cigarettes (2 groups using different nicotine concentrations) with placebo at 12 months and found 11% abstinence in the nicotine-containing e-cigarette groups compared with 4% abstinence in the placebo group (P = .04), but 27% of those who quit smoking continued to use e-cigarettes at 1 year.⁸¹ The remaining 2 trials (n = 807) reported no clear difference in the rates of smoking cessation among those randomized to nicotine e-cigarettes vs placebo e-cigarettes⁸⁰ or nicotine gum at 6 to 12 months’ follow-up.⁹³

Harms of Interventions

Key Question 3. What harms are associated with tobacco cessation interventions in adults? 

Nine primary reviews reported adverse events related to pharmacotherapy interventions for smoking cessation in general adult populations.^{12-16,18-20,22} There was no association between the use of NRT, bupropion, or varenicline and serious adverse events, including major cardiovascular adverse events or serious neuropsychiatric events, as compared with placebo or nondrug control groups. Few reviews on behavioral interventions captured information on potential harms, and none suggested serious adverse events that arose. Nine trials reported on the potential short-term harms of e-cigarette use for cessation; none suggested relatively higher rates of serious adverse events.^{80-84,86,90,91,93}

Based on a primary literature review of 64 full-text articles, 7 RCTs (n = 2285) (reported in 12 publications)^98-109 that evaluated the use of NRT among pregnant women were included. Additionally, 5 large observational studies (n = 1,293,379) (reported in 6 publications)^110-115 were included that reported on the harms of NRT, bupropion, or varenicline use.

Using the overview of reviews approach, 5 reviews were identified that addressed the benefits and harms of behavioral interventions for supporting women to stop smoking during pregnancy (Table 1).^43,53-56 A 2017 Cochrane review included the most comprehensive evidence synthesis of tobacco cessation behavioral support interventions for pregnant women and was used as the basis for the findings presented here.⁵⁴ The other identified reviews were mostly duplicative and the results were entirely consistent with the Cochrane review.

No studies were identified that addressed the benefits or harms of the use of e-cigarettes to help pregnant women quit smoking.

Health Benefits of Interventions

Key Question 1. Do tobacco cessation interventions improve mortality, morbidity,and other health outcomes in pregnant women who currently use tobacco?

All 7 included RCTs (n = 2285) were designed to test the effectiveness of NRT on smoking cessation and reported infant, child, and maternal health.^{98,99,102,105-107,109} Five placebo-controlled trials reported on preterm birth (delivery at <37 weeks’ gestation).^{98,99,105,106,109} The most recent study, conducted in 2017, reported a statistically significant lower incidence of preterm delivery among those in the NRT inhaler group (3/67 [4.5%]) compared with the placebo group (10/67 [14.9%]) (P = .03) after controlling for history of preterm birth.¹⁰⁶ Within the other trials, 1 (n = 403) reported similar numbers of women with preterm birth in the NRT and placebo groups (14.0% vs 13.5%, respectively),⁹⁸ 2 (n = 1301) reported only slightly fewer women with preterm birth in the NRT group,^99,109 and the study with the fewest patients (n = 194) reported reduced incidence of preterm birth with NRT compared with placebo (RR, 0.39 [95% CI, 0.17-0.91]).¹⁰⁵ The 3 placebo-controlled trials that did not report statistically significant differences had larger samples and estimated effects closer to null, with RRs ranging from 0.85 to 1.04.^98,99,109 Two trials without placebo controls were imprecise (very wide CIs) and estimated effects in opposite directions.^102,107

All 7 trials reported the association between NRT and mean birth weight.^{98,99,102,105-107,109} Two placebo-controlled trials found significantly higher mean birth weights among women allocated to the NRT group,^105,109 and only one of these trials¹⁰⁵ reported similar effect for the proportion of infants categorized as having low birth weight. The 2 largest, good-quality, placebo-controlled trials of NRT patch interventions (n = 403 and n = 1051) did not find evidence of increased infant birth weight with NRT treatment.^98,99

One hundred two RCTs were included in a 2017 review that addressed the effects of behavioral smoking cessation interventions during pregnancy on smoking behavior and perinatal health outcomes.⁵⁴ Of the 102 included trials, 19 study groups reported rates of preterm birth (<37 weeks’ gestation), 26 study groups reported mean birth weight, and 17 groups reported rates of low birth- weight infants (<2500 g).⁵⁴ Other, less commonly reported data included stillbirths (8 trials), perinatal deaths (4 trials), and neonatal deaths (5 trials) (results related to these outcomes are included in the full report).

Of the 19 trials reporting the effects of a behavioral intervention on preterm birth (less than 37 weeks’ gestation), results were mixed, although the majority reported a reduced risk of preterm birth among women within the behavioral interventions vs control groups.⁵⁴ The review’s meta-analysis of these trials found no significant association with behavioral interventions compared with controls on rates of preterm birth (RR, 0.93 [95% CI 0.77- 1.11]; 19 trials; n = 9222). When all 26 studies that reported mean birth weight were combined, there was evidence that behavioral smoking cessation interventions were associated with a higher mean birth weight (55.60 g, compared with usual care control interventions; mean difference, 55.60 g [95% CI, 29.82-81.38]; 26 trials; n = 11,338).⁵⁴ A pooled analysis of 18 RCTs also found a 17% risk reduction for delivery of a low-birth-weight infant (<2500 g) (RR, 0.83 [95% CI, 072-0.94]; 18 trials; n = 9402).

Cessation Benefits of Interventions

Key Question 2. Do tobacco cessation interventions increase tobacco abstinence in pregnant women who currently use tobacco?

There was no evidence of differences in rates of smoking cessation among pregnant women randomized to NRT vs placebo or no intervention within the included trials. Meta-analysis of 5 placebo-controlled trials found a pooled RR of 1.11 (95% CI, 0.79- 1.56]; n = 2033) for NRT vs placebo.^{98,99,105,106,109} Quit rates in these trials ranged from 5% to 28% in the intervention groups and 5% to 25% in the control groups (mean, 11.8% vs 10.6%). The results of the 2 smaller trials with no treatment controls^102,107 were not statistically significant, and estimates of efficacy were greater than for the placebo-controlled trials.

Within the Cochrane review on behavioral interventions among pregnant women, of the 120 study groups included in the review, 97 groups reported the primary outcome measure of smoking abstinence in late pregnancy, up to and including the period of hospitalization for birth.⁵⁴ Pooled analyses of all behavioral interventions, regardless of type of behavioral support and including self-reported outcomes, indicated a statistically significant association with smoking cessation in late pregnancy when compared with usual care or a minimal intervention (RR, 1.35 [95% CI, 1.23-1.48]; 97 trials; n = 26,637). The results were similarly associated with a beneficial effect when restricted to trials comparing counseling with usual care (RR, 1.44 [95% CI, 1.19-1.73]; 30 trials; n = 12,432). There was some evidence that the positive association of behavioral interventions on smoking cessation in late pregnancy continued into the postpartum period, up until approximately 18 months postpartum. For instance, in an examination of counseling interventions compared with usual care, the average RR was 1.59 (95% CI, 1.26-2.01; 11 trials) at 0 to 5 months postpartum, 1.33 (95% CI, 1.00-1.77; 6 trials) at 6 to 11 months postpartum, and 2.20 (95% CI, 1.23-3.96; 2 trials) at 12 to 17 months.⁵⁴

Harms of Interventions

Key Question 3. What harms are associated with tobacco cessation interventions in pregnant women?

There was no evidence of perinatal harms related to NRT use among pregnant women, but data for assessing rare harms were very limited.^{98,99,102,105-107,109} Two larger trials reported stillbirths and congenital malformations and reported few events and no differences in the outcome between study groups.^98,99 Trials reporting miscarriage^98,99,106 and neonatal deaths^98,99,105 reported few events and no difference between study groups. One trial provided extended follow-up and did not find differences in longer-term developmental or respiratory harms associated with NRT use during pregnancy.¹⁰¹ Evidence from 5 large cohort studies did not find differences in stillbirth, birth outcomes, or any congenital anomaly for infants born to mothers with exposure to NRT, bupropion, or varenicline vs those unexposed to medications but whose mothers smoked.^110-115 Behavioral smoking cessation interventions were found to have minimal adverse effects.⁵⁴

This evidence review evaluated interventions for tobacco cessation in adults; the evidence is summarized in Table 3. The results are generally consistent with the conclusions of the 2020 Surgeon General’s report on smoking cessation.² There is moderate to high-certainty evidence that all 7 US Food and Drug Administration–approved medications for smoking cessation, a variety of behavioral support and counseling approaches, and the combination of pharmacotherapy plus behavioral support—all interventions that may be readily available to primary care patients and clinicians—can significantly increase the rate of smoking cessation among adults at 6 months and longer compared with usual care or brief self-help materials. Treatment effects appear to be comparable in a range of populations, settings, and types of behavioral support. Furthermore, despite adding nearly 5 more years of research since the previous review,^5,6 the effect estimates for each pooled comparison have been remarkably stable for at least the past 3 decades.

Nevertheless, various questions about tobacco cessation interventions have not yet been answered. Evidence is still needed to compare different forms, doses, and durations of drugs; to compare drugs with one another; to evaluate remotely delivered interventions vs minimal support; and to test interventions in special populations for which the effectiveness may differ from that in the general population (eg, pregnant women, persons with current severe mental illness, those with physical disabilities, nondaily and intermittent smokers), including direct subgroup comparisons.

Evidence on the potential benefits and harms of pharmacotherapy for smoking cessation during pregnancy is limited, with few placebo-controlled trials and limited power for detecting both potential benefits and harms (Table 3). In contrast to the findings in this review, a recent Cochrane review concluded that there was low-quality evidence suggesting that NRT may be more effective than placebo and nonplacebo controls.¹¹⁷ There was unclear evidence of an association when limited to only placebo-controlled trials,¹¹⁷ however, a finding similar to this review. Careful collection of adverse events information, including long-term consequences of stop-smoking medications, is important in future trials, and data on adherence to medications and levels of nicotine exposure from NRT relative to what occurs with smoking would also be valuable.

In contrast to the robust evidence on pharmacotherapy and behavioral interventions for smoking cessation, evidence on the use of e-cigarettes as an intervention to quit conventional smoking is lacking (Table 3). No studies on the use of e-cigarettes as tobacco cessation interventions reported health outcomes, and few trials reported on the potential adverse events of e-cigarette use when used in attempts to quit smoking. This is particularly concerning given the apparent longer-term use of e-cigarettes for cessation compared to pharmacotherapy in addition to the recent outbreak of e-cigarette, or vaping, product use–associated lung injury.¹¹⁸ Furthermore, there is lack of long-term epidemiologic studies and large clinical trials examining the associations between e-cigarette use and morbidity and mortality, especially in the long term.¹¹⁹

Although this review was scoped to include interventions focused on quitting any tobacco product, most published trials have targeted (and reported) quitting combustible cigarette use. More research is needed on interventions to help people quit other tobacco products such as cigars, smokeless tobacco, and e-cigarettes. Given the high prevalence of dual use of combustible and electronic cigarettes,¹²⁰ there is a need for research on interventions to help dual users of conventional cigarettes and e-cigarettes quit both products, as well as research on potential relapse back to cigarette use among former smokers who use e-cigarettes.

Limitations

The primary limitation of the evidence report relates to the overview of reviews approach. The comprehensiveness of the overview of reviews is inevitably limited by the recency and quality of the source reviews. Although most of the reviews included evidence at least through 2015, there may be evidence on specific population and intervention subsets that has been published after each review’s last search date. If this occurred, the respective bodies of evidence may not reflect these newer studies. Given the consistency of the effects within each group over time, however, it appears unlikely that any new trials, regardless of their sample size and effect estimates, would have substantial bearing on the overall results of this overview of reviews.

There is strong evidence that a range of pharmacologic and behavioral interventions, both individually and in combination, are effective in increasing smoking cessation in nonpregnant adults. In pregnancy, behavioral interventions are effective for smoking cessation, but data are limited on the use of pharmacotherapy for smoking cessation. Data on the effectiveness and safety of electronic cigarettes for smoking cessation among adults are also limited and results are inconsistent.

Source:This article was published in JAMA on January 19, 2021 (JAMA. 2021;325(3):280-298. doi:10.1001/jama.2020.23541).

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under contract HHSA-290-2015-00007-I-EPC5, Task Order 5, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Information: A draft version of this evidence report underwent external peer review from 6 content experts (Brian King, PhD, MPH [Centers for Disease Control and Prevention], Janet Wright, MD [Office of the Surgeon General], Nicola Lindson, BSc, MSc, CPsychol, PhD [University of Oxford], Stephen Fortmann, MD [Kaiser Permanente Center for Health Research], Nancy Rigotti, MD [Harvard Medical School], and Michele Levine, PhD [University of Pittsburgh]) and 3 federal partners (Centers for Disease Control and Prevention, National Institutes of Health, and US Food and Drug Administration). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

1. Cornelius ME, Wang TW, Jamal A, Loretan CG, Neff LJ. Tobacco product use among adults—United States, 2019. MMWR Morb Mortal Wkly Rep. 2020; 69(46):1736-1742. doi:10.15585/mmwr.mm6946a4
2. US Department of Health and Human Services. Smoking Cessation: A Report of the Surgeon General. US Dept of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2020.
3. Babb S, Malarcher A, Schauer G, Asman K, Jamal A. Quitting smoking among adults—United States, 2000-2015. MMWR Morb Mortal Wkly Rep. 2017;65(52):1457-1464. doi:10.15585/mmwr.mm6552a1
4. Siu AL; US Preventive Services Task Force. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(8):622-634. doi:10.7326/M15-2023
5. Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral counseling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;163(8):608-621. doi:10.7326/M15-0171
6. Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force. Agency for Healthcare Research and Quality; 2015.
7. Procedure Manual. US Preventive Services Task Force. Published 2015. Accessed May 22, 2019. https://www.uspreventiveservicestaskforce.org/uspstf/procedure-manual
8. Patnode CD, Henderson JT, Melknikow J, Coppola EL, Durbin S, Thomas R. Interventions for Tobacco Cessation in Adults, Including Pregnant Women: An Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 196. Agency for Healthcare Research and Quality; 2021. AHRQ publication 20-05264-EF-1.
9. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. doi:10.1136/bmj.j4008
10. Berkman ND, Lohr KN, Ansari M, et al. Grading the strength of a body of evidence when assessing health care interventions for the Effective Health Care Program of the Agency for Healthcare Research and Quality: an update. In: Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Agency for Healthcare Research and Quality;2014:314- 349. AHRQ publication 10(14)-EHC063-EF.
11. Stead LF, Koilpillai P, Fanshawe TR, Lancaster T. Combined pharmacotherapy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev. 2016;3(3):CD008286. doi:10.1002/14651858.CD008286.pub3
12. Hartmann-Boyce J, Chepkin SC, Ye W, Bullen C, Lancaster T. Nicotine replacement therapy versus control for smoking cessation. Cochrane Database Syst Rev. 2018;5(5):CD000146. doi:10.1002/14651858.CD000146.pub5
13. Lindson N, Chepkin SC, Ye W, Fanshawe TR, Bullen C, Hartmann-Boyce J. Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019;4(4):CD013308. doi:10.1002/14651858.CD013308
14. Mills EJ,Wu P, Lockhart I, Wilson K, Ebbert JO. Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation: a systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tob Induc Dis. 2010;8:8. doi:10.1186/1617-9625-8-8
15. Howes S, Hartmann-Boyce J, Livingstone-Banks J, Hong B, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2020;4(4):CD000031.
16. Cahill K, Lindson-Hawley N, Thomas KH, Fanshawe TR, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2016;(5):CD006103. doi:10.1002/14651858.CD006103.pub7
17. Agboola SA, Coleman T, McNeill A, Leonardi-Bee J. Abstinence and relapse among smokers who use varenicline in a quit attempt-a pooled analysis of randomized controlled trials. Addiction. 2015;110(7):1182-1193. doi:10.1111/add.12941
18. Sterling LH, Windle SB, Filion KB, Touma L, Eisenberg MJ. Varenicline and adverse cardiovascular events: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5(2):e002849. doi:10.1161/JAHA.115.002849
19. Thomas KH, Martin RM, Knipe DW, Higgins JP, Gunnell D. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ. 2015;350:h1109. doi:10.1136/bmj.h1109
20. Chang PH, Chiang CH, Ho WC, Wu PZ, Tsai JS, Guo FR. Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials. BMC Public Health. 2015;15:689. doi:10.1186/s12889-015-2055-0
21. Windle SB, Filion KB, Mancini JG, et al. Combination therapies for smoking cessation: a hierarchical Bayesian meta-analysis. Am J Prev Med. 2016;51(6):1060-1071. doi:10.1016/j.amepre.2016.07.011
22. Mills EJ, Thorlund K, Eapen S, Wu P, Prochaska JJ. Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. Circulation. 2014;129(1):28-41. doi:10.1161/CIRCULATIONAHA.113.003961
23. Rosen LJ, Galili T, Kott J, Goodman M, Freedman LS. Diminishing benefit of smoking cessation medications during the first year: ameta-analysis of randomized controlled trials. Addiction. 2018;113(5):805-816. doi:10.1111/add.14134
24. Hollands GJ, Naughton F, Farley A, Lindson N, Aveyard P. Interventions to increase adherence to medications for tobacco dependence. Cochrane Database Syst Rev. 2019;8(8):CD009164. doi:10.1002/14651858.CD009164.pub3
25. Hartmann-Boyce J, Hong B, Livingstone-Banks J, Wheat H, Fanshawe TR. Additional behavioural support as an adjunct to pharmacotherapy for smoking cessation. Cochrane Database Syst Rev. 2019;6(6):CD009670. doi:10.1002/14651858.CD009670.pub4
26. Stead LF, Buitrago D, Preciado N, Sanchez G, Hartmann-Boyce J, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev. 2013;(5):CD000165.
27. Rice VH, Heath L, Livingstone-Banks J, Hartmann-Boyce J. Nursing interventions for smoking cessation. Cochrane Database Syst Rev. 2017;12(12):CD001188.
28. Lancaster T, Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev. 2017;3(3):CD001292.
29. Stead LF, Carroll AJ, Lancaster T. Group behaviour therapy programmes for smoking cessation. Cochrane Database Syst Rev. 2017;3(3): CD001007. doi:10.1002/14651858.CD001007.pub3
30. Lindson N, Thompson TP, Ferrey A, Lambert JD, Aveyard P. Motivational interviewing for smoking cessation. Cochrane Database Syst Rev. 2019;7(7):CD006936.
31. Denison E, Underland V, Mosdol A, Vist G. Cognitive Therapies for Smoking Cessation: A Systematic Review. Knowledge Centre for the Health Services at the Norwegian Institute of Public Health (NIPH); 2017.
32. Moyo F, Archibald E, Slyer JT. Effectiveness of decision aids for smoking cessation in adults: a quantitative systematic review. JBI Database System Rev Implement Rep. 2018;16(9):1791-1822. doi:10.11124/JBISRIR-2017-003698
33. Livingstone-Banks J, Ordóñez-Mena JM, Hartmann-Boyce J. Print-based self-help interventions for smoking cessation. Cochrane Database Syst Rev. 2019;1(1):CD001118.
34. MatkinW, Ordóñez-Mena JM, Hartmann-Boyce J. Telephone counselling for smoking cessation. Cochrane Database Syst Rev. 2019;5(5):CD002850.
35. Danielsson AK, Eriksson AK, Allebeck P. Technology-based support via telephone or web: a systematic review of the effects on smoking, alcohol use and gambling. Addict Behav. 2014;39(12):1846-1868. doi:10.1016/j.addbeh.2014.06.007
36. Tzelepis F, Paul CL, Williams CM, et al. Real-time video counselling for smoking cessation. Cochrane Database Syst Rev. 2019;2019(10):CD012659.
37. Palmer M, Sutherland J, Barnard S, et al. The effectiveness of smoking cessation, physical activity/diet and alcohol reduction interventions delivered by mobile phones for the prevention of non-communicable diseases: a systematic review of randomised controlled trials. PLoS One. 2018;13(1):e0189801. doi:10.1371/journal.pone.0189801
38. Whittaker R, McRobbie H, Bullen C, Rodgers A, Gu Y, Dobson R. Mobile phone text messaging and app-based interventions for smoking cessation. Cochrane Database Syst Rev. 2019;10(10):CD006611. doi:10.1002/14651858.CD006611.pub5
39. Do HP, Tran BX, Le Pham Q, et al. Which eHealth interventions are most effective for smoking cessation? a systematic review. Patient Prefer Adherence. 2018;12:2065-2084. doi:10.2147/ PPA.S169397
40. McCrabb S, Baker AL, Attia J, et al. Internet-based programs incorporating behavior change techniques are associated with increased smoking cessation in the general population: a systematic review and meta-analysis. Ann Behav Med. 2019;53(2):180-195. doi:10.1093/abm/kay026
41. Taylor GMJ, Dalili MN, SemwalM, Civljak M, Sheikh A, Car J. Internet-based interventions for smoking cessation. Cochrane Database Syst Rev. 2017;9(9):CD007078.
42. Graham AL, Carpenter KM, Cha S, et al. Systematic review and meta-analysis of internet interventions for smoking cessation among adults. Subst Abuse Rehabil. 2016;7:55-69. doi:10.2147/SAR.S101660
43. Notley C, Gentry S, Livingstone-Banks J, Bauld L, Perera R, Hartmann-Boyce J. Incentives for smoking cessation. Cochrane Database Syst Rev. 2019;7(7):CD004307.
44. Giles EL, Robalino S, McColl E, Sniehotta FF, Adams J. The effectiveness of financial incentives for health behaviour change: systematic review and meta-analysis. PLoS One. 2014;9(3):e90347. doi:10.1371/journal.pone.0090347
45. Clair C, Mueller Y, Livingstone-Banks J, et al. Biomedical risk assessment as an aid for smoking cessation. Cochrane Database Syst Rev. 2019;3(3):CD004705. doi:10.1002/14651858.CD004705.pub5
46. Ussher MH, Faulkner GEJ, Angus K, Hartmann-Boyce J, Taylor AH. Exercise interventions for smoking cessation. Cochrane Database Syst Rev. 2019;2019(10):CD002295.
47. Klinsophon T, Thaveeratitham P, Sitthipornvorakul E, Janwantanakul P. Effect of exercise type on smoking cessation: ameta-analysis of randomized controlled trials. BMC Res Notes. 2017;10(1):442. doi:10.1186/s13104-017-2762-y
48. White AR, Rampes H, Liu JP, Stead LF, Campbell J. Acupuncture and related interventions for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000009. doi:10.1002/14651858.CD000009.pub4
49. Barnes J, McRobbie H, Dong CY, Walker N, Hartmann-Boyce J. Hypnotherapy for smoking cessation. Cochrane Database Syst Rev. 2019;6:CD001008.
50. Boyle R, Solberg L, Fiore M. Use of electronic health records to support smoking cessation. Cochrane Database Syst Rev. 2014;(12):CD008743. doi:10.1002/14651858.CD008743.pub3
51. Thomas D, Abramson MJ, Bonevski B, George J. System change interventions for smoking cessation. Cochrane Database Syst Rev. 2017;2(2):CD010742.
52. Lindson N, Klemperer E, Hong B, Ordóñez-Mena JM, Aveyard P. Smoking reduction interventions for smoking cessation. Cochrane Database Syst Rev. 2019;9(9):CD013183.
53. Livingstone-Banks J, Norris E, Hartmann-Boyce J, West R, Jarvis M, Hajek P. Relapse prevention interventions for smoking cessation. Cochrane Database Syst Rev. 2019;2(2):CD003999.
54. Chamberlain C, O’Mara-Eves A, Porter J, et al. Psychosocial interventions for supporting women to stop smoking in pregnancy. Cochrane Database Syst Rev. 2017;2(2):CD001055. doi:10.1002/14651858.CD001055.pub5
55. Griffiths SE, Parsons J, Naughton F, Fulton EA, Tombor I, Brown KE. Are digital interventions for smoking cessation in pregnancy effective? a systematic review and meta-analysis. Health Psychol Rev. 2018;12(4):333-356. doi:10.1080/17437199.2018.1488602
56. Wilson SM, Newins AR, Medenblik AM, et al. Contingency management versus psychotherapy for prenatal smoking cessation: a meta-analysis of randomized controlled trials. Womens Health Issues. 2018;28(6):514-523. doi:10.1016/j.whi.2018.05.002
57. Wu L, Sun S, He Y, Zeng J. Effect of smoking reduction therapy on smoking cessation for smokers without an intention to quit: an updated systematic review and meta-analysis of randomized controlled. Int J Environ Res Public Health. 2015;12(9):10235-10253. doi:10.3390/ijerph120910235
58. Apollonio D, Philipps R, Bero L. Interventions for tobacco use cessation in people in treatment for or recovery from substance use disorders. Cochrane Database Syst Rev. 2016;11(11):CD010274. doi:10.1002/14651858.CD010274.pub2
59. Thurgood SL, McNeill A, Clark-Carter D, Brose LS. A systematic review of smoking cessation interventions for adults in substance abuse treatment or recovery. Nicotine Tob Res. 2016;18(5):993-1001. doi:10.1093/ntr/ntv127
60. Wilson A, Guillaumier A, George J, Denham A, Bonevski B. A systematic narrative review of the effectiveness of behavioural smoking cessation interventions in selected disadvantaged groups (2010-2017). Expert Rev Respir Med. 2017;11(8):617-630. doi:10.1080/17476348.2017.1340836
61. Boland VC, Stockings EA, Mattick RP, McRobbie H, Brown J, Courtney RJ. Themethodological quality and effectiveness of technology-based smoking cessation interventions for disadvantaged groups: a systematic review and meta-analysis. Nicotine Tob Res. 2018;20(3):276-285. doi:10.1093/ntr/ntw391
62. Liu JJ, Wabnitz C, Davidson E, et al. Smoking cessation interventions for ethnic minority groups—a systematic review of adapted interventions. Prev Med. 2013;57(6):765-775. doi:10.1016/j.ypmed.2013.09.014
63. Johnston V, Westphal DW, Glover M, Thomas DP, Segan C, Walker N. Reducing smoking among indigenous populations: new evidence from a review of trials. Nicotine Tob Res. 2013;15(8):1329-1338. doi:10.1093/ntr/ntt022
64. Carson KV, Brinn MP, Peters M, Veale A, Esterman AJ, Smith BJ. Interventions for smoking cessation in indigenous populations. Cochrane Database Syst Rev. 2012;1(1):CD009046. doi:10.1002/14651858.CD009046.pub2
65. Schuit E, Panagiotou OA, Munafò MR, Bennett DA, Bergen AW, David SP. Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers. Cochrane Database Syst Rev. 2017;9(9):CD011823. doi:10.1002/14651858.CD011823.pub2
66. Khanna P, Clifton AV, Banks D, Tosh GE. Smoking cessation advice for people with serious mental illness. Cochrane Database Syst Rev. 2016;1(1):CD009704. doi:10.1002/14651858.CD009704.pub2
67. Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev. 2013;(2):CD007253. doi:10.1002/14651858.CD007253.pub3
68. van der Meer RM, Willemsen MC, Smit F, Cuijpers P. Smoking cessation interventions for smokers with current or past depression. Cochrane Database Syst Rev. 2013;(8):CD006102. doi:10.1002/14651858.CD006102.pub2
69. Peckham E, Brabyn S, Cook L, Tew G, Gilbody S. Smoking cessation in severe mental ill health: what works? an updated systematic review and meta-analysis. BMC Psychiatry. 2017;17(1):252. doi:10.1186/s12888-017-1419-7
70. Roberts E, Eden Evins A, McNeill A, Robson D. Efficacy and tolerability of pharmacotherapy for smoking cessation in adults with serious mental illness: a systematic review and network meta-analysis. Addiction. 2016;111(4):599-612. doi:10.1111/add.13236
71. Ahmed S, Virani S, Kotapati VP, et al. Efficacy and safety of varenicline for smoking cessation in schizophrenia: a meta-analysis. Front Psychiatry. 2018;9:428. doi:10.3389/fpsyt.2018.00428
72. Kishi T, Iwata N. Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2015;265(3):259-268. doi:10.1007/s00406-014-0551-3
73. Wu Q, Gilbody S, Peckham E, Brabyn S, Parrott S. Varenicline for smoking cessation and reduction in people with severe mental illnesses: systematic review and meta-analysis. Addiction. 2016;111(9):1554-1567. doi:10.1111/add.13415
74. Smith PH, Weinberger AH, Zhang J, Emme E, Mazure CM, McKee SA. Sex differences in smoking cessation pharmacotherapy comparative efficacy: a network meta-analysis. Nicotine Tob Res. 2017;19(3):273-281.
75. McKee SA, Smith PH, Kaufman M, Mazure CM, Weinberger AH. Sex differences in varenicline efficacy for smoking cessation: ameta-analysis. Nicotine Tob Res. 2016;18(5):1002-1011. doi:10.1093/ntr/ntv207
76. Ebbert JO, Elrashidi MY, Stead LF. Interventions for smokeless tobacco use cessation. Cochrane Database Syst Rev. 2015;(10):CD004306.
77. Schwartz J, Fadahunsi O, Hingorani R, et al. Use of varenicline in smokeless tobacco cessation: a systematic review and meta-analysis. Nicotine Tob Res. 2016;18(1):10-16.
78. Whittaker R, McRobbie H, Bullen C, Rodgers A, Gu Y. Mobile phone-based interventions for smoking cessation. Cochrane Database Syst Rev. 2016;4:CD006611.
79. Bullen C, Williman J, Howe C, et al. Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation. BMC Public Health. 2013;13:210. doi:10.1186/1471-2458-13-210
80. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637. doi:10.1016/S0140-6736(13)61842-5
81. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013;8(6):e66317. doi:10.1371/journal.pone.0066317
82. Masiero M, Lucchiari C, Mazzocco K, et al. E-cigarettes may support smokers with high smoking-related risk awareness to stop smoking in the short run: preliminary results by randomized controlled trial. Nicotine Tob Res. 2019;21(1):119-126. doi:10.1093/ntr/nty047
83. Carpenter MJ, Heckman BW,Wahlquist AE, et al. A naturalistic, randomized pilot trial of e-cigarettes: uptake, exposure, and behavioral effects. Cancer Epidemiol Biomarkers Prev. 2017;26(12):1795-1803. doi:10.1158/1055-9965.EPI-17-0460
84. Cravo AS, Bush J, Sharma G, et al. A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks. Regul Toxicol Pharmacol. 2016;81(suppl 1):S1-S14. doi:10.1016/j.yrtph.2016.10.003
85. Lucchiari C, Masiero M, Veronesi G, et al. Benefits of e-cigarettes among heavy smokers undergoing a lung cancer screening program: randomized controlled trial protocol. JMIR Res Protoc. 2016;5(1):e21. doi:10.2196/resprot.4805
86. Tseng TY, Ostroff JS, Campo A, et al. A randomized trial comparing the effect of nicotine versus placebo electronic cigarettes on smoking reduction among young adult smokers. Nicotine Tob Res. 2016;18(10):1937-1943. doi:10.1093/ntr/ntw017
87. O’Brien B, Knight-West O,Walker N, Parag V, Bullen C. E-cigarettes versus NRT for smoking reduction or cessation in people with mental illness: secondary analysis of data from the ASCEND trial. Tob Induc Dis. 2015;13(1):5. doi:10.1186/s12971-015- 0030-2
88. Bullen C, Howe C, Laugesen M. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637. doi:10.1016/S0140-6736(13)61842-5
89. Caponnetto P, Campagna D, Cibella F, et al. Correction: EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. Published 2014. doi:10.1371/annotation/e12c22d3-a42b-455d-9100-6c7ee45d58d0
90. Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629-637. doi:10.1056/NEJMoa1808779
91. Walker N, Parag V, Verbiest M, Laking G, Laugesen M, Bullen C. Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. Lancet Respir Med. 2020;8(1):54- 64. doi:10.1016/S2213-2600(19)30269-3
92. Hajek P, Phillips-Waller A, Przulj D, et al. E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT. Health Technol Assess. 2019;23(43):1-82. doi:10.3310/hta23430
93. Lee SH, Ahn SH, Cheong YS. Effect of electronic cigarettes on smoking reduction and cessation in Korean male smokers: a randomized controlled study. J Am Board Fam Med. 2019;32(4):567-574. doi:10.3122/jabfm.2019.04.180384
94. Masiero M, Lucchiari C, Mazzocco K, et al. Corrigendum: e-cigarettes may support smokers with high smoking-related risk awareness to stop smoking in the short run: preliminary results by randomized controlled trial. Nicotine Tob Res. 2020;22(4):594-595. doi:10.1093/ntr/nty175
95. Rose G, Hamilton PJ. A randomised controlled trial of the effect on middle-aged men of advice to stop smoking. J Epidemiol Community Health (1978). 1978;32(4):275-281. doi:10.1136/jech.32.4.275
96. Rose G, Colwell L. Randomised controlled trial of anti-smoking advice: final (20 year) results. J Epidemiol Community Health. 1992;46(1):75-77. doi:10.1136/jech.46.1.75
97. Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031.
98. Berlin I, Grangé G, Jacob N, Tanguy ML. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. BMJ. 2014;348:g1622. doi:10.1136/bmj.g1622
99. Coleman T, Cooper S, Thornton JG, et al; Smoking, Nicotine, and Pregnancy (SNAP) Trial Team. A randomized trial of nicotine-replacement therapy patches in pregnancy. N Engl J Med. 2012;366(9):808-818. doi:10.1056/NEJMoa1109582
100. Cooper S, Lewis S, Thornton JG, et al; Smoking, Nicotine and Pregnancy Trial Team. The SNAP trial: a randomised placebo-controlled trial of nicotine replacement therapy in pregnancy—clinical effectiveness and safety until 2 years after delivery, with economic evaluation. Health Technol Assess. 2014;18(54):1-128. doi:10.3310/hta18540
101. Cooper S, Taggar J, Lewis S, et al; Smoking, Nicotine and Pregnancy (SNAP) Trial Team. Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial. Lancet Respir Med. 2014;2(9):728-737. doi:10.1016/S2213-2600(14)70157-2
102. El-Mohandes AA, Windsor R, Tan S, Perry DC, Gantz MG, Kiely M. A randomized clinical trial of trans-dermal nicotine replacement in pregnant African-American smokers. Matern Child Health J. 2013;17(5):897-906. doi:10.1007/s10995-012-1069-9
103. Essex HN, Parrott S, Wu Q, Li J, Cooper S, Coleman T. Cost-effectiveness of nicotine patches for smoking cessation in pregnancy: a placebo randomized controlled trial (SNAP). Nicotine Tob Res. 2015;17(6):636-642. doi:10.1093/ntr/ntu258
104. Iyen B, Vaz LR, Taggar J, Cooper S, Lewis S, Coleman T. Is the apparently protective effect of maternal nicotine replacement therapy (NRT) used in pregnancy on infant development explained by smoking cessation? secondary analyses of a randomised controlled trial. BMJ Open. 2019;9(7):e024923. doi:10.1136/bmjopen-2018-024923
105. Oncken C, Dornelas E, Greene J, et al. Nicotine gum for pregnant smokers: a randomized controlled trial. Obstet Gynecol. 2008;112(4):859-867. doi:10.1097/AOG.0b013e318187e1ec
106. Oncken C, Dornelas EA, Kuo C-L, et al. Randomized trial of nicotine inhaler for pregnant smokers. Am J Obstet Gynecol MFM. 2019;1(1):10-18. doi:10.1016/j.ajogmf.2019.03.006
107. Pollak KI, Oncken CA, Lipkus IM, et al. Nicotine replacement and behavioral therapy for smoking cessation in pregnancy. Am J Prev Med. 2007;33(4): 297-305. doi:10.1016/j.amepre.2007.05.006
108. Vaz LR, Coleman T, Cooper S, Aveyard P, Leonardi-Bee J; SNAP Trial Team. The nicotine metabolite ratio in pregnancy measured by trans-3'-hydroxycotinine to cotinine ratio: characteristics and relationship with smoking cessation. Nicotine Tob Res. 2015;17(11):1318-1323. doi:10.1093/ntr/ntu342
109. Wisborg K, Henriksen TB, Jespersen LB, Secher NJ. Nicotine patches for pregnant smokers: a randomized controlled study. Obstet Gynecol. 2000;96(6):967-971. doi:10.1097/00006250-200012000-00019
110. Bérard A, Zhao JP, Sheehy O. Success of smoking cessation interventions during pregnancy. Am J Obstet Gynecol. 2016;215(5):611.e1-611.e8. doi:10.1016/j.ajog.2016.06.059
111. Dhalwani NN, Szatkowski L, Coleman T, Fiaschi L, Tata LJ. Nicotine replacement therapy in pregnancy and major congenital anomalies in offspring. Pediatrics. 2015;135(5):859-867. doi:10.1542/peds.2014-2560
112. Dhalwani NN, Szatkowski L, Coleman T, Fiaschi L, Tata LJ. Stillbirth among women prescribed nicotine replacement therapy in pregnancy: analysis of a large UK pregnancy cohort. Nicotine Tob Res. 2019;21(4):409-415. doi:10.1093/ntr/nty019
113. Pedersen L, Petronis KR, Nørgaard M, et al. Risk of adverse birth outcomes after maternal varenicline use: a population-based observational study in Denmark and Sweden. Pharmacoepidemiol Drug Saf. 2020;29(1):94-102. doi:10.1002/pds.4894
114. Tran DT, Preen DB, Einarsdottir K, et al. Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. BMC Med. 2020;18(1):15. doi:10.1186/s12916-019-1472-9
115. Zhu JL, Olsen J, Liew Z, Li J, Niclasen J, Obel C. Parental smoking during pregnancy and ADHD in children: the Danish national birth cohort. Pediatrics. 2014;134(2):e382-e388. doi:10.1542/peds.2014-0213
116. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387(10037):2507-2520. doi:10.1016/S0140-6736(16)30272-0
117. Claire R, Chamberlain C, Davey MA, et al. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2020;3:CD010078. doi:10.1002/14651858.CD010078.pub3
118. Krishnasamy VP, Hallowell BD, Ko JY, et al; Lung Injury Response Epidemiology/Surveillance Task Force. Update: characteristics of a nationwide outbreak of e-cigarette, or vaping, product use–associated lung injury—United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020;69(3):90-94. doi:10.15585/mmwr.mm6903e2
119. National Academies of Sciences, Engineering, and Medicine. Public Health Consequences of E-Cigarettes. National Academies Press; 2018.
120. Wang TW, Asman K, Gentzke AS, et al. Tobacco product use among adults—United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67(44):1225-1232. doi:10.15585/mmwr.mm6744a2

Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. A dashed line indicates a health outcome that immediately follows an intermediate outcome. Additional Information available in the USPSTF Procedure Manual.⁷

Abbreviations: KQ, key question; NRT, nicotine replacement therapy; SMI, severe mental illness.
^a Primary reviews are those that represented the most current evidence, most applicable evidence, or both within each population and intervention subgroup and served as the basis for the main findings of this report.
^b Review credibility assessed using AMSTAR-2 (Assessment of Multiple Systemic Reviews 2).^9
c Included in previous US Preventive Services Task Force review; has not been updated.

Abbreviations: EHR, electronic health record; NA, not applicable; NRT, nicotine replacement therapy; RCT, randomized clinical trial; RR, risk ratio.
^a Used strictest available criterion to define abstinence (ie, continuous, sustained, or prolonged abstinence was preferred over point prevalence abstinence, and biochemically validated rates were used when available).
^b Each review pooled data from the longest follow-up point reported at 6 or more months of follow-up.
^c Weighted average quit rates.
^d Includes 3 RCTs and 4 quasi-experimental studies.
^e No meta-analysis performed. Six studies reported the effects of the intervention on smoking cessation. Only 1 study reported a statistically significant benefit of the use of a decision aid vs usual care on smoking cessation at 6 months.
^f Irrespective of level of contact and support common to control group.
^g Includes 7 RCTs and 9 nonrandomized observational studies.
^h In general, this review found no evidence of a difference in smoking cessation at 6 months’ or greater follow-up among trials that compared hypnotherapy vs no intervention or other smoking cessation interventions. In the group with the most trials, there was no overall difference in smoking cessation rates between groups at 6 months or greater follow-up between hypnotherapy vs attention-matched smoking cessation behavioral intervention (RR, 1.21 [95% CI, 0.91-1.61]; 6 studies; n = 957; I² = 36%).
ⁱ Only 1 RCT (n = 9589) reported effects on smoking cessation, as captured in the EHR, and found that more intervention vs control clinic smokers quit (5.3% vs 1.9%, P < .001). The remaining studies focused on the impact of EHR changes on smoking support actions by clinicians, clinics, and health systems, with most studies reporting improved processes following EHR-facilitated intervention implementation.
^j Four trials (n = 7142) reported the effects of the intervention on smoking cessation, finding mixed results. Across all 7 trials, there was mixed evidence on secondary process outcomes such as documentation of smoking status and provision of counseling.

Abbreviations: e-cigarette, electronic cigarette; NA, not applicable; NRT, nicotine replacement therapy; OR, odds ratio; RCT, randomized clinical trial; RR, risk ratio.
^a Number of included studies reflects the number of systematic reviews designated as primary evidence for that body of evidence as well as the summed total number of included studies and observations from each review.
^b For the review-of-reviews method, the strength of the overall body of evidence assigned within the primary systematic review was adopted. In most cases, these grades were based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group definitions, which consider study limitations, consistency of effect, imprecision, indirectness, and publication bias. Where strength of evidence grades were not available, the Evidence-based Practice Center approach was adapted to assign an overall strength of evidence grade based on consensus discussions involving at least 2 reviewers.^10
c Some evidence of asymmetry in a funnel plot; excess of small trials detecting larger effects. However, in a sensitivity analysis, removing smaller studies did not markedly decrease the pooled estimate.
^d Sensitivity analysis including only those studies judged to have a low risk of bias did not affect the pooled results for any comparison; for NRT and bupropion, the funnel plots showed some evidence of asymmetry. However, given the large number of trials in these reviews, this does not suggest the results would be altered significantly were smaller studies with lower RRs included.
^e Evidence from existing systematic reviews as well as the EAGLES trial indicate that adult smokers randomized to varenicline have a statistically significant higher likelihood of quitting smoking at 6 months compared with those randomized to NRT or bupropion. In the EAGLES trial (n = 8144) 21.8% of smokers randomized to varenicline quit smoking at 6 months compared with 15.7% randomized to NRT (odds ratio, 1.52 [95% 1.29-1.78]) and 16.2% randomized to bupropion (odds ratio, 1.45 [95% CI, 1.24-1.70]).^116
f Quality of the evidence differs for each specific type of intervention but generally reflects moderate to high certainty grades. Most common reasons for downgraded the quality of evidence were unexplained statistical heterogeneity, several studies with high or unclear risk of bias, or inconsistency in the evidence base.
^g Total number of studies and observations not estimated.
^h Despite the relatively limited number of reviews that reported harms related to interventions, it appears likely that there are no serious harms related to combined pharmacotherapy and behavioral counseling interventions or behavioral counseling alone for tobacco cessation.