Urgent Need for Novel Investigations of Treatments to Quit E-cigarettes: Findings from a Systematic Review

Cigarette smoking is a well-known contributor to disease and mortality, including cancer (1); thus, smoking prevention and cessation efforts are critical components of cancer control. Recently, adults (2) and youth (3) have reported use of electronic (e-cigarettes), often as an aid in smoking cessation. E-cigarettes are battery powered devices that heat a liquid nicotine solution to the point of aerosolization. These products were first developed and introduced into international markets in the late 2000s and have since become more advanced in technology and efficient in nicotine delivery.

Smoking rates in the United States have been steadily declining over the past few decades. The slope of the decline in smoking has been somewhat stronger since the advent of e-cigarettes to the U.S. market, with current smoking prevalence estimated to be 12.5% (2, 4). E-cigarette use prevalence initially rose quickly and has since leveled out with adult use estimates between 3.7% and 4.5% (2, 5). While adult prevalence has remained stable, reports of adolescent and young adult (youth) e-cigarette use (also referred to as vaping) is rising, which is an alarming trend considering many have never used other tobacco. E-cigarettes have surpassed combustible cigarettes as the most common nicotine-containing product used by youth (6), with 11.3% of high school students and 2.8% of middle school endorsing past 30-day use (3). There is concern that youth who use e-cigarettes may be at higher risk for cigarette smoking in the future due to changing social norms, gateway effects, and neurobiological changes in vulnerability to substance use resulting from nicotine exposure (7). For these reasons, tobacco control efforts in the U.S. have shifted a great deal of effort to the prevention of e-cigarette initiation among youth as well as developing methods to intervene on vaping behaviors.

An assessment of trends from 2014 to 2018 suggests increases over time in the prevalence among young adults without a smoking history and middle/older age adults who used e-cigarettes to quit smoking (8). Overall, most e-cigarette users are individuals with a current or past cigarette smoking history, although the gap between prevalence rates of those with and without a cigarette smoking history is narrowing. In fact, recent evidence from the U.S. FDA Population Assessment of Tobacco and Health (PATH) survey revealed that e-cigarette users who have never smoked show the most past year e-cigarette quit attempts (9).

The tobacco research community has been increasingly accepting of adopting a harm reduction framework, wherein tobacco/nicotine products are considered on a spectrum of risk from combustible cigarettes as most harmful to pharmaceutical nicotine replacement therapy (NRT) as least harmful and e-cigarettes somewhere in between (10, 11). Indeed, accumulated evidence from clinical trials show promise for the clinical utility and safety of e-cigarettes for smoking cessation (12). However, these trials all share an interesting outcome: Among the individuals who were able to switch from combustible cigarettes to e-cigarettes, a majority continue to vape following the conclusion of the intervention period. For instance, one smoking cessation trial testing e-cigarettes plus nicotine replacement therapy found that about 58% of participants continued to use e-cigarettes 6 months after treatment. Another study testing e-cigarettes for smoking cessation found that 80% continued to vape 12 months after treatment (13). Interestingly, high continued uptake post smoking cessation is not generally observed with traditional tobacco pharmacotherapy (e.g., the nicotine patch). This phenomenon suggests that those who quit smoking with e-cigarettes may be reliant on e-cigarettes to maintain their smoking abstinence (14) or may face challenges when trying to stop e-cigarette use. Whereas abstinence from smoking should be encouraged, some individuals who vape may experience functional impairments due to their dependence.

Based on recent national survey data from the U.S. FDA PATH study, both youth and adults demonstrate interest in quitting e-cigarettes (9, 15, 16). Despite substantial reported desire for cessation, however, there is limited empirical evidence on how to support those who vape in their quit attempts. The purpose of this article is to provide a systematic review of the current literature with human subjects, including a variety of study designs exploring interest, prevalence, and interventions for e-cigarette cessation. Data from qualitative and survey sources that contribute to the theoretical understanding of the process of vaping cessation are reviewed, in addition to evidence from clinical trials and other intervention studies for e-cigarette cessation, which can provide preliminary evidence on the effectiveness of existing treatments. Studies are inclusive of a broad spectrum of age groups (youth and adults who vape) as these groups all have specific needs related to vaping cessation. To conclude the review, a research agenda is provided, including recommendations within the domain of vaping cessation based on the theoretical findings reviewed as well as results from intervention trials. This agenda can serve as a guide for clinicians and researchers to inform future treatment development and implementation decisions.

A systematic review of literature was conducted with the cessation of e-cigarettes as the primary domain of interest. Studies that captured data on reducing e-cigarette use were also included. This review protocol was publicly registered on PROSPERO (CRD42021242508; ref. 17).

Given a cursory review of available literature, which showed limited published clinical trials within this domain, eligibility for review included a range of study types: (i) qualitative studies utilizing any data collection method (e.g., focus groups, individual interviews) that was thematically analyzed; (ii) quantitative studies collecting longitudinal, cross-sectional, and/or cohort data (i.e., surveys); and (iii) any published data on interventions, inclusive of randomized controlled trials (RCT), quasi-RCTs, prospective cohort studies, before-and-after studies (e.g., ABAB behavioral designs), and case studies.

This is a budding area of research, so limited literature was expected. Given the novelty of the outcomes and critical need for this review, we endeavored to be as inclusive as possible for studies and included investigations with or without control or comparison groups. The primary goal is to summarize the extant e-cigarette cessation literature, including attitudes toward and epidemiologic rates of e-cigarette cessation and reduction, as data regarding the efficacy and effectiveness of interventions may be limited.

Studies were limited to human subjects research. The review was not limited by age, geographic location, or inclusion of data related to the use of other tobacco products (if the outcome was specifically e-cigarette cessation). Individuals who currently use e-cigarettes or had a former history of regular e-cigarette use were included. Operational definitions of current and former use were allowed to be determined by the authors of each reviewed publication and were documented for comparison across studies. E-cigarettes were defined as battery-powered devices that contain a heating coil and liquid solution containing propylene glycol, vegetable glycerin, nicotine, and usually flavoring (18). More contemporary devices, such as pod mods, instead utilize a protonated nicotine (“nicotine salts”) solution within a smaller, sleeker device (19) and may have been mentioned by brand name in the studies (e.g., JUUL). Studies examining vaping of substances other than nicotine (e.g., marijuana) were excluded. We included studies of individuals who vape and might be using tobacco products concurrently, such as cigarettes (i.e., “dual users”).

Outcomes captured include the following: (i) E-cigarette cessation at any point, by any measure including self-report; (ii) E-cigarette reduction at any point, by any measure including self-report; (iii) making a past quit attempt or attempt to reduce e-cigarette use; (iv) intentions or plans to quit or reduce e-cigarette use behaviors; (v) intervention methodology, study engagement, and study retention. We excluded studies on barriers and facilitators to e-cigarette cessation, as a review of this topic already exists (20). Outcomes reporting changes in e-cigarette use prevalence trends that were not explicitly indicative of intentional changing were excluded, as were general tobacco use outcomes (e.g., “quit tobacco”) when assessing products beyond cigarettes and e-cigarettes.

The following databases were searched: PubMed, MEDLINE, Scopus, PsycINFO, and ProQuest Dissertation and Theses Database. The search was limited to articles published after 2010, given the advent of mainstream emergence of e-cigarettes in the tobacco marketplace, and the search concluded with articles published in September 2021. Literature searches were conducted from April 2021 to September 2021. Search terms used included the following: “electronic cigarette cessation,” “electronic cigarette quit,” “electronic nicotine delivery system cessation,” “electronic nicotine delivery system quit,” in titles and abstracts. Any included studies that were reviews were cross-referenced for additional references to screen. Searches were restricted to those published in English language.

References were imported into Covidence (Veritas Health Innovation), a platform designed to facilitate the extraction and assessment of references for systematic reviews. Duplicates were removed. Four authors served as abstract reviewers, and three conducted the data extraction and quality assessment.

Articles identified in the initial search were then independently screened by two coders who evaluated the title and abstract for inclusion in review. Upon completion, any discrepancies between ratings were resolved via a discussion between two coders. The full text of any article deemed to be potentially relevant for the included review were retrieved and evaluated for inclusion for review each by two coders.

The final reference list was distributed evenly amongst three coders for data extraction and quality assessment ratings. Reviewers pulled information regarding the type of study, study population, measures related to e-cigarette cessation, and outcomes from each study. The quality of the studies was rated using the Critical Appraisal Skills Programme (CASP) Checklists (21) for RCTs (maximum score = 13), Cohort Studies (maximum score = 14), Case Control Studies (maximum score = 10), and Qualitative studies (maximum score = 10), and the Center for Evidence Based Management (CEBMa) Critical Appraisal Checklist for Cross-Sectional Studies (maximum score = 12; ref. 22). Studies were rated on each item within the checklist, and an overall score was calculated by coding ratings and adding the sums: 1 = yes, 0.5 = somewhat/not sure, and 0 = no.

The final data extracted from articles included were sent for review to all authors. Following individual review, the authors met together to discuss findings for a priori themes as well as additional themes that emerged. To begin, we opted to seek out themes related to outcomes of interest, including motivation and intent to quit, quitting experiences, and methods for quitting. A priori, we believed that articles might be best thematically evaluated by age groups, as there are differences in rates and reasons for e-cigarette use among different aged populations. Another a priori aim was to evaluate the degree to which identified interventions and treatments were consistent with results from survey and qualitative literature regarding what e-cigarette users stated they desired in a treatment.

The data extracted and used in analysis are available within the article and its supplementary data files.

The PRISMA Flow Diagram reports records identified, duplicates, screened for inclusion, submitted to full-text evaluation, and those included in the final review (Fig. 1).

The review process yielded 79 studies meeting the inclusion criteria. A total of 56 studies utilized a cross sectional design (Supplementary Table S1). Of note, one study that appeared in search databases was an unpublished undergraduate thesis and was obtained via written permission from the primary mentor (Kelly Davis, PhD). Six studies utilized qualitative designs with focus groups, two additional mixed-methods studies used focus groups and surveys, five studies analyzed cohort data, and three used experimental manipulations with cross-sectional data (Supplementary Table S2).

Seven studies were identified as examining the outcome of an intervention or manipulation (Table 1), including 2 RCTs, 1 pilot intervention trial, 3 case studies, and 1 case series. One of the randomized controlled trials and two of the case studies implemented NRT as their primary intervention, whereas one case study reported the use of varenicline. One of the RCTs tested a fully automated text message–based intervention. Two of the case studies implemented behavioral support and motivational interventions or monitored tapering.

Most studies were with U.S. samples (63/79, 79.74%) and other countries included Australia, Belarus, Belgium, Canada, France, Jordan, Lithuania, Malaysia, the Netherlands, Poland, Russia, Slovakia, Switzerland, and United Kingdom (England). There were 25 cross-sectional studies of adolescents/young adults and 31 of general adults. Within the cross-sectional studies, participants were derived from representative national datasets (9, 15, 16, 23–34) and convenience samples, including online survey panels (35–54), school and college samples (34, 55–63), patient samples (64–68), vape shop customers (69, 70), and other sources (71–73). There were generally equal numbers of youth/adolescent and adult samples in cohort, experimental, and qualitative studies. Experimental studies recruited participants from online convenience samples (74–76). Cohort studies recruited participants from national databases (77–79), patient samples (80), and market research sources (81). Qualitative studies recruited patients from convenience samples (including school, college, online, and marketing sources; refs. 58, 82–86) and from other studies (87, 88). Case studies were generally of younger individuals, and the RCTs recruited adolescents/young adults. Case studies used convenience samples of patients (89–92), whereas RCTs recruited from the general community (93–95).

The most common outcomes measured in cross-sectional, cohort, experimental, and qualitative studies (some of which captured multiple outcomes) were interest in quitting (15/72, 20.8%), intent to quit (within varying timeframes; 29/72, 40.3%), and past quit attempts (lifetime or within a recent timeframe; 32/72, 44.4%), reasons/motivations for quitting (20/72, 27.8%), interest in treatments, and experience with quitting (9/72, 12.5%). Outcomes in case studies and RCTs were self-reported abstinence (7/7, 100%), except for one that also reported biochemically confirmed abstinence (1/7, 14.3%).

Quality of the cross-sectional studies varied considerably (range, 4.5–11). In general, qualitative studies had high quality (range, 8–8.5), as did cohort studies (range, 7.5–11). A majority of RCTs and case studies were of low to moderate quality (range, 3.5–12). Points were commonly lost for not having a powered, unbiased, representative sample, not accounting for confounding variables (e.g., cigarette smoking status), and not including appropriate randomization or control groups. Regarding additional sources of bias, it should be noted that a set of four (38, 40, 47, 49) and a pair (43, 44) of cross-sectional studies appeared to use the same convenience sample but did not identify as such. Two qualitative studies self-identified as either secondary analyses or using participants from previous research (87, 88).

Most surveys and qualitative studies of youth, adolescents, and young adults (ages 12–30), a majority of which were conducted in Western countries, reported moderate to high prevalence of eventual intention to quit (43%–85%; refs. 16, 39, 56, 72, 82, 85). Those who had higher dependence or were dual users tended to have lower interest in quitting (34, 55, 56, 62, 67, 96), whereas those who reported experimenting with e-cigarettes tended to endorse future intent to quit (71, 72, 82, 84). In studies where participants were asked about a more proximal time frame for quitting, rates of self-reported intent to quit were lower (∼25%–31%; refs. 34, 60, 61, 67, 96).

There was greater inconsistency among adult studies (age 18+) assessing motivation and intention to quit, most of which were also from Western countries. Some studies suggested that most adults (up to ∼77%) have intention to quit e-cigarettes in the future (9, 15, 28, 65, 69, 70, 80), whereas other studies reported lower prevalence (as low as ∼25%; refs. 36, 41, 88). This discrepancy may be attributable to the source of the samples: Studies of participants who engaged in online e-cigarette forums endorsed lower interest in quitting (36, 41, 48, 88). Some studies found no substantial differences in interest or motivation to quit between those with different cigarette smoking histories (28, 50), whereas others reported differences (9, 26, 27). Finally, in general, higher nicotine dependence was associated with higher intentions to quit e-cigarettes (15, 35, 38, 47).

Although no studies directly tested differences between youth and adults, results were mixed as to whether older or younger age was associated with higher intentions to quit e-cigarettes (31, 67, 78, 81, 97).

Among youth, adolescents, and young adults, perceived negative health risks, such as those associated with COVID-19, oral health, or lung injury, were frequently cited as motivating intention to quit (24, 33, 45, 64, 67, 82–84, 86, 87). Additionally, a common theme mentioned among adolescents and college students was a feeling of social disapproval from friends, family, and future employers that motivated interest in quitting (33, 39, 67, 82–86). Limited access to e-cigarettes (e.g., ability to purchase, cost, restrictions) was also cited as a motivation for changing e-cigarette use (29, 37, 54, 59, 71, 85). Some youth lost interest in e-cigarettes, which is suggestive of experimental use (33, 54, 71, 72, 82, 84, 86). Finally, exposure to messages related to the harms of e-cigarette use were also related to increased intent to quit (32, 45, 57, 64, 75).

Among adults, perceptions of harm were related to higher intent to quit in some studies (26, 33, 42, 43, 49, 69, 74, 76). However, other studies showed that during COVID-19 most adults did not significantly change their level of interest in quitting (25, 30, 33, 44, 66). For those with experience using cigarettes and e-cigarettes, some studies showed that lack of satisfaction from e-cigarettes prompted cessation (27, 33, 43, 97). Cost concerns were associated with increased interest and motivation to quit (27, 43, 46, 70). Psychological factors, such as anxiety and self-efficacy, were also implicated in motivating quit attempts (38, 40, 49, 50). Finally, there were mixed results about the role of outcome expectancies impacting motivation to quit (33, 38, 40, 41, 47).

Among youth, a small proportion (∼12–32.3%) reported having made a quit attempt in the past year (16, 33, 55, 60, 61, 96), although the prevalence was higher among some young adult-aged samples (43.9%–58.7%; refs. 33, 62, 82, 85). Some youth reported taking a “break” from e-cigarettes, either due to lack of access or to reset tolerance (33, 37, 83). Dual use was associated with fewer past quit attempts in some studies (29, 55). Some studies showed that higher perception of harm and dependence were associated with past quit attempts (56, 67, 83, 84, 87, 96).

Among adults, a broader but higher range of prevalence of past year quit attempts was observed (∼11%–83%; refs. 9, 15, 27, 43, 51, 65, 66, 77, 78). In some studies, higher dependence was associated with more past year quit attempts (15, 33, 35, 38, 47, 81). Few adults (11%–21%; refs. 25, 30, 44, 66) reported quit attempts due to COVID-19.

Many studies did not probe on the method used for quitting. Among surveys of youth, most participants reported quitting unassisted and without pharmacotherapy (i.e., “cold turkey”; refs. 33, 61, 83). Adults were also likely to endorse quitting “cold turkey” (23, 43); however, studies of dual users found that pharmacotherapy (NRT, varenicline) was often sought and used, and in some cases, successful (23, 53, 65, 88). Some adults also reported tapering down their nicotine content (43). Both youth and adult samples expressed interest in an online/smartphone application to aid with quitting (36, 39).

All case studies and intervention trials were conducted in the United States, and all but one (89) used samples of young adults (age 17–35). Nonpharmacologic interventions included contingency management (94), text message support (93), behavioral counseling (90–92, 95), and e-cigarette nicotine tapering (33, 90, 95). Pharmacologic interventions included NRT (91, 92, 95) and varenicline (89). The text message program had a large, fully powered sample size, whereas the other studies had Ns of 1 to 24 and therefore were unable to draw strong conclusions regarding the efficacy of the treatment interventions. The text message support program demonstrated significant effectiveness for self-reported vaping cessation. Other pilot and case studies also showed evidence for the feasibility and acceptability of implementing both the pharmacologic and nonpharmacologic interventions. Only the contingency management study utilized biochemical confirmation of abstinence (i.e., cotinine testing).

The studies included in the review captured a comprehensive overview of interest and intent to quit e-cigarettes, and some studies evaluated factors that contributed to motivation, interest in specific strategies, and effectiveness of cessation techniques. Youth appeared to have a consistently higher prevalence of expressing intent and interest in quitting, whereas greater variability was seen among adults, who were also more heterogeneous in terms of cigarette smoking history. Youth tended to be more motivated by health concerns than adults, as evidenced by higher rates of changing vaping patterns during the early COVID-19 pandemic (although this may be also attributable to lost accessibility). Many survey respondents reported using a “cold turkey” approach to quitting, but it is unclear how efficacious this strategy might be given that a majority of the sample were current e-cigarette users. Finally, there was only one rigorous clinical trial for vaping cessation, and it was limited in intervention approach and target demographic.

Given these findings, several gaps in the literature emerged. To begin, there were no direct comparisons between youth and adults; all conclusions drawn between the age groups are subjective and observational. Next, there was a great deal of inconsistency in how to address dual users in the studies, including varying operational definitions of dual use, not controlling for smoking status in analyses, and the degree to which the study measures were specifically tailored to dual use or each individual product. Along similar lines, very few studies specifically aimed to evaluate subgroups of samples to determine whether the principles assessed apply to these groups (e.g., racial/ethnic minoritized populations, LGBTQ+, those with comorbid health or psychologic conditions). Likewise, given the varying regulatory and cultural influences on e-cigarette use, more global studies are needed. In terms of the outcomes of the studies, there were limited findings regarding the reasons motivating intentions to quit and quit attempts, particularly among adults. Importantly, the results from many surveys (9, 15, 16, 28, 39, 56, 65, 69, 70, 72, 80, 82, 85) suggest that a significant proportion of youth and adults intend to quit vaping, and further research has suggested strategies they might use to quit. Yet, there is little to no evidence on effective e-cigarette cessation strategies. Again, this gap is especially salient for older adult populations, who were largely not included in the case studies and intervention trials. Finally, most studies did not probe further into the participants who were uninterested in quitting. These individuals may have fewer functional impairments and more positive reinforcement from vaping, which might maintain use. Conversely, others may have significant barriers and challenges to quitting that decrease motivation to quit.

E-cigarette use has been increasing in popularity over the past decade (2, 3), and use patterns of these products is rapidly shifting as new devices come into the market and regulatory policies and public health campaigns respond (4). Increasing surveillance and interest in those who use e-cigarettes has prompted researchers to evaluate interest in vaping cessation and reasons for quitting and develop cessation interventions. Data from this systematic review of e-cigarette cessation suggest that many e-cigarette users are interested in eventually quitting e-cigarette use. Motivation for quitting vaping may be driven by several factors, including concerns about future health risks, negative social perceptions and/or stigma, and negative physical and psychologic consequences that arise from dependence on e-cigarettes/nicotine. However, very few intervention trials of pharmacotherapy and behavioral support exist to help those who wish to quit.

In the popular media, much focus is on youth vaping prevention and cessation efforts, which is of course merited due to concerns regarding risks of continued vaping and potential for transitions to cigarettes (7). In response to these concerns, a limited number of published studies have shown promise in developing vaping cessation interventions targeted for younger age groups. In general, these intervention studies have utilized gradual reduction of e-cigarette use or text messaging (90, 93, 95); both of which are intervention components supported by qualitative studies assessing preferred cessation methods for youth. However, these interventions fail to address a theme salient to youth and young adults, which is the need for social support. Studies in the review showed that social support from nonvaping peers might be protective and important for promoting cessation and maintaining abstinence (39, 67, 82–86). Future research should consider the impact of friends, family, and being around others who vape as a barrier to quitting. It should also be noted that recent historical events, such as the COVID-19 pandemic, have provided a quasi-experimental context with which to examine the effects of risk of severe health consequences on vaping cessation motivations and behaviors. Many youths did indeed report a reduction of e-cigarette use during this time, especially if their access was limited and they believed that e-cigarettes were harmful (24, 37). However, for adults, COVID-19 did not motivate interest or quit attempts to the same degree (25, 30, 44, 66). Future interventions may capitalize on the proximal health consequences of vaping that are relevant for youth to encourage cessation. In addition, policies and messaging campaigns might increase intent to quit; but to reiterate, youth who then are encouraged to quit must have the necessary support and resources available to sustain abstinence.

Although this body of work is showing promise for promoting youth e-cigarette cessation, it neglects the equally important population of older adults (i.e., ≥30 years) who also endorse motivation to quit vaping. Given differences in physical, social, and affective manifestations of e-cigarette use and dependence, all of which influence motivations to quit, it can be assumed that this population may require different treatment strategies. Most adults (the majority of whom were still vaping when surveyed) reported using “cold turkey” as a strategy to quit, which may have limited effectiveness (23, 43, 88). However, this may also be a result of a significant proportion of study participants being former cigarette smokers. Perhaps these individuals tried other pharmacotherapy to quit smoking and were unsuccessful until they transitioned to e-cigarettes. These negative medication expectancies may contribute to hesitation for pharmacotherapy to transition away from e-cigarettes. In addition, the dearth of evidence showing that pharmacotherapies work to quit e-cigarette use and the fact that health care providers have limited guidance for treatment decisions may have contributed to the lack of medication use. To date, no published trials have focused on developing vaping cessation interventions for adults of all ages. One study prospectively analyzed cessation outcomes among dual users of cigarettes and e-cigarettes and found that those who elected to use varenicline were more likely to quit (80). In addition, one case study showed evidence for varenicline for vaping cessation (89). These results suggest that adults, particularly those who have experience with cigarette smoking, may benefit from varenicline when attempting to quit vaping. Larger and more comprehensive studies in this regard are warranted.

Among both youth and adults, dependence was often related to interest in quitting and more past quit attempts, although results were mixed in terms of direction. It may be that for some, high nicotine dependence (as evidenced by self-report dependence measures and/or dual use of cigarette smoking) may represent an individual who has a greater challenge with cessation. On the other hand, those with high dependence may also experience more functional limitations and negative outcomes from their e-cigarette use, resulting in a desire for cessation. The role of physical and psychologic manifestations of nicotine dependence in promoting e-cigarette cessation should continue to be explored.

There are several limitations to the studies reviewed as well as the review itself. To begin, the quality ratings of the studies varied substantially. Among cross-sectional studies, sample sizes were sometimes underpowered or there was bias in the recruitment of the sample. In addition, confounding variables were often not accounted for, which is especially relevant for cigarette smoking status when drawing conclusions about interest in e-cigarette cessation. This being stated, although we attempted to have a narrow definition of the outcome of vaping cessation, through this review we encountered nuance within this definition. For instance, youth who experiment with e-cigarettes in certain contexts and then stop using when they do not have access may be described as having quit e-cigarettes, although the quit was not intentional per se. Adults who tried e-cigarettes as a means for smoking cessation but stopped because they were not satisfied with them may also be described as having quit e-cigarettes, although the instance of e-cigarette cessation is framed better as a discontinuation of use due to a lack of therapeutic response. These two nuanced situations were not formally parsed from intentional, motivated quit attempts, and therefore results should be interpreted with caution. Along similar lines, there was also variability in the measurement of outcomes. For instance, intent to quit may have been measured using a variety of phrasings, response options, and interpretations of variables. Therefore, our results may be biased toward our interpretations of the measurement of the constructs of interest. Future research should develop and utilize standardized measures for important outcomes to increase consistency between studies. Within the intervention studies, there were similar limitations in that the sample sizes were generally small, and the interventions studies were largely case reports and pilot trials, which limits the interpretability of the outcomes. Finally, most of the articles (61/77, 79.2%) were from U.S. samples, which limits the global generalizability and limited comparison between the United States and countries with different tobacco regulatory environments.

Limitations of the review strategy included articles published in English and available within the searched databases, which may somewhat account for the lack of international studies obtained for review. Our search terms included “cessation” and “quit” but did not include “reduction,” which may have missed studies with a focus on e-cigarette reduction specifically. In addition, we only included studies that explicitly evaluated e-cigarette cessation as an outcome, and therefore excluded studies investigating closely-related, relevant constructs (e.g., barriers to e-cigarette cessation; although a review for this already exists; ref. 20). Finally, we limited our search strategy to human subjects research, which excluded studies of other potentially relevant data (e.g., online postings).

A thorough, systematic review of the literature showed that a significant proportion of e-cigarette users are interested in quitting or have attempted to quit in the past. Reasons for wanting to quit are moderately understood, and less is known about the type of support or resources that would be acceptable and effective for this population. Given this scarcity of evidence on best practices and recommendations for e-cigarette cessation, we call for researchers to address the following important gaps in the extant literature:

1) Research should prioritize development and testing of e-cigarette treatment interventions, including both behavioral and pharmacologic approaches. These studies should address the concerns that are relevant for a broad range of ages. Older adults may have higher rates of concurrent cigarette smoking and health problems contraindicated for nicotine use. Interventions developed for youth and young adults are unlikely to generalize, given differences in tobacco use histories and motivations to quit. For this reason, a priority should be placed on older adults (i.e., >30 years) who are interested in e-cigarette cessation interventions, given that there is a complete lack of resources for this group. E-cigarette cessation interventions should theoretically align with empirically based practices to treat tobacco dependence, which recommends pharmacotherapy alongside behavioral interventions to maximize efficacy. Studies should include rigorous methodology (e.g., control groups, fully powered studies) to evaluate the effectiveness of behavioral treatments and pharmacotherapy. Behavioral interventions should draw from the reviewed literature to address themes that motivate users to make the decision to quit. Biochemical verification standards for e-cigarette abstinence have not been well established (98), so future research is encouraged to include multiple measures of abstinence in order to support the development of standard procedures. The use of smartphone applications was suggested by participants in studies, and this modality may be an effective means by which to create and disseminate interventions rapidly.

2) Research should focus on understanding dual users of cigarettes or other tobacco products. Studies should continue to parse the types of unique trajectories that users of tobacco products and e-cigarettes have, as the type of trajectory is relevant to the outcome of nicotine abstinence. Dual use of cigarettes and other tobacco should be accounted for in analyses, with a discussion of the appropriate limitations. Any combustible tobacco should be discouraged, given its association with numerous health conditions and cancers. Given these unique pathways of tobacco use patterns, the nuances of cessation outcome definitions must be considered. Finally, studies of poly-tobacco use trajectories should determine what might be the most effective pathway to abstinence. For instance, should dual users quit both products entirely at once, or should they transition from a harmful (combustible) to less harmful products (noncombustible; i.e., complete switching), after which they then achieve abstinence from the less harmful product? For whom might each strategy work better?

3) Research should draw upon empirically supported tobacco treatment interventions and apply them to e-cigarette cessation. Given the overlap in product use characteristics (e.g., nicotine, inhalation, seeing smoke/vapor, sensorimotor stimuli, flavors, brand loyalty, etc.), future studies could evaluate the extent to which strategies for smoking cessation apply to e-cigarettes. For example, recommendations for those who smoke might include using a sensorimotor distractor (e.g., straw) and switching brands of cigarettes. Could those who vape also benefit from those strategies? On the other hand, there are differences in use patterns between the products that are more distinct (e.g., vaping continuously all day as compared to individual cigarette smoking sessions), and thus, interventions may benefit from specific tailoring. Studies could recruit participants who have been successful in quitting tobacco products and probe, retrospectively, about what strategies were most useful and should be applied to future intervention research. Novel strategies, such as nicotine tapering, should be explored given the technology that allows for modifications to be made.

4) Future research should seek to understand more about e-cigarette users who are not interested in quitting. This includes sociodemographic differences in those who wish to quit compared with those who do not, as well as characteristics that may be maintaining use such as vaping enthusiasm, social acceptance, and clinical utility (i.e., former smokers who are using e-cigarettes to stay away from smoking). Importantly, those who have lost motivation to quit due to barriers and challenges to quitting should be a primary focus, as these individuals might gain motivation with such barriers removed. Studies should also aim to monitor long-term users with no desire to quit to assess for any potential negative consequences, or lack thereof.

As e-cigarette use and accessibility has evolved over time, a variety of populations have begun to use these products for different reasons. A systematic review of literature reporting e-cigarette cessation outcomes found 79 studies of mixed quality and results. Overall, studies showed that there was generally interest in e-cigarette cessation, and factors such as other tobacco use history, dependence, actual and perceived health effects, and social perceptions might impact interest in quitting. Many attempt to quit “cold turkey” but are unsuccessful. There are few evidence-based interventions for e-cigarette cessation available, representing a critical gap in clinical medicine. Future researchers should seek to fill this gap and investigate e-cigarette treatments to support the public health goal of reducing harm from tobacco.

L.M. Fucito reports other support from Imbrium Therapeutics outside the submitted work. B.A. Toll reports other support from expert testimony outside the submitted work. No disclosures were reported by the other authors.

This study has been funded by NIH Institutional Postdoctoral Training Grant NIH-T32-HL144470 (to A.M. Palmer and B.T. Sanford), the MUSC Hollings Cancer Center P30 CA138313 (to A.M. Palmer, S.N. Price, M.G. Foster, B.T. Sanford, and B.A. Toll), and the NIH and FDA Center for Tobacco Products (CTP) U54DA036151 (to L. Fucito). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.