The Role of Electronic Cigarettes for Tobacco Dependence Treatment

November 20, 2013

Stopping smoking affects the metabolism of a number of drugs used in the management of mental illness. Here, a summary of the author's published study on whether e-cigarettes with nicotine were more effective for smoking cessation than nicotine patches.

Electronic cigarettes (e-cigarettes) are a diverse and rapidly evolving range of battery-operated devices that vaporize nicotine for inhalation. Millions of people have purchased them.1 Indeed, e-cigarette sales are increasing so rapidly some analysts predict that they will overtake cigarette sales within a decade.2

Despite this mass use of a novel inhalable product, there is a remarkable paucity of reliable efficacy and safety data to inform debate over their place in treating tobacco dependence.3,4 Surveys show many smokers try e-cigarettes to cut down tobacco use or quit smoking,5,6 and studies show they are capable of attenuating tobacco withdrawal just as effectively as nicotine replacement therapy (NRT).7,8 Part of their appeal may be their simulation of the behavioral and sensory dimensions of smoking. But e-cigarette use could lead to harm: toxins have been found in e-cigarette fluid and vapor.9,10 However, the levels are similar to those found in NRT and are far lower than those in cigarette smoke.11 Indeed, a recent review deemed e-cigarettes to be very unlikely to pose significant risks to smokers.12[[{"type":"media","view_mode":"media_crop","fid":"21114","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_6049423444407","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1403","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image"}}]]

My colleagues and I conducted a pragmatic, randomized, controlled superiority trial in Auckland, New Zealand, between September 2011 and July 2013 to assess whether e-cigarettes with nicotine were more effective for smoking cessation than nicotine patches.13 We included a blind comparison with “placebo” e-cigarettes (containing no nicotine). We hypothesized that nicotine e-cigarettes would be more effective than patches and placebo e-cigarettes for smoking reduction, tobacco dependence, and relief of withdrawal symptoms, and that they would have no greater risk of adverse events than nicotine patches.

Smokers aged 18 years and older who wanted to quit were randomized to 16-mg nicotine e-cigarettes, nicotine patches (21-mg patch, one daily), or placebo e-cigarettes (no nicotine) from 1 week before until 12 weeks after quit day, with low-intensity behavioral support via voluntary telephone counseling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement less than 10 ppm). Primary analysis was by intention to treat.

A total of 657 people were randomized (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes). At 6 months, verified abstinence was 7.3% (21 of 289) with nicotine e-cigarettes, 5.8% (17 of 295) with patches, and 4.1% (3 of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1.51 [95% CI = –2.49 to 5.51]; for nicotine e-cigarettes vs placebo e-cigarettes 3.16 [95% CI = –2.29 to 8.61]). Achievement of abstinence was substantially lower than anticipated for the power calculation, so there was insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. However, they were at least as effective as patches. Importantly, we found no evidence of an association between adverse events and study product.

We concluded that e-cigarettes, with or without nicotine, were modestly effective at helping smokers quit, with similar achievement of abstinence as with nicotine patches, and few adverse events.

At 6 months, 29% of the nicotine e-cigarettes group and 35% of the placebo e-cigarettes group persisted with e-cigarette use, while only 8% in the patches group were still using patches. Among those in the nicotine e-cigarettes group verified as abstinent, 38% still used e-cigarettes at 6 months; among non-quitters, 29% still used e-cigarettes. The e-cigarette users were very enthusiastic about them: 85% of participants allocated to e-cigarettes would recommend them to a friend wanting to quit, and 40% liked their tactile cigarette-like qualities, sensory familiarity, perceived health benefits, taste, absence of cigarette odor, and ease of use.

Our research showed they are at least as effective and safe as the NRT patch for helping people quit in the short term. Following a risk to benefit assessment, they may be an option for smokers who have tried all other evidence-based treatments yet repeatedly relapsed to smoking, or for those whose behavioral dependence is a major feature of their addiction to cigarettes.

If e-cigarettes are being considered for patients using psychiatric medications, the same cautions would apply as for prescribing NRT. Stopping smoking affects the metabolism of a number of drugs used in the management of mental illness. Tobacco smoke contains substances such as polycyclic aromatic hydrocarbons that lead to increased expression of cytochrome P-450  enzymes in the liver and other tissues. Patients who are taking clozapine or olanzapine who stop smoking should have their drug levels monitored and their doses lowered when they stop smoking, some experts suggest by approximately 35%.14 The need for dosage adjustment with other psychiatric medications is not as strong.

E-cigarettes therefore may have a role in tobacco dependence treatment, but more research is needed to establish benefits and potential harms when used beyond 6 to 12 months, as seems to be commonplace-around one-third of users in our study. To improve efficacy and safety, the unreliability of many of these devices, the lack of quality controls in liquid manufacture, and child-proofing of the liquid containers will probably need to be addressed by light-touch regulatory means.

More broadly, the place of e-cigarettes in population-level tobacco control is debated. Could they be the breakthrough product needed to save millions of lives if used as low-harm substitutes for tobacco cigarettes? Or, could they “re-normalize” smoking behavior and be a gateway to tobacco for many people? Sensible, research-informed regulation is needed, sufficient to ensure public safety while at the same time not cutting off what may be a lifeline for the many smokers who have tried to quit repeatedly using the full range of standard tobacco dependence treatments, but have failed to do so.


Dr Bullen is Associate Professor at the University of Aukland New Zealand and Director of the National Institute for Health Innovation. He reports no conflicts of interest concerning the subject matter of this article. For a pdf of the study in The Lancet,please click here.


1. Purkayastha D. BAT ramps-up e-cigarette expansion as sales go up in smoke interna. International Business Times. July 31, 2013. Accessed November 20, 2013.
2. West R. Smoking toolkit study: monthly tracking of key performance indicators. July 20, 2012. Accessed November 20, 2013.
3. Hajek P, Foulds J, Houezec JL, et al. Should e-cigarettes be regulated as a medicinal device? Lancet Respir Med. 2013;1:429–431.
4. Cobb NK, Cobb CO. Regulatory challenges for refined nicotine products. Lancet Respir Med 2013;1:431–433.
5. Etter JF. Electronic cigarettes: a survey of users. BMC Public Health. 2010;10:231.
6. Dawkins L, Turner J, Roberts A, Soar K. ‘Vaping’ profiles and preferences: an online survey of electronic cigarette users. Addiction. 2013;108:1115–1125.
7. Bullen C, McRobbie H, Thornley S, et al. Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tob Control. 2010;19:98–103.
8. Vansickel A, Eissenberg T. Electronic cigarettes: effective nicotine delivery after acute administration. Nicotine Tob Res. 2013;15:267–270.
9. 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:e66317.
10. US Food and Drug Administration (FDA). Summary of results: laboratory analysis of electronic cigarettes conducted by FDA. Accessed November 20, 2013.
11. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2013 Mar 6; [Epub ahead of print].
12. Burstyn I. Peering through the mist: what does the chemistry of contaminants in electronic cigarettes tell us about health risks? Technical report. July-August 2013.  Accessed November 20, 2013.
13. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: randomised controlled trial. Lancet. 2013;382:1629-1637.
14. Wenzel-Seifert K, Koestlbacher A, Haen E. Dose-dependent effects of cigarette smoking on serum concentrations of psychotropic drugs. Ther Drug Monit. 2011;33:481-482.