smoking cessation

What’s neW in smoking cessation

What’s new in ...

stephen sutton

smoking cessation

current first-line treatments for smoking cessation are nicotine replacement therapy (nRt) and buproprion (an anti-depressant), which approximately double the odds of long-term cessation. the search continues for new pharmacological treatments that are safe, more effective than existing medications, and preferably less expensive. a new drug, varenicline, was recently licensed as a cessation aid. a drug called cytisine, which has been used as a cessation aid for several decades in eastern and central europe and is very inexpensive to produce, may be effective for smoking cessation but needs to be tested in more rigorous trials. there is evidence from pharmacogenetic research that variability in responsiveness to nRt is partly explained by genotype, suggesting that genetic tests could be used to tailor the dose or type of nRt. such a strategy would increase the cost and complexity of treatment, compared with offering all smokers the single most effective treatment, so its cost-effectiveness needs to be evaluated. early trials of nicotine vaccines have shown promising results, but further development and testing will be required before they can be licensed for use. approaches to smoking cessation that use the new communication media (internet, mobile phones) are also being developed. although there are unlikely to be major breakthroughs, new treatments for smoking cessation may be identified that are more effective or more widely applicable than existing treatments. alongside the development of new treatments, there are potentially important gains to be made by maximizing the use of existing treatments and resources.

Keywords bupropion; cytisine; new communication media; nicotine replacement; nicotine vaccines; pharmacogenetics; smoking cessation; varenicline

Cigarette smoking remains the leading cause of preventable disease and death in the world. In Great Britain, the preva-lence of smoking has fallen substantially over the last three decades, though the rate of decrease has slowed in recent years (Figure 1).1 In 2005, 25% of men and 23% of women were current cigarette smokers. There are marked differences in the prevalence of smoking depending on socioeconomic group. For example, in England in 2005, 29% of those in manual occupations were cigarette smokers com-pared with 19% of those in non-manual occupations.1

Most smokers are addicted to nico-tine, the main psychoactive ingredient in cigarette smoke. Smoking is main-tained by the primary pharmacological effects of nicotine and, probably more

meDicine 36:4

importantly, through relief of nicotine withdrawal.2 The majority of smokers say that they would like to quit smok-ing and that they have tried at least once to do so, but it is estimated that only 2–3% a year succeed in stopping smok-ing permanently.3

Current recommendations

Current first-line treatments for smoking cessation are nicotine replacement ther-apy (NRT) and buproprion. A range of different NRT products are available on prescription or over-the-counter, includ-ing gum, patches, lozenges, tablets, nasal spray and inhalers. They work by replacing some of the nicotine that smokers would otherwise have obtained from cigarettes. A meta-analysis of 123

226

randomized controlled trials showed that NRT almost doubles the odds of long-term cessation.4 Combining the nicotine patch with gum or nasal spray may be more effective than using the patch on its own.

Buproprion (marketed as Zyban) is an antidepressant. There is a link between smoking and depression, which provides a broad rationale for the use of antide-pressants as cessation aids, although the precise mechanism by which buproprion works is not yet known. A meta-analysis of 31 trials showed that buproprion approximately doubles the odds of cessa-tion.5 Further evidence is needed to clar-ify whether combining buproprion with NRT is more effective than using either agent on its own.

Current National Institute for Health and Clinical Excellence (NICE) guidelines on the use of NRT and buproprion are shown in Table 1.6 It is important to note that pharmacotherapy is more effective if it involves behavioural support.

Stephen Sutton BA MSc PhD CPsychol is Professor of Behavioural Science at the University of

Cambridge, UK. He trained in social psychology at the University of London and Computer

Science at City University. Competing interests: none declared.

© 2007 elsevier Ltd. all rights reserved.


Year

????

60

40

50

30

10

MenWomen

20

0

19741984

19821980

19781976

19861988

19901992

19941996

19982002

20002004

Prevalence of cigarette smoking: Great Britain1974 to 2005

Adapted from Goddard E. The General Household Survey 2005: Smoking and drinking among adults, 2005. London: Office for National Statistics, 2006.1

Figure 1 Prevalence

of cigarette smoking:

great Britain 1974 to

2005

NICE guidance on the use of nicotine replacement therapy (NRT) and buproprion for smoking cessation

1. guidance

1.1 nicotine replacement therapy (nRt) and bupropion are recommended for smokers who

have expressed a desire to quit smoking.

1.2 nRt or bupropion should normally only be prescribed as part of an abstinent-

contingent treatment (act), in which the smoker makes a commitment to stop

smoking on or before a particular date (target stop date). smokers should be offered

advice and encouragement to aid their attempt to quit. ideally, initial prescription

of nRt or bupropion should be sufficient to last only until 2 weeks after the target

stop date. normally, this will be after 2 weeks of nRt therapy, and 3-4 weeks for

bupropion, to allow for the different methods of administration and mode of action.

second prescriptions should be given only to people who have demonstrated that

their quit attempt is continuing on reassessment.

1.3 it is recommended that smokers who are under the age of 18 years, who are pregnant

or breastfeeding, or who have unstable cardiovascular disorders, should discuss the

use of nRt with a relevant health-care professional before it is prescribed.

1.4 Bupropion is not recommended for smokers under the age of 18 years, as its safety

and efficacy have not been evaluated for this group. Women who are pregnant or

breastfeeding should not use bupropion.

1.5 if a smoker's attempt to quit is unsuccessful with treatment using either nRt or

bupropion, the nhs should normally fund no further attempts within 6 months.

however, if external factors interfere with an individual's initial attempt to stop

smoking, it may be reasonable to try again sooner.

1.6 there is currently insufficient evidence to recommend the use of an nRt and

bupropion in combination.

1.7 in deciding which of the available therapies to use and in which order they should be

prescribed, practitioners should take into account:

• intention and motivation to quit, and likelihood of compliance

• the availability of counselling or support

• Previous usage of smoking cessation aids

• contraindications and potential for adverse effects

• Personal preferences of the smoker

available at: http://www.nice.org.uk/ta039.

Table 1

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New drugs

The search continues for new pharma-cological treatments that are safe, more effective than existing medications and, preferably, less expensive. A new drug, varenicline (Champix), was recently licensed in the UK as a cessation aid. Two meta-analyses of randomized controlled trials showed that varenicline is more effective than placebo (increasing the odds of quitting by a factor of about 3) and buproprion.5,7 Indirect comparisons showed that varenicline is more effective than NRT.7 NICE guidance on the use of varenicline was published in July 2007.8

Recently, a drug called cytisine has attracted the attention of tobacco research-ers. Cytisine is a natural insecticide present in several plants (e.g. Cytisus laburnum). It has a molecular structure somewhat similar to that of nicotine and, like vareni-cline, it is a partial agonist of nicotinic ace-tylcholine receptors in the brain. Cytisine has been used as a smoking cessation drug for several decades in East and Central European countries, where it is marketed as Tabex. It is very inexpensive to pro-duce. A recent review and meta-analysis of clinical studies, all conducted in Eastern Europe or Russia, concluded that cytisine may be effective for smoking cessation but that it needs to be tested in more rigorous trials.9

The pharmacogenetics of smoking cessation

Pharmacogenetic approaches use genetic information to tailor pharmacological treatment to the individual. There is evi-dence that variability in responsiveness to NRT is partly explained by genotype. For example, smokers with a particular vari-ant in the mu-opioid receptor (OPRM1) gene (Asp40, present in about 25% of the population) that regulates the binding affinity of beta-endorphins, have double the short-term quit rates when using a form of NRT with higher levels of replace-ment (transdermal nicotine patch) com-pared with a form of NRT that results in lower levels of replacement (nasal spray). Those homozygous for the more common variant (Asn40) were equally likely to stop smoking regardless of the level of nicotine replacement.10 These results support the hypothesis that smokers with one or more copies of the Asp40 variant are more likely


http://www.nice.org.uk/ta039


to stop smoking following higher doses of NRT than are smokers without this vari-ant, suggesting that dose or type of NRT could be tailored to genotype. There is also evidence that a polymorphism in the dopamine D2 receptor (DRD2) influences responsiveness to nicotine patches, but only among women.11

Research on the pharmacogenetics of smoking cessation is at a relatively early stage, and such findings are unlikely to lead to changes in how NRT and bupro-prion are prescribed in the near future, although a pharmacogenetic test for nico-tine dependence (Nicotest: G-nostics Ltd, www.nicotest.com) is already available commercially in the UK to help smokers to decide whether to use nicotine or non-nicotine products in a quit attempt.

The rationale for tailoring treatment to genotype is that it will improve treatment effectiveness compared with offering all smokers the single most effective treat-ment. However, such treatment match-ing increases the cost and complexity of treatment, so key questions that need to be addressed in future research are how much additional benefit does treatment matching provide and is the additional benefit worth the increased cost.12

Before the results of pharmacogenetic research are translated into clinical prac-tice, careful consideration also needs to be given to how genetic test results are communicated to smokers, otherwise the potential benefits may not material-ize. Smokers in an experimental study who were asked to imagine that they had a gene variant that predicted a good response to buproprion were more likely to select this drug to help them to quit; however, they were less likely to regard ‘willpower’ as important.13

Nicotine vaccines

Several companies are developing nico-tine vaccines that work by producing antibodies that bind to nicotine and pre-vent it from crossing the blood−brain barrier and producing its full pharmaco-logical effects.14 Nicotine vaccines may be effective in preventing relapse in recent ex-smokers as well as helping current smokers to quit. Early trials of two vac-cines, NicVAX (Nabi, Florida, USA) and NicQb (Cytos, Zurich, Switzerland), have shown promising results, but further development and testing will be required

meDicine 36:4

before they can be licensed for use as smoking cessation treatments. Vaccina-tion requires a series of intramuscular injections, a quite different regimen from the daily self-dosing required with NRT and other pharmacological treatments. Adherence to treatment may therefore be less of a problem than with pharmacolog-ical approaches.

Exploiting the new communication technologies

Self-help approaches to smoking ces-sation have traditionally used printed materials (and sometimes audio- or vid-eotapes) that are given or sent through the post to smokers, with little or no formal face-to-face contact with health professionals. These materials were typi-cally generic (all smokers received the same information) or targeted such that different categories of smokers (e.g. preg-nant women) received different versions of the materials. In recent years, several computer programs have been written that enable printed materials to be indi-vidually tailored to the characteristics of the smoker.15 In this approach, infor-mation is collected from the smoker, by questionnaire or interview, the informa-tion is scanned into a database, and the computer program then generates a tai-lored advice report that can be given or sent to the smoker. Such systems enable a very high degree of tailoring; for exam-ple, one system can generate over 3,300 million unique advice reports, based on responses to a 30-item questionnaire that assesses demographic characteristics, smoking habits, smoking history, motiva-tion to quit, reasons for quitting, difficult situations, current health problems, and social environment.16

There are now more than 100 web-sites that provide smoking cessation advice in one form or another to smok-ers who, in contrast to the tailoring sys-tems just described, interact directly with the computer. Most of these sites do not fully exploit the capability of the tech-nology to provide highly tailored advice and to invite the smoker to re-visit the site to receive progress reports and ongo-ing support. To date, there have been few evaluation studies,17,18 so it is dif-ficult to know how effective web-based approaches are, or even what kinds of smokers use them.

228

Access to the internet is related to socioeconomic status – an example of the ‘digital divide’ − leading to a com-monly expressed concern that web-based programs may contribute to maintaining or increasing health inequalities. The evi-dence suggests that access to the internet is strongly related to age, with younger people being more likely to have access than older people. Web-based programs may therefore provide a way of reaching younger smokers.

Mobile phone technology is also being used as a medium for providing advice and support for smoking cessation. A New Zea-land trial of mobile phone texting aimed at younger smokers yielded encouraging findings,19 and this system ('txt2stop') is now being evaluated in the UK.

Conclusions

Development of new treatments for smok-ing cessation is an active research area. Because smoking is a complex behaviour influenced by multiple psychological, biological and social factors, there are unlikely to be major breakthroughs. Nev-ertheless, new treatments may be identi-fied that are more effective or more widely applicable than existing treatments. The ever increasing range of treatments also increases the possibilities for tailoring treatments to individual smokers and for treating smokers who have unsuccessfully tried to quit using existing treatments.

Alongside the development of new treatments, there are potentially important gains to be made by maximizing the use of existing treatments and resources. For example, most smokers who use NRT do not use enough of it or do not use it for long enough. Improving adherence to NRT may increase success rates. Similarly, if primary healthcare professionals increased their rates of referring smokers to the NHS stop smoking services, this would increase the yield of ex-smokers. ◆

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