ABC OF SMOKING CESSATION - archive.org · ABC OF SMOKING CESSATION Edited by JOHN BRITTON Professor of Epidemiology at the University of Nottingham ABSC-FM.qxd 21/6/04 2:38 PM Page

ABC OF SMOKING CESSATION

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ABC OF SMOKING CESSATION

Edited by

JOHN BRITTON

Professor of Epidemiology at the University of Nottingham

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© 2004 by Blackwell Publishing LtdBMJ Books is an imprint of the BMJ Publishing Group Limited, used under licence

Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USABlackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UKBlackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia

The right of the Author to be identified as the Author of this Work has been asserted in accordance with the Copyright, Designs and Patents Act 1988.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.

First published 2004

ISBN 0 7279 1818 4

A catalogue record for this title is available from the British Library and the Library of Congress

The cover shows a No Smoking sign. With permission from Dennis Potokar/Science Photo Library

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Contents

Contributors vii

Preface ix

1 The problem of tobacco smoking 1Richard Edwards

2 Why people smoke 4Martin J Jarvis

3 Assessment of dependence and motivation to stop smoking 7Robert West

4 Use of simple advice and behavioural support 9Tim Coleman

5 Nicotine replacement therapy 12Andrew Molyneux

6 Bupropion and other non-nicotine pharmacotherapies 15Elin Roddy

7 Special groups of smokers 18Tim Coleman

8 Cessation interventions in routine health care 21Tim Coleman

9 Setting up a cessation service 24Penny Spice

10 Population strategies to prevent smoking 27Konrad Jamrozik

11 Harm reduction 31Ann McNeill

12 Economics of smoking cessation 34Steve Parrott, Christine Godfrey

13 Policy priorities for tobacco control 37Konrad Jamrozik

Index 41

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John BrittonProfessor of Epidemiology at the University of Nottingham inthe division of epidemiology and public health at City Hospital,Nottingham

Tim ColemanSenior Lecturer in general practice at the School of Community Health Sciences in the Division of Primary Care at University Hospital, Queen’s Medical Centre, Nottingham

Richard EdwardsSenior Lecturer in public health in the Evidence for Population Health Unit at the Medical School, University of Manchester

Christine GodfreyProfessor of Health Economics at the Department of HealthSciences and Centre for Health Economics at the University of York

Konrad JamrozikProfessor of Primary Care Epidemiology, Imperial College,London, and Visiting Professor in Public Health, School ofPopulation Health, University of Western Australia, Perth

Martin J JarvisProfessor of Health Psychology in the Cancer Research UKHealth Behaviour Unit, Department of Epidemiology andPublic Health at the University College London

Ann McNeillIndependent consultant in public health and Honorary SeniorLecturer in the Psychology Department at St George’s HospitalMedical School, London

Andrew MolyneuxConsultant respiratory physician at the Sherwood ForestHospitals Trust, Nottinghamshire

Steve ParrottResearch Fellow at the Centre for Health Economics at theUniversity of York

Elin RoddyClinical Research Fellow at the University of Nottingham in the Division of Respiratory Medicine at City Hospital,Nottingham

Penny SpiceHead of Public Involvement at Rushcliffe Primary Care Trustand formerly smoking cessation coordinator at NottinghamHealth Authority

Robert WestProfessor of Health Psychology in the Cancer Research UKHealth Behaviour Unit, Department of Epidemiology andPublic Health at the University College London

Contributors

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ix

Preface

Smoking kills more people than any other avoidable factor in developed countries. Smoking cessation has a substantial positiveimpact on quantity and quality of life expectancy in all smokers, and smoking cessation interventions are among the most costeffective interventions available in medicine. It is therefore surprising that in many countries, smoking cessation measures are notroutinely available or are not widely used to help smokers to quit smoking. Most medical schools do not train doctors properly totreat smoking, and many doctors and other health professionals are still unfamiliar with the basic underlying principles of smokingas an addictive behaviour, and with methods of intervening to help smokers to quit.

This book is intended to provide the basic, simple information needed to equip all health professionals to intervene effectively,efficiently, and constructively to help their patients to stop smoking. The book describes how and why people start smoking, why theycontinue to smoke, and what to do to help them to stop. We describe methods of ensuring that identifying and treating smokingbecomes a routine component of health care, and because the best results are generally achieved by specialist smoking cessationservices we describe some of the challenges and difficulties of establishing these facilities. As prevention of smoking in populationsis such an important determinant of individual motivation to quit or avoid smoking, the authors summarise the population strategiesand political policies that can help drive down the prevalence of smoking. For our managers, this ABC covers the cost-effectivenessof these initiatives.

One of the tragedies of modern clinical medicine is that treating smoking is so simple, has so much to offer, and so often is notdone. The methods are not difficult. This book explains them.

John Britton

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1 The problem of tobacco smokingRichard Edwards

Cigarette smoking is the single biggest avoidable cause of deathand disability in developed countries. Smoking is nowincreasing rapidly throughout the developing world and is oneof the biggest threats to current and future world health. Formost smokers, quitting smoking is the single most importantthing they can do to improve their health. Encouragingsmoking cessation is one of the most effective and cost effectivethings that doctors and other health professionals can do toimprove health and prolong their patients’ lives. This book willexplore the reasons why smokers smoke, how to help them toquit, and how to reduce the prevalence of smoking moregenerally.

Who smokes tobacco?Cigarette smoking first became a mass phenomenon in theUnited Kingdom and other more affluent countries in the early20th century after the introduction of cheap, mass produced,manufactured cigarettes. Typically, a “smoking epidemic” in apopulation develops in four stages: a rise and then decline insmoking prevalence, followed two to three decades later by asimilar trend in smoking related diseases. Usually, the uptakeand consequent adverse effects of smoking occur earlier and toa greater degree among men.

In the United Kingdom there are about 13 million smokers,and worldwide an estimated 1.2 billion. Half of these smokerswill die prematurely of a disease caused by their smoking, losingan average of eight years of life; this currently represents fourmillion smokers each year worldwide. Deaths from smoking areprojected to increase to more than 10 million a year by 2030, bywhich time 70% of deaths will be in developing countries.

The prevalence of smoking among adults in the UnitedKingdom has declined steadily from peaks in the 1940s in menand the late 1960s in women. However, this reduction in overallprevalence during stage 4 of the epidemic disguises relativelystatic levels of smoking among socioeconomicallydisadvantaged groups, making smoking one of the mostimportant determinants of social inequalities in health in thedeveloped world. Smoking has also declined much more slowlyamong young adults in the United Kingdom. The decline insmoking in the United Kingdom and some other developedcountries may now be coming to an end. For example, since1994 the prevalence of smoking in UK adults has remained atabout 28%.

Whereas countries in western Europe, Australasia, and theUnited States may be in stage 4 of the smoking epidemic, inmany developing countries the epidemic is just beginning.Smoking in low and middle income countries is increasingrapidly—for example, the prevalence of smoking among malesin populous Asian countries is now far higher than in Westerncountries—45% in India, 53% in Japan, 63% in China, 69% inIndonesia, and 73% in Vietnam.

Adverse health effectsThe adverse health effects of smoking are extensive, and havebeen exhaustively documented. There is a strong dose-response

Stage 1Sub-Saharan

Africa

Stage 4Western Europe,North America,

Australia

Stage 2China, Japan,

South East Asia,Latin America,

north Africa

Stage 3Eastern Europe,

southern Europe,Latin America

Stage 1 Stage 4Stage 2 Stage 3

% o

f sm

oker

s am

ong

adul

ts

0 10 20 30 40 50 60 70 80 90 100Years

0

20

30

40

50

60

70

10 % o

f dea

ths

caus

ed b

y sm

okin

g

0

20

30

40

10

Male smokers

Female smokers

Male deaths

Female deaths

Stages of worldwide tobacco epidemic. Adapted from Lopez et al. Adescriptive model of the cigarette epidemic in developed countries. TobaccoControl 1994;3:242-7

Year

% o

f UK

adul

ts s

mok

ing

man

ufac

ture

d ci

gare

ttes

1952 19561948 1960 1964 1968 1972 1976 1980 1984 1988 1992 1996 20000

20

30

40

50

60

70

10

Men

Women

Prevalence of smoking of manufactured cigarettes in Great Britain. Datafrom Tobacco Advisory Council (1948-70) and general household survey(1972-2001)

Deprivation score

Prev

alen

ce o

f sm

okin

g in

pop

ulat

ion

(%)

0

PoorestMost affluent

0

20

30

40

50

60

70

80

10

1973

1993

1 2 3 4 5

Cigarette smoking by deprivation level in Great Britain. Data from generalhousehold survey

1

relation with heavy smoking, duration of smoking, and earlyuptake associated with higher risks of smoking related diseaseand mortality. Data from 40 years of follow up of smokers in aprospective cohort study of male British doctors show theimpact of smoking on longevity at different levels of exposure.The strongest cause-specific associations are with respiratorycancers and chronic obstructive pulmonary disease; in numericterms, the greatest health impacts of smoking are on respiratoryand cardiovascular diseases.

Some of the increases in health risk associated with smokingare greater among younger smokers. The risk of heart attackamong smokers, for example, is at least double over the age of60 years, but those aged under 50 have a more than fivefoldincrease in risk. Smokers are also at greater risk of many othernon-fatal diseases, including osteoporosis, periodontal disease,impotence, male infertility, and cataracts. Smoking in pregnancyis associated with increased rates of fetal and perinatal deathand reduced birth weight for gestational age. Passive smokingafter birth is associated with cot death and respiratory disease inchildhood and lung cancer, heart disease, and stroke in adults.

The effect on health services is considerable—for example,an estimated 364 000 admissions and £1.5bn ($2.4bn; €2.1bn) ayear in health service costs are attributable to smoking in theUnited Kingdom alone.

Health benefits of smoking cessationStopping smoking has substantial immediate and long termhealth benefits for smokers of all ages. The excess risk of deathfrom smoking falls soon after cessation and continues to do sofor at least 10-15 years. Former smokers live longer thancontinuing smokers, no matter what age they stop smoking,though the impact of quitting on mortality is greatest atyounger ages. For smokers who stop before age 35, survival isabout the same as that for non-smokers.

The rate and extent of reduction of risk varies betweendiseases—for lung cancer the risk falls over 10 years to about30%-50% that of continuing smokers, but the risk remainsraised even after 20 years of abstinence. There is benefit fromquitting at all ages, but stopping before age 30 removes 90% ofthe lifelong risk of lung cancer. The excess risk of oral andoesophageal cancer caused by smoking is halved within fiveyears of cessation.

The risk of heart disease decreases much more quickly afterquitting smoking. Within a year the excess mortality due tosmoking is halved, and within 15 years the absolute risk isalmost the same as in people who have never smoked. In ameta-analysis by Wilson and colleagues in 2000, the odds ratiofor death for smokers who stopped smoking after myocardialinfarction was 0.54, a far higher protective effect than the0.75-0.88 odds ratio for death achieved by the conventionalstandard treatments for myocardial infarction, includingthrombolysis, aspirin, � blockers, and statins. Smoking cessationalso reduces the risk of death after a stroke and of death frompneumonia and influenza.

Smoking is associated with an accelerated rate of decline inlung function with age. Cessation results in a small increase inlung function and reverses the effect on subsequent rate ofdecline, which reverts to that in non-smokers.

Thus, early cessation is especially important in susceptibleindividuals to prevent or delay the onset of chronic obstructivepulmonary disease. In patients with this disease, mortality andsymptoms are reduced in former smokers compared withcontinuing smokers. Recent evidence shows that the benefits

Age

% o

f stu

dy d

octo

rs a

live

40 55 70 85 1000

20

40

60

80

100

Current cigarette smokers:

1-14 a day

15-24 a day

> 25 a day

Never smoked regularly

Survival by smoking status, according to study of male British doctors(follow up after 40 years, 1951-91). Adapted from Doll et al (see FurtherReading box)

No o

f dea

ths

(000

s) a

ttrib

utab

le to

sm

okin

g, 1

995

Rela

tive

risk

of d

eath

0

10

15

20

25

30

Lung

canc

er

Oeso

phag

eal c

ance

r

Bladd

er ca

ncer

Throa

t and

mou

th ca

ncer

Ischa

emic

heart

dise

ase

Strok

e

Aortic

aneu

rysm

Chron

ic bro

nchit

is

and e

mphy

sema

Pneu

monia

5

0

10

15

20

25

30

5

Smoking attributable deaths Relative risk of death

Numbers and relative risk of death (by cause) due to smoking, UnitedKingdom. Data from Tobacco Advisory Group of the Royal College ofPhysicians and Doll et al (see Further Reading box)

FEV 1

(litr

es)

2.0

2.2

2.4

2.6

2.8

3.0

Years of study

FEV 1

(% o

f pre

dict

ed n

orm

al v

alue

)

0

FEV1 = forced expiratory volume in one second

1 2 3 4 5 6 7 8 9 10 1160

65

70

75

80

85

Sustained quitters

Intermittent smokers

Continuous smokers

Effect of smoking cessation on rate of decline in lung function in chronicobstructive pulmonary disease. Adapted from Anthonisen et al. Am J RespirCrit Care Med 2002;166:675-9

ABC of Smoking Cessation

2

occur even in older patients with severe chronic obstructivepulmonary disease.

At a population level, the importance of smoking cessationis paramount. Peto has estimated that current cigarette smokingwill cause about 450 million deaths worldwide in the next 50years. Reducing current smoking by 50% would prevent 20-30million premature deaths in the first quarter of this century andabout 150 million in the second quarter. Preventing youngpeople from starting smoking would have a more delayed butultimately even greater impact on mortality.

Effective prevention of cigarette smoking and help for thosewishing to quit can therefore yield enormous health benefits forpopulations and individuals. Promoting and supportingsmoking cessation should be an important health policypriority in all countries and for healthcare professionals in allclinical settings. However, this has not so far generally beenreflected at a policy level or in the practice of individualhealthcare professionals.

Competing interests: RE is chairman of North West ASH (Action onSmoking and Health); he receives no financial reward for this work. JB hasbeen reimbursed by GlaxoWellcome (now GlaxoSmithKline) for attendingtwo international conferences, has received a speaker’s honorarium fromGlaxoWellcome, and has been the principal investigator in a clinical trialof nicotine replacement therapy funded by Pharmacia. Both thesecompanies manufacture nicotine replacement products.

Further readingx Tobacco Advisory Group of the Royal College of Physicians.

Nicotine addiction in Britain. London: Royal College of Physicians ofLondon, 2000. www.rcplondon.ac.uk/pubs/books/nicotine/index.htm

x Jha P, Chaloupka F, eds. Tobacco control in developing countries.Oxford: Oxford University Press, 1999.

x Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality inrelation to smoking: 40 years’ observations on male British doctors.BMJ 1994;309:901-11.

x World Bank. Curbing the epidemic: governments and the economics oftobacco control. Washington, DC: World Bank, 1999.www1.worldbank.org/tobacco/reports.asp

x US Department of Health and Human Services. The health benefitsof smoking cessation: a report of the surgeon general. Rockville, MD: USGovernment Printing Office, 1990. (DHHS publication No (CDC)90-8416.)

x Wilson K, Willan A, Cook D. Effect of smoking cessation onmortality after myocardial infarction. Arch Intern Med2000;160:939-44.

Stopping smoking before or in the first three to fourmonths of pregnancy protects the fetus against thereduced birth weight associated with smoking.Preoperative cessation reduces perioperative mortalityand complications

Key pointsx Cigarette smoking is one of the greatest avoidable causes of

premature death and disability in the worldx Helping smokers to stop smoking is one of the most cost effective

interventions available in clinical practicex Promoting smoking cessation should therefore be a major priority

in all countries and for all health professionals in all clinical settings

The problem of tobacco smoking

3

2 Why people smokeMartin J Jarvis

For much of the 20th century, smoking was regarded as asocially learned habit and as a personal choice. It is only in thepast decade or so that the fundamental role of nicotine insustaining smoking behaviour has begun to be more widelyaccepted. It is now recognised that cigarette smoking isprimarily a manifestation of nicotine addiction and thatsmokers have individually characteristic preferences for theirlevel of nicotine intake. Smokers regulate the way they puff andinhale to achieve their desired nicotine dose.

The link with nicotine addiction does not imply thatpharmacological factors drive smoking behaviour in a simpleway and to the exclusion of other influences. Social, economic,personal, and political influences all play an important part indetermining patterns of smoking prevalence and cessation.Although drug effects underpin the behaviour, family and widersocial influences are often critical in determining who startssmoking, who gives up, and who continues.

Why do people start smoking?Experimenting with smoking usually occurs in the early teenageyears and is driven predominantly by psychosocial motives. Fora beginner, smoking a cigarette is a symbolic act conveyingmessages such as, in the words of the tobacco company PhilipMorris, “I am no longer my mother’s child,” and “I am tough.”Children who are attracted to this adolescent assertion ofperceived adulthood or rebelliousness tend to come frombackgrounds that favour smoking (for example, with high levelsof smoking in parents, siblings, and peers; relatively deprivedneighbourhoods; schools where smoking is common). Theyalso tend not to be succeeding according to their own orsociety’s terms (for example, they have low self esteem, haveimpaired psychological wellbeing, are overweight, or are poorachievers at school).

The desired image is sufficient for the novice smoker totolerate the aversion of the first few cigarettes, after whichpharmacological factors assume much greater importance.Again in the words of Philip Morris, “as the force from thepsychosocial symbolism subsides, the pharmacological effecttakes over to sustain the habit.” Within a year or so of starting tosmoke, children inhale the same amount of nicotine percigarette as adults, experience craving for cigarettes when theycannot smoke, make attempts to quit, and report experiencingthe whole range of nicotine withdrawal symptoms.

Physical and psychological effects ofnicotineAbsorption of cigarette smoke from the lung is rapid andcomplete, producing with each inhalation a high concentrationarterial bolus of nicotine that reaches the brain within 10-16seconds, faster than by intravenous injection. Nicotine has adistributional half life of 15-20 minutes and a terminal half lifein blood of two hours. Smokers therefore experience a patternof repetitive and transient high blood nicotine concentrationsfrom each cigarette, with regular hourly cigarettes needed tomaintain raised concentrations, and overnight blood levelsdropping to close to those of non-smokers.

Smoking a cigarette for a beginner is a symbolic act of rebellion

“If it were not for the nicotine in tobaccosmoke, people would be little moreinclined to smoke than they are to blowbubbles”

M A H Russell, tobacco researcher, 1974

By age 20, 80% of cigarette smokers regret that they everstarted, but as a result of their addiction to nicotine, manywill continue to smoke for a substantial proportion oftheir adult lives

Time (minutes)

Nico

tine

conc

entra

tion

(ng/

ml)

0 10 20 30

Cigarette smoked

40 50 600

10

20

30

40

50Venous levelsArterial levels

Arterial and venous levels of nicotine during cigarette smoking

4

Nicotine has pervasive effects on brain neurochemistry. Itactivates nicotinic acetylcholine receptors (nAChRs), which arewidely distributed in the brain, and induces the release ofdopamine in the nucleus accumbens. This effect is the same asthat produced by other drugs of misuse (such as amphetaminesand cocaine) and is thought to be a critical feature of brainaddiction mechanisms. Nicotine is a psychomotor stimulant,and in new users it speeds simple reaction time and improvesperformance on tasks of sustained attention. However, toleranceto many of these effects soon develops, and chronic usersprobably do not continue to obtain absolute improvements inperformance, cognitive processing, or mood. Smokers typicallyreport that cigarettes calm them down when they are stressedand help them to concentrate and work more effectively, butlittle evidence exists that nicotine provides effective selfmedication for adverse mood states or for coping with stress.

A plausible explanation for why smokers perceive cigarettesto be calming may come from a consideration of the effects ofnicotine withdrawal. Smokers start to experience impairment ofmood and performance within hours of their last cigarette, andcertainly overnight. These effects are completely alleviated bysmoking a cigarette. Smokers go through this processthousands of times over the course of their smoking career, andthis may lead them to identify cigarettes as effective selfmedication, even if the effect is the negative one of withdrawalrelief rather than any absolute improvement.

Symptoms of nicotine withdrawalMuch of the intractability of cigarette smoking is thought tostem from the problems of withdrawal symptoms—particularlyirritability, restlessness, feeling miserable, impairedconcentration, and increased appetite—as well as from cravingsfor cigarettes. These withdrawal symptoms begin within hoursof the last cigarette and are at maximal intensity for the firstweek. Most of the affective symptoms then resolve over three orfour weeks, but hunger can persist for several months. Cravings,sometimes intense, can also persist for many months, especiallyif triggered by situational cues.

Social and behavioural aspectsThe primary reinforcing properties of nicotine ultimatelysustain smoking behaviour: in experimental models, if nicotineis removed from cigarette smoke, or nicotine’s effects on thecentral nervous system are blocked pharmacologically, smokingeventually ceases. However, under normal conditions, theintimate coupling of behavioural rituals and sensory aspects ofsmoking with nicotine uptake gives ample opportunities forsecondary conditioning. For a 20 a day smoker, “puff by puff”delivery of nicotine to the brain is linked to the sight of thepacket, the smell of the smoke, and the scratch in the throatsome 70 000 times each year. This no doubt accounts forsmokers’ widespread concern that if they stopped smoking theywould not know what to do with their hands, and for the abilityof smoking related cues to evoke strong cravings.

Social influences also operate to modulate nicotine’s effects.The direction of this influence can be to discouragesmoking—as, for example, with the cultural disapproval ofsmoking in some communities, the expectation of non-smokingthat has become the norm in professional groups, or the effectsof smoke-free policies in workplaces. Other factors encouragesmoking, such as being married to a smoker or being part ofsocial networks in socially disadvantaged groups, among whomprevalence is so high as to constitute a norm.

Effects of nicotine withdrawal

Symptom Duration Incidence (%)Lightheadedness < 48 hours 10Sleep disturbance < 1 week 25Poor concentration < 2 weeks 60Craving for nicotine < 2 weeks 70Irritability or aggression < 4 weeks 50Depression < 4 weeks 60Restlessness < 4 weeks 60Increased appetite < 10 weeks 70

Behavioural rituals are closely coupledwith sensory aspects of smoking

Many experimental and clinical studieshave shown that withdrawal symptomsare attributable to nicotine, as nicotinereplacement (by gum, patch, spray, orlozenge) reliably attenuates the severity ofwithdrawal

nAChR= nicotinic acetylcholine receptorNAcc= nucleus accumbensVTA= ventral tegmental areaNMDA= N-methyl-D-aspartate

Nicotine

Nicotine

NAccshell VTA

Raphénuclei

Pedunculopontinenucleus

DA

nAChR

nAChR

Nicotine

Nicotine

nAChR

nAChR

NMDA receptor

Glutamatergic efferents

Cholinergicefferents

NicotinenAChR

Pathways of nicotine reinforcement and addiction. Adapted from Watkinset al. Nicotine and Tobacco Research 2000;2:19-37

Why people smoke

5

Regulation of nicotine intakeSmokers show a strong tendency to regulate their nicotineintakes from cigarettes within quite narrow limits. They avoidintakes that are either too low (provoking withdrawal) or toohigh (leading to unpleasant effects of nicotine overdose). Withinindividuals, nicotine preferences emerge early in the smokingcareer and seem to be stable over time. The phenomenon ofnicotine titration is responsible for the failure of intakes todecline after switching to cigarettes with low tar and nicotineyields. Compensatory puffing and inhalation, operating at asubconscious level, ensure that nicotine intakes are maintained.As nicotine and tar delivery in smoke are closely coupled,compensatory smoking likewise maintains tar intake anddefeats any potential health gain from lower tar cigarettes.Similar compensatory behaviour occurs after cutting down onthe number of cigarettes smoked each day; hence this popularstrategy fails to deliver any meaningful health benefits.

Socioeconomic status and nicotineaddictionAn emerging phenomenon of the utmost significance over thepast two decades has been the increasing association ofcontinued smoking with markers of social disadvantage. Amongaffluent men and women in the United Kingdom, theproportion of ever smokers who have quit has more thandoubled since the early 1970s, from about 25% to nearly 60%,whereas in the poorest groups the proportion has remained ataround 10%. Part of the explanation for this phenomenon maybe found in the growing evidence that poorer smokers tend tohave higher levels of nicotine intake and are substantially moredependent on nicotine. It is evident that future progress inreducing smoking is increasingly going to have to tackle theproblems posed by poverty.

Smoking as a chronic diseaseCigarette dependence is a chronic relapsing condition that formany users entails a struggle to achieve long term abstinencethat extends over years or decades. Successful interventionsneed to tackle the interacting constellation of factors—personal,family, socioeconomic, and pharmacological—that sustain useand can act as major barriers to cessation.

The photo of children smoking is with permission from Ralph Mortimer/Rex, and the photo of the man smoking is with permission fromAlexandra Murphy/Photonica.

Cigarette nicotine yield (mg)

Nico

tine

inta

ke p

er c

igar

ette

(mg)

1.00

0.4

0.6

0.8

1.0

1.2

1.4

1.6

0.2

Actual Predicted

Regulation of nicotine intake: actual and predicted intake per cigarette fromlow tar cigarettes. Data from health survey for England, 1998

Deprivation score

Mea

n pl

asm

a co

tinin

e (n

g/m

l)

0 1 4 5Most affluent Poorest

2 30

250

300

350

200

Nicotine intake and social deprivation. Data from health survey for England(1993, 1994, 1996)

Smoking behaviour and cessationx The natural course of cigarette smoking is typically characterised by

the onset of regular smoking in adolescence, followed by repeatedattempts to quit

x Each year about a third of adult smokers in the United Kingdomtry to quit, usually unaided and typically relapsing within days

x In general, less than 3% of attempts to quit result in sustained (12months’) cessation, though the chances of success are slightlyhigher in women of childbearing age, parents of young children,and spouses of non-smokers

Key pointsx Smoking usually starts as a symbolic act of rebellion or maturityx By age 20, 80% of smokers regret having started to smokex Nicotine from cigarettes is highly addictive—probably because it is

delivered so rapidly to the brainx Smoking a cigarette, especially the first of the day, feels good

mainly because it reverses the symptoms of nicotine withdrawalx Most smokers who switch to low tar cigarettes or reduce the

number of cigarettes they smoke continue to inhale the sameamount of nicotine, and hence tar, from the cigarettes they smoke

x Heavy dependence on nicotine is strongly related to socioeconomicdisadvantage

x Smoking is a chronic relapsing addictive disease

Further readingx Royal College of Physicians. Nicotine addiction in Britain. London:

RCP, 2000.x Benowitz NL. Pharmacologic aspects of cigarette smoking and

nicotine addiction. N Engl J Med 1988;319:1318-30.x National Institutes of Health. Risks associated with smoking cigarettes

with low machine-measured yields of tar and nicotine. Bethesda, MD:Department of Health and Human Services, National Institutes ofHealth, National Cancer Institute, 2001. (NIH publication No02-5074.)

x Jarvis MJ. Patterns and predictors of unaided smoking cessation inthe general population. In: Bolliger CT, Fagerstrom KO, eds. Thetobacco epidemic. Basle: Karger, 1997:151-64.

Competing interests: MJJ has received speaker’s honorariums fromGlaxoSmithKline and Pharmacia. He is also director of an NHS fundedsmoking cessation clinic. See chapter 1 for the series editor’s competinginterests.

ABC of Smoking Cessation

6

3 Assessment of dependence and motivation to stopsmokingRobert West

Whether a smoker succeeds in stopping smoking depends onthe balance between that individual’s motivation to stopsmoking and his or her degree of dependence on cigarettes.Clinicians must be able to assess both of these characteristics.Motivation is important because “treatments” to assist withsmoking cessation will not work in smokers who are not highlymotivated. Dependence is especially important in smokers whodo want to stop smoking, as it influences the choice ofintervention. It is also important to bear in mind that:x Motivation to stop and dependence are often related to eachother: heavy smokers may show low motivation because theylack confidence in their ability to quit; lighter smokers mayshow low motivation because they believe they can stop in thefuture if they wishx Motivation to stop can vary considerably with time and bestrongly influenced by the immediate environmentx What smokers say about their wish to stop, especially in aclinical interview, may not accurately reflect their genuinefeelings.

Measuring dependence in smokersQualitative methodsThe simplest approach to measuring dependence on cigarettesis a basic qualitative approach that uses questions to find outwhether the smoker has difficulty in refraining from smoking incircumstances when he or she would normally smoke orwhether the smoker has made a serious attempt to stop in thepast but failed.

Quantitative methodsThe most commonly used quantitative measure of dependence isthe Fagerstrom test for nicotine dependence, which has provedsuccessful in predicting the outcome of attempts to stop. Thehigher the score on this questionnaire, the higher the level ofdependence: smokers in the general population score an averageof about 4 on this scale. Of all the items in the questionnaire,cigarettes per day and time to first cigarette of the day seem to bethe most important indicators of dependence.

Objective methodsThe concentration of nicotine or its metabolite, cotinine, inblood, urine, or saliva is often used in research as an objectiveindex of dependence because it provides an accurate measureof the quantity of nicotine consumed, which is itself a marker ofdependence. Carbon monoxide concentration of expired air isa measure of smoke intake over preceding hours; it is not asaccurate an intake measure as nicotine based measures, but it ismuch less expensive and gives immediate feedback to thesmoker.

How should dependence influence choice of treatment?The main value of measuring dependence in tailoring cessationinterventions to individual smokers is in the choice ofpharmacotherapy. The manufacturers of smoking cessationdrug products (principally nicotine replacement therapy andbupropion—see later chapters in this book) recommend that

• Likely to stop with minimal help• Primary intervention goal is to trigger a quit attempt

• Unlikely to stop but could do so without help• Primary intervention goal is to increase motivation

High

Motivation

Dependence

Low

Low

• Unlikely to stop without help but would benefit from treatment• Primary intervention goal is to engage smoker in treatment

• Unlikely to stop• Primary intervention goal is initially to increase motivation to make smoker receptive to treatment for dependence

High

Clinical intervention goals for smoking according to dependence andmotivation to quit

No/YesDo you find it difficult not to smoke in situations where you wouldnormally do so?

No/YesHave you tried to stop smoking for good in the past but found that youcould not?

A “yes” response to either of these questions would suggest that the smokermight benefit from help with stopping

10 or less11 to 2021 to 30

31 or more

0123

Q1. How many cigarettes per day do you usually smoke? (Write a number in the box and circle one response)

Within 5 minutes6-30 minutes31 or more

320

Q2. How soon after you wake up do you smoke your first cigarette? (Circle one response)

NoYes

01

Q3. Do you find it difficult to stop smoking in non-smoking areas? (Circle one response)

First of the morningOther

10

Q4. Which cigarette would you most hate to give up? (Circle one response)

NoYes

01

Q5. Do you smoke more frequently in the first hours after waking than the rest of the day? (Circle one response)

NoYes

01

Q4. Do you smoke if you are so ill that you are in bed most of the day? (Circle one response)

The Fagerstrom test for nicotine dependence: a quantitative index ofdependence. The numbers in the pink shaded column corresponding to thesmoker’s responses are added together to produce a single score on scale of0 (low dependence) to 10 (high dependence). Adapted from Heatherton etal. Br J Addict 1991;86:1119-27

This article reviews some simple methods to assessdependence and motivation in smokers

7

only smokers of 10 or more cigarettes a day should use theirproducts. However, the UK National Institute for ClinicalExcellence has recently recognised this cut off to be arbitraryand has not specified any particular lower limit for dailycigarette consumption.

Measuring motivation to stop smokingSurvey evidence in the United Kingdom shows that about twothirds of smokers declare that they want to stop smoking andthat in any year almost a third make an attempt to stop. Youngsmokers are widely believed to be less motivated to stop thanolder smokers, but in fact the reverse is true: older smokers aretypically less motivated.

However, only a minority of smokers attempting to stopcurrently use smoking cessation medications or attend aspecialist cessation service. This may reflect a lack of confidenceamong smokers that these treatments will help.

Direct questioningMotivation to stop can be assessed qualitatively by means ofsimple direct questions about their interest and intentions toquit. This simple approach is probably sufficient for mostclinical practice, although slightly more complex,semiquantitative measures (asking the smoker to rate degree ofdesire to stop on a scale from “not at all” to “very much”) canalso be used.

Stages of changeOne model of the process of behaviour change has becomepopular: the “transtheoretical model.” In this model, smokersare assigned to one of five stages of motivation:precontemplation (not wishing to stop), contemplation(thinking about stopping but not in the near future),preparation (planning to stop in the near future), action (tryingto stop), and maintenance (have stopped for some time).Smokers may cycle through the contemplation to action stagesmany times before stopping for good. This model has beenwidely adopted, though no evidence exists that the ratherelaborate questionnaires for assigning smokers to particularstages predict smoking cessation better than the simple directquestions outlined above.

Some clinicians use a smoker’s degree of motivation to stopas a prognostic indicator of likely success once the quit attempthas been decided. In fact, degree of motivation seems to play afairly small role in success; once a quit attempt is made, markersof dependence are far stronger determinants of success. Theultimate practical objective of assessing motivation is thereforeto identify smokers who are ready to make a quit attempt. Afterthat, it is the success of the intervention in overcomingdependence that matters.

Dependence and dose of nicotine in treatmentx The nicotine dose should be guided by measures of dependencex The higher strength forms of nicotine replacement are particularly

recommended for high dependence smokersx For nicotine therapy, high dependence smoking is typically

considered to be at least 15-20 cigarettes a day and/or smokingwithin 30 minutes of waking

Nicotine therapy will be covered in a later article in this series

Estimated prevalence of selected indices of motivation tostop smokingIndex % of

smokersWould like to stop smoking for good 70Intend to stop smoking in next 12 months 46Made an attempt to stop in a given year 30Used medication to aid cessation in a given year* 8Attended smokers clinic or followed behaviouralsupport programme†

2

*Based on surveys showing that 30% of smokers make a quit attempt each yearand that in 25% of quit attempts medication is used.†Based on figures from attendance in 2001 at NHS cessation clinics.

No/YesDo you want to stop smoking for good?

No/YesAre you interested in making a serious attempt to stop in the near future?

No/YesAre you interested in receiving help with your quit attempt?

Simple qualitative test of motivation to stop smoking. A “yes” response to allquestions suggests that behavioural support and/or medication should beoffered

Smoking

Not smoking

Not thinkingabout stopping

Contemplatingstopping

Stayingstopped

Attemptingto stop

Preparingto stop

Relaspingback to

smoking

Stages of change in process of stopping smoking. Adapted from Prochaskaet al. Clin Chest Med 1991;12:727-35

Key pointsx Motivation to stop smoking can be assessed with simple questionsx Once a decision to quit is made, success is determined more by the

degree of dependence than the level of motivationx Simple questions can identify heavily dependent smokersx For high dependence, higher strength nicotine products may help

Further readingx Kozlowski LT, Porter CQ, Orleans CT, Pope MA, Heatherton T.

Predicting smoking cessation with self-reported measures ofnicotine dependence: FTQ, FTND, and HSI. Drug Alcohol Depend1994;34:211-6.

x National Institute for Clinical Excellence. Technology appraisalguidance No 38. Nicotine replacement therapy (NRT) and bupropion forsmoking cessation. London: NICE, 2002.

x Sutton S. Back to the drawing board? A review of applications ofthe transtheoretical model to substance use. Addiction2001;96:175-86.

Competing interests: RW has done paid research and consultancy for,and received travel funds and hospitality from, manufacturers ofsmoking cessation products, including nicotine replacement therapiesand Zyban. See chapter 1 for the series editor’s competing interests.

ABC of Smoking Cessation

8

4 Use of simple advice and behavioural supportTim Coleman

The most effective methods of helping smokers to quit smokingcombine pharmacotherapy (such as nicotine or bupropion)with advice and behavioural support. These two componentscontribute about equally to the success of the intervention.Doctors and other health professionals should therefore befamiliar with what these strategies offer, encourage smokers touse them, and be able at least to provide simple advice andbehavioural support to smokers. They also need to be familiarwith other sources of support, such as written materials,telephone helplines, and strategies for preventing relapses. Thischapter focuses on non-pharmacological interventions.

Brief adviceThe Cochrane Tobacco Addiction Group defines brief adviceagainst smoking as “verbal instructions to stop smoking with orwithout added information about the harmful effects ofsmoking.” All the published guidelines on managing smokingcessation recommend that all health professionals should givesimple brief advice routinely to all smokers whom theyencounter. The success rate of brief advice is modest, achievingcessation in about 1 in 40 smokers, but brief advice is one of themost cost effective interventions in medicine. The previousarticle in this series gave tips on how to take account ofsmokers’ motivation to stop, but the key point is that only oneor two minutes are needed for effective brief advice to bedelivered in routine consultations.

Advice along these lines is probably most effective insmokers with established smoking related disease. It is alsomore effective if more time is spent discussing smoking andcessation and if a follow up visit is arranged to review progress.More intensive advice (taking more than 20 minutes at theinitial consultation), inclusion of additional methods ofreinforcing advice (such as self help manuals, videos, or CDRoms and showing smokers’ their exhaled carbon monoxidelevels), and follow up can increase success rates by a factor of1.4. Again, the cost effectiveness of these more intensiveinterventions is extremely high—higher than many of theinterventions provided routinely in primary or secondary care.The case is therefore strong to integrate simple advice into allhealth consultations with smokers and to offer more intensiveadvice and follow up to smokers who are motivated to quit.

Behavioural supportIntensive behavioural support provided outside routine clinicalcare by appropriately trained smoking cessation counsellors isthe most effective non-pharmacological intervention forsmokers who are strongly motivated to quit. Meta-analyses oftrials have shown that about 1 in 13 smokers who are motivatedenough to attend individual counselling from a smokingcessation counsellor are likely to quit as a result of this. Differentapproaches to counselling based on various psychologicalmodels have been studied, but no one type of intensivebehavioural support is clearly more effective than any other.Behavioural support usually involves a review of patients’smoking histories and their motivation to quit, with smokersbeing helped to identify situations where they might have a

Suggested phrasing for giving brief advice to smokersx “The best thing you can do for your health is to stop smoking, and I

would advise you to stop as soon as possible.”x “Tobacco is very addictive, so it can be very difficult to give up, and

many people have to try several times before they succeed. Yourchances of succeeding are much greater if you make use ofcounselling support, which I can arrange for you, and eithernicotine replacement therapy or the antismoking drug Zyban[bupropion], which I can prescribe for you if you wish.”

x “If you are ready to try to give up smoking now, then the best thingis to see a counsellor as soon as possible, and I can arrange that foryou. If not, then I’d like you to take home this leaflet and read it, orring the NHS smokers’ helpline, to get further information.”

x “The best thing is to get counselling from experts, but if this isn’tpossible, you should make sure that you have good information onthe health effects of smoking and some tips on ways of stoppingsmoking and that you know where to turn for further help andsupport.”

x “How do you feel about your smoking?”x “How do you feel about tackling your smoking now?”

Disc

ount

ed c

ost p

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ear o

f life

sav

ed (£

)

Pravas

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ry pre

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n of

cardio

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Aspir

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5000

10 000

15 000

20 000

25 000

Cost effectiveness of brief advice versus common medical interventions

Measuring the level of carbon monoxide in smokers’exhaled air can motivate them to quit or be a usefultool in monitoring their progress with cessation

9

high risk of relapsing during a quit attempt; counsellors alsoencourage smokers to develop problem based strategies fordealing with these situations.

Intensive behavioural support is equally effective whetherfor an individual or on a group basis, but the latter is more costeffective (although not all smokers are willing to take part in agroup). Moreover, in a group, smokers gain mutual supportfrom other smokers who are trying to quit. Sessions aregenerally smoker oriented, and group facilitators, who manage20 to 25 smokers simultaneously, ensure that smokers’ keyconcerns about quitting are tackled.

Who should deliver theseinterventions?All doctors and other health professionals should provide briefadvice as a low intensity but routine intervention to all smokerswho use their services. For smokers who do not wish to take upintensive behavioural support, doctors or other professionalsshould, where possible, also provide advice and follow up inprimary and secondary care services; this should be providedeither directly by the primary or secondary care clinician or byarrangement with another healthcare professional. Intensivesupport services need to be available to all smokers by referral.How to organise and deliver these services is discussed later inthis series.

In the United Kingdom, smoking cessation services havenow been established as part of a national initiative, and allhealth professionals should be able to refer smokers forbehavioural support from a person who has specifically trainedfor this role. Any interested, trained health professional can bean effective smoking cessation counsellor, and those workingfor smoking cessation services in England come from variedclinical and non-clinical backgrounds.

Written self help materials andhelplinesSelf help materials that aim to promote smoking cessation aredefined by the Cochrane Collaboration as “structuredprogramming for smokers trying to quit without intensivecontact from a therapist.” This definition includes writtenleaflets, videos, and CD Roms. Giving smokers self helpmaterials is more effective than doing nothing but is not aseffective as simple advice. The effectiveness of self helpmaterials may be improved by tailoring them to individualsmokers’ needs. Telephone helplines are widely available andprovide a simple alternative means of providing low costcounselling or advice to motivated smokers, although they arealso less effective than face to face advice from a healthprofessional.

Complementary therapiesComplementary therapies have been advocated by some aseffective cessation interventions, but little evidence exists tosupport their use. Acupuncture and related therapies such asacupressure have been found to be no more effective thanplacebo therapies. Similarly, although hypnotherapy is alsoprovided in the belief that it can weaken the desire to smoke orcan strengthen the will to stop, no convincing evidence existsthat it works. Designing placebo care for randomised, controlledtrials of complementary therapies is challenging, but withoutsuch trials no conclusions can be reached about the utility ofcomplementary therapies in smoking cessation.

Strategies used in intensive behavioural supportx Review smoking history—number smoked per day, time of first

cigarette in the day. Ask smoker to keep diary of activities thatcoincide with smoking

x Review smoking behaviour—past quit attempts, what helped, andreasons for failure

x Emphasise need for total abstinencex Emphasise need to combat psychological and physical nicotine

addiction, where appropriatex Identify triggers to smoking and encourage smoker to develop

strategies for countering these (for example, avoid places oractivities associated with smoking)

x If relevant, encourage smoker to develop strategies for avoidingrelapse when drinking alcohol

x Encourage appropriate action: set quit date, inform or enlistsupport of peer group or family, and prescribe nicotine addictiontreatment

x Follow up to review progress and prescribe or issue nicotineaddiction treatment

Written leaflets can also help people to stop smoking

Websites giving quitline informationx http://cancercontrol.cancer.gov/tcrb/quitlines.html (United States)x www.ash.org.uk/html/quit/givingup.html (for guide to UK quitlines)x www.asianquitline.org (UK, for Asians)x www.quitnow.info.au/quitlineinfo.html (Australia)x www.quit.org.nz (New Zealand)

Adequate training in smoking cessationcounselling is much more importantthan the discipline of the healthprofessional providing that support

The challenge for those who advocate complementarytherapies in smoking cessation is to provide evidence fortheir effectiveness

ABC of Smoking Cessation

10

Prevention of relapseMost smokers who are trying to stop make several quit attemptsbefore they succeed. Consequently, smokers have frequentlybeen provided with treatments that health professionals believewill help smokers to sustain quit attempts and will help toprevent relapse. Recent American guidelines on smokingcessation recommended that when clinicians encounter apatient who has recently quit smoking they should reinforce thepatient’s decision to quit and help the patient to resolve anyresidual problems.

Combination with pharmacotherapyAll the evidence on the combination of non-pharmacologicaland pharmacological interventions indicates that the effectsmultiply rather than add together. Therefore the effectiveness ofall non-pharmacological therapy is increased substantially bypharmacotherapy, and the more intensive thenon-pharmacological support, the greater the extent of thatincrease. It is therefore important that non-pharmacologicalinterventions are recognised as equal contributors to the overallsuccess of smoking cessation interventions, which can achieveup to 20% success with any quit attempt, and that they are notdiscarded as inferior or irrelevant alternatives to drugtreatment. The provision of non-pharmacological interventions,ranging from simple advice to intensive behavioural support,needs to become a routine component of healthcare delivery tosmokers.

Competing interests: TC has been paid for speaking at a conference byGlaxoSmithKline, a drug company that manufactures treatments fornicotine addiction; he has also done consultancy work on one occasion forPharmacia. See chapter 1 for the series editor’s competing interests.

% o

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Inten

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GP pl

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3

6

9

12

15

Comparison of effective smoking cessation interventions: percentage ofsmokers who quit as a result of the intervention. Adapted from Raw et al.Thorax. 1998;53(suppl 5, part 1):S1-19

Key pointsx Simple advice to give up smoking is one of the most cost effective

interventions in medicinex Doctors and other health professionals should routinely give brief,

non-judgmental advice to stop smoking to all smokers they seex Self help materials such as leaflets, videos, or helplines provide

additional supportx Intensive behavioural support from a trained counsellor is the most

effective non-drug treatment for smokersx Behavioural support is equally effective for groups and individualsx The most effective interventions combine behavioural support with

drug treatmentx Therapy that combines drug treatment with the level of behavioural

support most acceptable to the smoker should be routinelyavailable to all smokers

Further readingx Silagy C, Stead LF. Physician advice for smoking cessation. Cochrane

Database Syst Rev 2003;(2):CD000165.x Lancaster T, Stead LF. Individual behavioural counselling for

smoking cessation. Cochrane Database Syst Rev 2003;(2):CD001292.x Lancaster T, Stead LF. Self-help interventions for smoking

cessation. Cochrane Database Syst Rev 2003;(2):CD001118.x Stead LF, Lancaster T. Group behaviour therapy programmes for

smoking cessation. Cochrane Database Syst Rev 2003;(2):CD001007.x Stead LF, Lancaster T, Perera R. Telephone counselling for smoking

cessation. Cochrane Database Syst Rev 2003;(2):CD002850.

Use of simple advice and behavioural support

11

5 Nicotine replacement therapyAndrew Molyneux

Although products for nicotine replacement therapy (NRT)have been available for over 20 years, they have been excludeduntil recently from state or insurance based health serviceprovision in the United Kingdom and many other countries.They have therefore not been widely prescribed by doctors whohelp smokers wanting to quit. Recent changes in funding policyin the United Kingdom and new guidance from the NationalInstitute for Clinical Excellence (which covers England andWales) mean that NRT products can and should now be madeavailable to all smokers who want to stop smoking.Like other pharmacological interventions for helping smokersto quit (see the next chapter), NRT is most effective when usedin conjunction with behavioural and other types ofnon-pharmacological cessation interventions.

Mechanism of actionThe main mode of action of NRT is thought to be thestimulation of nicotinic receptors in the ventral tegmental areaof the brain and the consequent release of dopamine in thenucleus accumbens. This and other peripheral actions ofnicotine lead to a reduction in nicotine withdrawal symptoms inregular smokers who abstain from smoking.

NRT may also provide a coping mechanism, makingcigarettes less rewarding to smoke. It does not completelyeliminate the symptoms of withdrawal, however, possibly becausenone of the available nicotine delivery systems reproduce therapid and high levels of arterial nicotine achieved when cigarettesmoke is inhaled.

All the available medicinal nicotine products rely onsystemic venous absorption and do not therefore achieve suchrapid systemic arterial delivery. It takes a few seconds for highdoses of nicotine from a cigarette to reach the brain; medicinalproducts achieve lower levels over a period of minutes (for nasalspray or oral products such as gum, inhalator, sublingual tablet,or lozenge) and hours (for transdermal patches).

Evidence for effectivenessThe most recent Cochrane reviews suggest that NRT leads to anear doubling of cessation rates achieved bynon-pharmacological intervention, irrespective of the level ofthat intervention.

NRT will therefore increase the chance of success with anyquit attempt but is most effective when combined with intensivebehavioural support.

No evidence exists that NRT is any more or less effective inany specific subgroups of smokers, such as those in hospital orpresenting with a smoking related disease. The effectiveness ofNRT in adolescents and children who smoke has not beenestablished, though studies are in progress.

Who should receive NRT?Nicotine replacement therapy, preferably in conjunction withbehavioural support (see the previous chapter), shouldgenerally be offered to any regular cigarette smoker

Plas

ma

nico

tine

conc

entra

tion

(ng/

ml)

0

10

15

20

5

0

20

40

60

80

100

Cigarette(nicotine delivery, 1-2 mg)

Cigarette(nicotine delivery, 1-2 mg), arterial

Plas

ma

nico

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conc

entra

tion

(ng/

ml)

0

10

15

20

5

Oral snuff

Minutes

Plas

ma

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conc

entra

tion

(ng/

ml)

0 30 60 90 1200

10

15

20

5

Gum(nicotine delivery, 4 mg)

0Spray

0

10

15

20

5

Nasal spray(nicotine delivery, 1 mg)

Minutes

0 30 60 90 120 1600

10

15

20

5

Transdermal patch(nicotine delivery, 15 mg)

Rise in blood nicotine concentrations after smoking a cigarette and afterusing different NRT products (after overnight abstinence from cigarettes).Values are for venous blood, except where shown. Adapted fromHenningfield JE. N Engl J Med 1995;333:1196-203

Proportion of smokers abstaining from smoking long term,by cessation intervention. Adapted from West et al, 2000*

InterventionLong term

abstinence (%)No intervention (willpower alone) 3Brief, opportunistic advice from doctor to stop 5

Plus NRT 10Intensive support from specialist 10

Plus NRT 18

*See Further Reading box

This article outlines the mechanism of action of nicotinereplacement therapy (NRT), the evidence for itseffectiveness, and how and when NRT products canbe used

12

prepared to make a quit attempt. NRT is relatively unlikely tohelp smokers who are not motivated to quit or do notexperience or expect to experience nicotine withdrawalsymptoms. Any healthcare professionals can assess thesecharacteristics in the following ways:x Motivation to quit: smokers should be asked whether theywould like to stop smoking. Those willing to stop within thenext 30 days should set a quit date and their dependenceshould be assessed.x Dependence: smokers should be asked whether they havetried to quit smoking before, whether they experiencedsymptoms of nicotine withdrawal, and whether they anticipatethese symptoms in a future quit attempt.

Formulations and use of NRTSix NRT formulations are currently available. In the UnitedKingdom, all of these are now available on prescription throughthe NHS and most can also be bought over the counter atpharmacies. In addition, patch, gum, and lozenge formulationsare on general sale in supermarkets and other outlets. As littleevidence exists that any one of these formulations is moreeffective than any other or that any is more effective inparticular subgroups of smokers, the choice of product shouldgenerally be guided by the smoker’s preference and clinicalconsiderations relating to duration of action.

Evidence exists, however, that higher dose gum is moreeffective than lower dose gum in those smoking 20 or morecigarettes a day, that higher dose patches are more effectivethan low dose patches in those smoking more than 10cigarettes a day, and that combining products (such as patchand nasal spray, or patch and inhalator) is more effective thanusing single agents alone. NRT, and nicotine gum in particular,has also been shown to help to control the weight gaincommonly experienced after cessation.

NRT should be prescribed in blocks, usually of two weeks, becontinued in those maintaining abstinence from cigarettes for atotal of six to eight weeks, and then discontinued. If possible,NRT prescriptions should be linked to the delivery of follow upbehavioural support. The prescriptions can be issued throughdelegated prescribing by nurses or other health professionals.

No evidence shows that gradual withdrawal of NRT is betterthan abrupt withdrawal. The risk of dependence on NRT issmall, and only a small minority of patients (about 5%) who quitsuccessfully continue to use medicinal nicotine regularly in thelonger term.

Studies investigating the use of NRT to help smokers toabstain from smoking for certain periods (for example, at workor in a public place) or to reduce the number of cigarettes theysmoke each day are in progress.

Safety of NRTObtaining nicotine from NRT is considerably safer than doingso from cigarettes, as the patient is not exposed to any of themany harmful products of tobacco combustion.

Long term use of NRT is not thought to be associated withany serious harmful effects. Concerns over the safety of NRT incircumstances in which nicotine might be harmful—such as inpregnancy, cardiovascular disease, or in adolescents—thereforeneed to be considered in relation to the safety of the likelyalternative, which is continued intake of nicotine fromcigarettes.

Offer nicotine replacement therapy

No

No

Yes

Yes

Assess motivation to quit:is smoker willing to stop in next 30 days?

Give clear adviceto stop smoking

Assess dependency on nicotine: past or anticipatedwithdrawal symptoms (craving for cigarettes, irritability,aggression, anxiety, depression, poor concentration)?

Help smoker tostop smoking

Decision pathway for giving nicotine replacement therapy

NRT formulations and their availabilityTransdermal patch—On general sale,* at pharmacies, and on

prescriptionGum—On general sale,* at pharmacies, and on prescriptionNasal spray—At pharmacies and on prescriptionInhaler—At pharmacies and on prescriptionSublingual tablet—At pharmacies and on prescriptionLozenge—On general sale,* at pharmacies, and on prescription*In supermarkets and other outlets

Nicotine gum products

Prescribing details for NRT formulations

Formulation (dose) UsePatch (16 h patch: 15, 10, or 5 mg;24 patch: 21, 14, or 7 mg)

One daily on clean, unbrokenskin; remove before bed (16 hpatch) or next morning (24 h);new patch, fresh site

Gum (2 or 4 mg per piece) Chew gum until taste is strong,then rest gum between gum andcheek; chew again when taste hasfaded

Inhalator (10 mg per cartridge) Inhale as requiredSublingual tablet (2 or 4 mgper piece)

Rest under tongue until dissolved

Lozenge (1, 2, or 4 mg per piece) Place between gum and cheekand allow to dissolve

Nasal spray (10 mg/ml, 0.5 mgper spray)

One spray each nostril asrequired

Side effects for all formulations: sore throat, hiccups, indigestion, nausea,headache, palpitations (but without hiccups for the inhalator and plus itching,erythma, and rash for patches).

Smokers should be advised not to smoke while usingNRT products

Nicotine replacement therapy

13

Pregnancy and breast feedingSmoking during and after pregnancy poses a serious risk to thehealth of both mother and baby. NRT may also have adverseeffects on placental function and fetal development, butalthough the magnitude of these pure nicotine effects inhumans is uncertain, the likelihood is that obtaining nicotinefrom cigarette smoke is far more harmful.

Complete avoidance of all nicotine should therefore be theobjective in pregnancy and breast feeding, and 30% of pregnantwomen succeed in stopping smoking during pregnancy withoutpharmacological support. However, for those who do notsucceed, or have previously failed in an attempt to quit, the useof NRT to support smoking cessation in pregnancy is justifiablein relation to the risk of continued smoking. Pregnant or breastfeeding women who make an informed choice to try NRTshould probably be advised to use shorter acting products tominimise fetal exposure to nicotine overnight.

Cardiovascular diseaseNicotine replacement therapy is safe in smokers with stablecardiovascular disease. In acute cardiovascular conditions, suchas unstable angina, acute myocardial infarction, or stroke, NRTshould be used with caution because nicotine is avasoconstrictor. However, as medicinal nicotine is unlikely to bemore harmful in this context than continued intake of nicotine(and the associated tar, carbon monoxide, and other products)from cigarettes, it is appropriate to offer NRT to help insmoking cessation in patients with acute cardiovascular diseasewho continue to smoke. In these circumstances it is probablyadvisable to use rapidly reversible preparations—such as gum,inhalator, nasal spray, or lozenge—as absorption of nicotineceases when the product is withdrawn; after removal of atransdermal patch, however, the skin can continue to absorbnicotine slowly from the skin for some time.

Young smokersMost adult smokers established their smoking habit as children.Even in adolescence, many smokers are addicted to nicotine andwould like to stop smoking. Over two thirds of adolescentsmokers have tried to stop, and failed. Although no randomisedcontrolled trials of the effectiveness of NRT in young smokershave been published, several NRT products are licensed for use insmokers aged under 18, on medical advice. In addition, the recentNational Institute for Clinical Excellence guidance on NRTsuggests that smokers under 18 who want to quit using NRTshould discuss this with a relevant healthcare professional. Untilfurther evidence arises to the contrary, it therefore seemsreasonable to use NRT in adolescent smokers who are motivatedto quit and show evidence of nicotine dependence.

Competing interests: AM has received research funding and beenreimbursed for attending conferences by Pharmacia, a manufacturer ofNRT. He has also received speaking fees and been reimbursed forattending a conference by GlaxoSmithKline, which manufacturesbupropion and NRT. See chapter 1 for the series editor’s competinginterests.

Key pointsx Nicotine replacement therapy is an effective aid to smoking

cessationx Smokers who are motivated to quit and are dependent on nicotine

should be offered NRTx The choice of NRT product should normally be guided by the

patient’s preferencex NRT should be prescribed for six to eight weeks, in blocks of up to

two weeks, contingent on continued abstinencex Obtaining nicotine from NRT is considerably safer than smokingx NRT is safe in stable cardiac disease, but caution is needed in

unstable, acute cardiovascular disease, pregnancy, or breast feeding,or in those aged under 18

Further readingx Silagy C, Mant D, Fowler G, Lancaster T. Nicotine replacement

therapy for smoking cessation. Cochrane Database Syst Rev2000;CD000146.

x Tobacco Advisory Group of the Royal College of Physicians.Nicotine addiction in Britain. RCP: London, 2000.

x West R, McNeill A, Raw M. Smoking cessation guidelines for healthprofessionals: an update. Thorax 2000;55:987-99.

x Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Fox BJ, GoldsteinMG, et al. A clinical practice guideline for treating tobacco use anddependence. JAMA 2000;283:3244-54.

The photo of the pregnant woman is with permission fromFaye Norman/SPL.

ABC of Smoking Cessation

14

6 Bupropion and other non-nicotinepharmacotherapiesElin Roddy

Although nicotine replacement has been the first line drugtreatment for smoking cessation for many years, other drugs ofproved efficacy are also now available. Foremost among these isbupropion (marketed as Zyban). Bupropion was developed andinitially introduced in the United States as an antidepressant butwas subsequently noted to reduce the desire to smoke cigarettesand shown in clinical trials to be effective in smoking cessation.

Mechanism of actionBupropion is an atypical antidepressant structurally similar todiethylpropion, an appetite suppressant. The mechanism of theantidepressant effect of bupropion is not fully understood, butbupropion inhibits reuptake of dopamine, noradrenaline, andserotonin in the central nervous system, is a non-competitivenicotine receptor antagonist, and at high concentrations inhibitsthe firing of noradrenergic neurons in the locus caeruleus.

It is not clear which of these effects accounts for theantismoking activity of the drug, but inhibition of the reductionsin levels of dopamine and noradrenaline levels in the centralnervous system that occur in nicotine withdrawal is likely to beimportant. The antismoking effect of bupropion does not seemto be related to the antidepressant effect as bupropion is equallyeffective as a smoking cessation therapy in smokers with andwithout depression.

Evidence for effectivenessWhen given in association with intensive behavioural support,bupropion is as effective as nicotine replacement therapy(NRT), and like NRT, leads to a near doubling of the smokingcessation rate, achieving long term abstinence in 19% ofsmokers who use it to quit.

The effectiveness of bupropion in conjunction with lessintensive levels of behavioural support has not been tested inclinical trials. Like NRT, however, bupropion therapy probablyincreases the chance of success with any quit attempt but ismost effective when combined with intensive behaviouralsupport. No evidence suggests that bupropion is any more orless effective in any specific subgroups of smokers, such as thosein hospital or those with a smoking related disease.

Bupropion also seems to attenuate the weight gain thatoften occurs after quitting. More prolonged use of bupropion(beyond the recommended eight weeks) seems to confer furtherprotection against relapse.

Using bupropionDoseBupropion is marketed in the United Kingdom as an oralprolonged release 150 mg tablet. An eight week course oftreatment is recommended and costs about £86 ($143; €123).Smokers should start taking bupropion one week before theirintended quit date. A reduced dose—that is, one tablet daily—isrecommended in elderly people and those with liver or renalimpairment.

Dopaminereuptakeinhibition

Corpuscallosum

Non-competitivenicotine

antagonist

Noradrenergicinhibition

Serotoninreuptakeinhibition

Ventraltegmentalarea

Raphénuclei

Pedunculo-pontinenucleus

Central nucleusof the amygdala

Hippocampus

Bed nucleus ofstria terminalis

Nucleusaccumbens

shell

Prefrontalcortex

Effects of bupropion on the central nervous system

Week

Abst

inen

ce ra

te (%

of p

atie

nts)

1 2

Quit day (day 8 of treatment)

3 4 5 6 7 8 9

End oftreatment

10 11 12 26 520

20

40

60

80

100Placebo (n=160)

Nicotine patch (n=244)

Bupropion (n=244)

Bupropion and nicotine patch (n=245)

Abstinence from smoking in relation to sustained release bupropion ornicotine patch, or both. Adapted from Jorenby et al. N Engl J Med1999;340:685-91

Week 1

Weeks 2-8

Days 6-7: 150 mg twice daily

150 mg twice daily

Days 1-6: 150 mg once daily

Quit smoking between day 7and day 14 of treatment

Dose regimen for bupropion

Bupropion is the only non-nicotine drug licensed for usein smoking cessation in the United Kingdom and theEuropean Union; it became available for use in 2000

15

Unwanted effectsThe most serious adverse effect of bupropion is seizure, whichaffects an estimated 1 in 1000 users. More common side effectsinclude dry mouth, insomnia, skin rash, pruritus, andhypersensitivity. Rarely the drug may cause a reactionresembling serum sickness.

Contraindications and precautionsBupropion is contraindicated in patients with current or pastepilepsy. It should also be used with extreme caution in patientswith conditions predisposing to a low threshold for seizure—history of head trauma, alcohol misuse, diabetes treated withhypoglycaemic agents or insulin—and in patients taking drugsthat lower the seizure threshold (for example, theophylline,antipsychotics, antidepressants, and systemic corticosteroids).

Bupropion is also contraindicated in patients with a historyof anorexia nervosa and bulimia, severe hepatic necrosis, orbipolar disorder.

Pharmacokinetics and interactionsBupropion reaches a peak plasma concentration three hoursafter oral administration, with steady state concentrationreached within eight days. It has a half life of 20 hours and ismetabolised in the liver by cytochrome p450.

Use with NRTOne study has suggested that combined nicotine patch therapyand bupropion may produce higher quit rates than nicotinepatches alone. Combination therapy may therefore berecommended to patients attending specialist cessation clinicswho find it difficult to quit using a single pharmacotherapy.Monitoring for hypertension is recommended when combinedtherapy is used.

Special groupsChronic obstructive pulmonary disease—Smoking cessation is

the most important intervention in this disease. Bupropion hasbeen shown to be effective and well tolerated in this group ofpatients.

Ischaemic heart disease—Smoking cessation is one of the mostimportant interventions in this disease. Bupropion is notcontraindicated or subject to caution except in diabetic patientstreated with hypoglycaemic agents or insulin (caution) or inpatients taking propafenone or flecainide (dose reduction ofantiarrhythmics advised).

Power of the pressx The use of bupropion has been inhibited in the United Kingdom

by a series of articles in national newspapers soon after the drugwas launched

x These implicated bupropion in some serious adverse effects,including death, in a number of cases

x Post-marketing surveillance has since shown that serious adverseevents are rare with bupropion, occurring at about half the averagereported rate for new drugs in Britain

Study week

% o

f pat

ient

s ab

stai

ning

5 6 7 10 12 260

10

15

20

25

30

35

5Bupropion

Placebo

Long term abstinence from smoking in patients with chronic obstructivepulmonary disease, after treatment with bupropion. Adapted from Tashkinet al. Lancet 2001;357:1571-5

Bupropion should not be used with a monoamine oxidaseinhibitor, and at least 14 days should elapse betweenstopping such treatment and starting bupropion

Bupropion interacts with a number of commonly useddrugs, including some antidepressants, type 1cantiarrhythmics, and antipsychotics

Interactions of bupropion

Drug Mechanism of interaction Action requiredAntidepressants (desipramine, fluoxetine)

Prolongs action of drugs metabolised bycytochrome p450 (CTP2D6)

Start these drugs at low end of dose range in patientsalready taking bupropion. Decrease dose of ongoingtreatment with these drugs if patient starts bupropion

Antipsychotics (risperidone, thioridazine)Type 1c antiarrhythmics (propafenone,flecainide)� blockers (metoprolol)Antiepileptics (carbamazepine,phenobarbitone, phenytoin) Metabolism of bupropion induced Bupropion dose increase not recommended*

Levodopa Limited clinical data suggest higherincidence of adverse eventsGive bupropion with caution to patients receivinglevodopa

MAOIs (including moclobemide) Avoid using bupropion for two weeks after MAOIs

Ritonavir Increased plasma bupropionconcentration; risk of increased toxicity Avoid concomitant use

MAOI = mono amine oxidase inhibitor.*Bupropion contraindicated in epilepsy.

ABC of Smoking Cessation

16

Pregnant women—No trials of bupropion have been done inpregnant women. Bupropion is therefore not recommended foruse in pregnancy.

Other antidepressantsNortriptyline, a tricyclic antidepressant with mostlynoradrenergic properties and a small amount of dopaminergicactivity, is also effective in cessation therapy, and although fewclinical trials have been done, these suggest an effect of similarmagnitude to that of bupropion. Again, this effect seems to beindependent of the presence of depressive symptoms.

Several other antidepressants have been used in smokingcessation including imipramine, doxepin, venlafaxine,fluoxetine, and the reversible monoamine oxidase inhibitormoclobemide. The latter may be effective in some patients, butthe effectiveness of other therapies is unproved.

Other pharmacotherapiesClonidine is an � noradrenergic agonist that suppresses

sympathetic activity and has been used for hypertension and toreduce withdrawal symptoms associated with misuse of alcoholand opiates. Both in its oral and low dose patch formulation,clonidine increased smoking cessation in eight out of nine trials,but the drug is associated with serious side effects, includingsedation and postural hypotension. Clonidine is thereforeprobably best reserved for smokers who cannot or do not wishto use NRT, bupropion, or nortriptyline.

Mecamylamine is a nicotinic antagonist originally used todecrease cholinergic activity and thus reduce blood pressure. Itblocks the effects of nicotine but does not precipitatewithdrawal symptoms. Two trials have suggested that a low dosemecamylamine patch combined with a nicotine patch wassuperior to placebo, but a recent multicentre trial has failed toshow efficacy.

Sensory replacement therapy could be useful for the manysmokers who report missing the sensory aspects of smoking.Sensory effects of smoking are important in reinforcingsmoking behaviour, and loss of these effects may contribute torelapse. Two inhalers containing ascorbic acid or citric acid havebeen tested, and both increased rates of short term cessation.Further testing of these adjuncts to NRT or other non-nicotinetherapies is warranted, but neither of these treatments iscurrently used routinely in specialist cessation clinics.Competing interests: ER has been reimbursed by GlaxoSmithKline, themanufacturer of bupropion, for attending one international meeting andhas attended educational events sponsored by Pharmacia, themanufacturer of Nicorette. See chapter 1 for the series editor’s competinginterests.

Non-nicotine therapies for smoking cessationProved effective—Bupropion, clonidine, nortriptylinePossibly effective—Noradrenergic antidepressants, monoamine oxidase

inhibitors, mecamylamine plus nicotine replacement therapy,sensory replacement

Ineffective or insufficient evidence—Anorectics, benzodiazepines,� blockers, buspirone, caffeine, ephedrine, cimetidine, dextrose,lobeline, naltrexone, ondansetron, phenylpropanolamine, silveracetate, stimulants, selective serotonin reuptake inhibitors

Key pointsx NRT is the treatment of choice, but non-nicotine drugs are also

available as an alternativex Bupropion is the most commonly used non-nicotine treatmentx Bupropion is generally safe and well toleratedx Bupropion is as effective as NRT and doubles quit rates when given

alongside intensive behavioural supportx Bupropion must not be given to patients at increased risk of

seizuresx Nortriptyline has been less widely studied, but its effectiveness

seems similar to that of bupropionx Any risks associated with these therapies are likely to be much less

serious than the risks from continued smoking

Further readingx Antidepressants for smoking cessation. Cochrane Database Syst Rev

2003;(3):CD000031x Royal College of Physicians of London. Nicotine addiction in Britain.

London: RCP, 2000.x Hurt RD, Sachs DPL, Glover ED, Offord KP, Johnston JA, Dale LC,

et al. A comparison of sustained-release bupropion and placebo forsmoking cessation. N Engl J Med 1997;337:1195-202.

No trials of bupropion have been done in smokers agedunder 18, and the drug is not licensed or recommendedfor smoking cessation in this age group

Elin Roddy is clinical research fellow at the University of Nottinghamin the division of respiratory medicine at City Hospital, Nottingham.

Bupropion and other non-nicotine pharmacotherapies

17

7 Special groups of smokersTim Coleman

Earlier articles in this series have provided general guidance ondelivering smoking cessation interventions. This chapterinvestigates issues relevant to several special groups of smokers.

Pregnant womenIn the United Kingdom over a quarter of pregnant women whosmoke continue to do so during pregnancy. These women tendto be young, single, of lower educational achievement, and inmanual occupations. If they have a partner, their partner is alsomore likely to smoke. Smoking has substantial adverse effectson the unborn child, including growth retardation, pretermbirth, miscarriage, and perinatal mortality. Most of this harm isprobably caused by toxins in cigarette smoke, such as carbonmonoxide, nicotine, cyanide, cadmium, and lead. Nicotine itselfmay cause harm, however, through placental vasoconstrictionand possible developmental effects on the fetus.

Ideally, women should stop smoking before gettingpregnant. In practice, however, few do, and it is pregnancy itselfthat seems to be the key motivator to stop. About a quarter ofwomen who smoke manage to stop for at least part of theirpregnancy, mostly within the first trimester, but most of thesestart smoking again after their child is born.

Most pregnant women (80% in UK surveys) accept thatstopping smoking is the most important lifestyle change thatthey can make during pregnancy, and consequently mostwomen will be receptive to discussion of their smoking and thepossibility of stopping. Those who continue to smoke, however,tend to hold rather different views from those who give up—forexample, only about 30% of those who continue to smokebelieve that smoking during pregnancy is “very dangerous” totheir baby, compared with 80% of those who quit. It is,therefore, particularly important that health professionals tailortheir message to the perceptions and beliefs of smokers indifferent stages of pregnancy.

Evidence based cessation interventions

Behavioural interventionsThe effectiveness of brief interventions by different healthprofessionals is not as clearly established for pregnant smokersas for non-pregnant smokers, but some form of intervention isclearly necessary to prompt cessation. However, intensivecessation programmes delivered to pregnant women byspecially trained staff outside routine antenatal care are ofproved effectiveness in promoting cessation and in reducinglow birth weight and preterm birth.

For every 100 pregnant women who are still smoking at thetime of their booking an antenatal visit, about 10 will stopsmoking with “usual care” and a further six or seven can beencouraged to stop as a result of formal cessation programmes.As the available trials have investigated the effects of variedprogrammes—with few common elements—it is difficult to drawconclusions about which facets of these are effective.

PharmacotherapyIdeally, to minimise potential adverse effects on the fetus,pregnant smokers should give up smoking without resort topharmacotherapy. In practice, however, many do not. Thus, the

Year

% o

f wom

en s

mok

ing

in 1

2 m

onth

sbe

fore

thei

r pre

gnan

cy

1992 1993 1994 1995 1996 1997 1998 19990

10

20

30

40

50

% o

f wom

en w

ho c

ontin

ue to

sm

oke

durin

g pr

egna

ncy

0

10

20

30

40

50