By: Andrea H.
Weinberger, Pamela Walters, Taryn M. Allen, Melissa M. Dudas, Kristi A.
Sacco and Tony P. George
Nicotine dependence is found in at least a billion people worldwide and in millions in the United States and Great Britain. It is a major cause of morbidity and mortality in all countries, and both active smoking and exposure to passive smoke has significant health care consequences.
Nicotine dependence is found in at least a billion people worldwide and in millions in the United States and Great Britain. It is a major cause of morbidity and mortality in all countries, and both active smoking and exposure to passive smoke has significant health care consequences.
There currently are public health campaigns in both the UK and USA to combat smoking,
and laws against smoking in public places are just one, if not one of the most
visible, of the various
public and community campaigns against smoking. While these campaigns are effective,
most smokers wishing to
quit will utilize pharmacological treatments which involve primarily nicotine
replacement therapy
(NRT) or the use of bupropion. Both have substantial evidence as to
effectiveness, though there are other secondary pharmacological treatments that also
are beginning to find
some support such as vareniciline, clonidine and nortriptyline. The NRTs come in various
forms from patches to
nasal sprays to gum, inhalers, and lozenges. All have substantial support for their
effectiveness. Cognitive-behavioural therapies, especially multimodal
interventions that are tailored to the specific patient, have a good
deal of success and support for that success as well. Despite these effective interventions,
smoking remains a major
public health problem.
Introduction
Cigarette smoking is the single largest preventable cause of substantial morbidity and mortality in developed countries. In the United States, approximately 23% of the general population reports cigarette smoking, which is the most common (> 98%) method of tobacco use (Center for Disease Control (CDC), 2002; Giovino, 2002). Approximately 430 000 people in the USA die each year as a result of smoking-attributable medical illnesses such as lung cancer, chronic obstructive pulmonary disease, cardiovascular disease and stroke (Giovino, 2002). It is estimated that 29% of adults in the United Kingdom smoke (Lader & Meltzer, 2000). This equates to approximately 16 million British smokers. Worldwide, it is estimated that approximately 1.1 billion people use tobacco on a regular basis (CDC, 2002).
In the UK, the proportions of men and women who currently smoke are similar.
Over the past 5 years the overall proportion of
smokers in the UK population has stabilized, although in some groups, such as
adolescents, there has been an
increase. It is thought around 25% of 15-year-olds are regular smokers (NICE, 2002; Lader
& Meltzer, 2000). As a
result of the implementation of tobacco control policies in the USA (e.g. tobacco
excise taxes, advertising
health dangers), the prevalence of cigarette smoking was reduced from 45% in
the 1960s to about 22.9% in 2002 (CDC, 2002). However, it appears that
many of
these remaining smokers have more difficulty quitting smoking, and today’s smoker
has often failed multiple quit attempts despite using behavioural therapies
combined with pharmacological interventions such as nicotine replacement
therapies (NRTs) and sustained-release bupropion. In fact, quit rates with NRTs over the past
15 years
in controlled clinical trials appear to be declining (Irvin et
al., 2003). The remaining population of
smokers has
characteristics associated with smoking persistence and quit attempt failures such
as lower education attainment, less interest in behavioural treatments to
assist with cessation,
and medical, substance abuse and psychiatric co-morbidities (Hughes, 1996b).
In addition, women are smoking at higher rates than in the past, may have
more intense
nicotine withdrawal and depressed mood during quit attempts than men (Gritz et
al., 1996), and may be less responsive to quitting with
NRTs (Perkins et al.,
1999).
Smokers who have failed initial quit attempts generally embrace pharmacotherapies, and given that a large proportion of remaining smokers do not respond to conventional pharmacotherapies, the development of novel and more effective medication treatment for smoking cessation is critical in our efforts to treat nicotine dependence.
Smokers who have failed initial quit attempts generally embrace pharmacotherapies, and given that a large proportion of remaining smokers do not respond to conventional pharmacotherapies, the development of novel and more effective medication treatment for smoking cessation is critical in our efforts to treat nicotine dependence.
Recent advances in our
understanding of nicotine’s effects on central neurotransmitter systems are
guiding basic
and clinical pharmacologists to develop medications for new pharmacological
targets to treat nicotine dependence.
The hazards of smoking are important and well established.
Smokers have a larger number of chronic respiratory diseases and have a
substantially higher risk of cancers and cardiovascular disease. They are twice as likely as
nonsmokers to suffer from fatal ischemic heart disease and four times as likely to suffer
a fatal aortic aneurysm (Parrott et
al., 1998). The National Institute for
Clinical Excellence
(NICE) has estimated that treatment for smoking related disease cost the
National Health Service (UK) around £1.5 billion (Edwards, 2004).
Nicotine addiction is closely linked to socio-economic disadvantage. Smoking
prevalence is higher and nicotine use heavier amongst
poorer smokers. The socio-economic gradient in smoking behaviour accounts for about two-thirds
of the excess premature mortality associated with deprivation.
Smoking is now increasing rapidly throughout the developing
world, and it is estimated that current cigarette smoking will cause about
450 million deaths worldwide in the next 50 years. Reducing current smoking by 50% would prevent 20–30
million premature deaths in the first quarter of this century and 150 million in the second quarter (Doll et
al., 1994). For most smokers, quitting is the single most important
thing they can do to improve their health.
Clinical features of nicotine dependence
Most tobacco users (> 98%) are smokers of cigarettes, and while there are a subset of cigarette smokers who do not smoke every day, most cigarette smokers are daily users and have some degree of physiological dependence on nicotine (Rigotti, 2002). Determination of nicotine dependence is typically accomplished clinically by historical documentation of daily smoking (typically 10–40 cigarettes per day) for several weeks, evidence of tolerance (e.g. lack of aversive effects of nicotine such as nausea and excessive stimulation) and the presence of symptoms of nicotine withdrawal upon smoking cessation. These withdrawal symptoms include dysphoria, anxiety, irritability, decreased heart rate, insomnia (waking in the middle of the night), increased appetite and craving for cigarettes (American Psychiatric Association, 2006). In addition, most dependent smokers state that they smoke their first cigarette of the day within thirty minutes of awakening. Scales such as the Fagerstrom Test for Nicotine Dependence (FTND) allow assessment of the evel of nicotine dependence with scores of 4 on a scale of 0–10 consistent with physiological dependence to nicotine. These scales have been empirically validated (Heatherton et al., 1991).
Interestingly, the positive effects of cigarette smoking
(e.g. taste,
satisfaction) appear to be mediated by non-nicotine components of tobacco such as
tar (Dallery et al.,
2003). Besides
positive reinforcement, withdrawal and craving, there are several secondary
effects of nicotine and tobacco use that may contribute to both maintenance of smoking
and to smoking relapse
including mood modulation (e.g. reduction of negative affect), stress reduction, and
weight control.
In addition, conditioned cues can elicit the urge to smoke even after prolonged
periods of abstinence. Specific effects might be most relevant to individuals high on
dietary restraint
(weight reduction), and psychiatric disorders (mood modulation, stress
reduction). These secondary effects may present additional targets for
pharmacological intervention in certain subgroups of smokers (e.g.
schizophrenic,
depressed, or overweight smokers).
National guidelines
There are clinical practice guidelines available in both the USA and UK. The US Public Health Service published the monograph Treating Tobacco Use and Dependence in 2000 (Fiore et al., 2000), and the American Psychiatric Association recently updated its Practice Guidelines for the treatment of nicotine dependence (APA, 2006). In the UK, a series of guidelines and key documents were published in the late nineties. The paper ‘Smoking kills’ (DOH 98) outlined the government’s plan of action to stop people from smoking. This plan included proposals for abolishing tobacco advertising and promotion. It also looked at ways of altering public attitudes, preventing tobacco smuggling and supporting further research into this important area of public health. Partnerships with other agencies such as businesses were pivotal in order to start the restriction of smoking in public places.
The Royal College of Physicians published smoking cessation guidelines in 1998
which were updated in 2000 (West et
al., 2000). Expert committees such as the Cochrane
Tobacco
Addiction review group were set up to operate in much the same manner as its
American equivalent, The Agency for Health Care Policy Research.
As
a direct result of the change in priority given to the management of smoking,
smoking cessation services were launched in a variety of health action zones throughout England and Wales in
1999–2000. In the 3 years up to and including 2001–2002, £53 million was made available for these services with
further substantial amounts earmarked for the years 2003–2006, £41 million, £46
million and £51 million, respectively. Quarterly reports are fed back to the government
by these services so that progress towards specified targets can be audited.
The government’s guidance on management of smoking cessation is implemented
through The National Institute for Health and Clinical Excellence (NICE). This
organization is part of The National Health Service (NHS) and its role is to
provide guidance for both the NHS and patients on medicines, medical equipment,
and diagnostic tests. It was specifically asked to review the available
evidence on nicotine replacement therapy (NRT) and bupropion and provide guidance
that would inform the NHS about effective evidence-based treatments for smoking
cessation.
Before
we proceed to examine the treatments for smoking, a quick glance at these
official guidelines suggests the manner and context in which, in the UK, smoking cessation treatment should
take place. Nicotine replacement therapy or bupropion should normally only be
prescribed as part of an abstinent contingent treatment (ACT) programme in which the smoker makes a commitment to stop smoking. 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 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. 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. It is thought that there is insufficient
evidence to recommend a combination of bupropion and NRT.
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 consult a health care
professional before either treatment is prescribed. 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.
Conclusions
It is important to identify smoking in health care settings, particularly populations that are high risk for smoking (e.g. individuals with psychiatric and addictive disorders). Identifying and urging people to stop smoking and making sure they are aware of the medical consequences of smoking is important. Many smokers are able to quit with minimal therapeutic interventions. Simple advice to give up smoking is one of the most cost effective interventions we can make in medicine, and yet this is not part of routine health care delivery in many settings both in the US and the UK. Initial attempts to assist individuals with smoking cessation should utilize stepped-care approaches, reserving more intensive behavioural therapies and pharmacological interventions for treatment-resistant smokers. More intensive therapies may be needed for smokers who have had multiple failed quit attempts and smokers with co-morbid psychiatric, alcohol or drug, or medical disorders.
There
are a number of empirically validated pharmacotherapies for the treatment of
nicotine dependence in the USA, including five NRT formulations, varenicline and sustained-release
bupropion, as well as a number of non-approved pharmacotherapies which appear promising. Nicotine replacement
therapy may be the most cost effective, and it is the treatment that has the largest data base supporting
its effectiveness. Bupropion is currently the best non-nicotine treatment, although in a single head-to-head trial,
varenicline was superior to bupropion and to placebo. Intensive behavioral support from a trained counsellor is the
most effective non-drug treatment for smokers, and it appears equally effective
in both an individual and a group setting. Given
that 80% of adult smokers start as teenagers, we should target this age group
in order to have a significant impact on smoking cessation. Little real
research has taken place with this group.
The
issue of passive smoking has received less attention in the UK than in the US
in the past, though the recent ban on smoking in pubs and other public places
reveals that this issue is taking hold in the UK. Efforts need to continue to
be made to make government and business leaders aware of the impact of active
as well as passive smoking on morbidity and mortality.
In
ever increasing pharmacologic dependent societies, additional research on
medications that target neurotransmitter systems involved in nicotine
dependence (e.g. selective GABA and DA receptor agonists) may be important for treatment-resistant
smokers. If people thought that a simple pill with minimal side effects could
help them avoid the discomfort of withdrawal that accompanies smoking
cessation, then perhaps greater progress could be made on this important public
health issue.
References
Peter
Tyrer and Kenneth R. Silk, Cambridge Textbook of Effective Treatments in
Psychiatry, Cambridge University Press 2008.
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