Original articleSmoking cessation: How compelling is the evidence? A review
Introduction
In this review the main focus will be on first-line medications for smoking cessation. It is mainly based on Cochrane meta-analysis and the meta-analysis in the US guidelines updated in 2008. Relevant other papers will be used to illustrate specific areas of clinical importance based on the author's experience (clinic and research) in this field for more than 20 years. The purpose is to provide the clinician with an-up-to date overview of this area.
Cigarette smoking is a chronic relapsing disease. It is defined in ICD-10, the International Classification System of Diseases from the World Health Organization (WHO) [1]. One of the most important reasons for long-term smoking is dependence on nicotine in tobacco although psychological components, habituation and genetic influences also are involved 2, 3. Specific nicotine receptors have been identified in the brain, and after destruction of these receptors in nicotine-addicted rats, they will stop their nicotine intake. When nicotine binds to these receptors dopamine is released, which is believed to be associated with the acute rewarding effect of nicotine 4, 5. However, the biochemical basis for nicotine dependence seems to be far more complex and involve several other mechanisms and mediators as dealt with in detail in review papers [4].
As with other addictions such as heroin and cocaine abuse, a smoker often has to quit several times before becoming a permanent ex-smoker. The relapse after smoking cessation is highest during the first 3-6 weeks and then gradually declines [6].
A typical abstinence curve is illustrated by the results from a large smoking cessation study with varenicline (Fig. 1)[7]. With adequate support and pharmacological therapy it is possible to achieve an initial quit rate of approximately 50-60% during the first 3 months in the so-called "cessation period". From 3 months up to 12 months almost half of the subjects relapse to smoking in the so-called "relapse period", ending up with a 1-year quit rate around 25-35% 6, 7, 8.
To stop smoking requires breaking a complex habit and addiction. To achieve reasonable quit rates, it is necessary to administer support combined with pharmacological drugs [8].
Thus, tobacco smoking can be regarded as a chronic, recurrent disorder with an expected successful cessation rate with optimal treatment of 15-35% after 1 year, similar to other addictive disorders. Several failed cessation attempts may occur before permanent abstinence is achieved.
Section snippets
Evidence for smoking cessation: different support modes
Several high quality meta-analyses have been performed in this area examining different interventions for smoking cessation including the Cochrane Database, the Fiore AHCPR (US Agency for Healthcare Policy and Research) publication from US, and NICE (National Institute for Clinical Excellence) guidelines from UK plus several others 6, 7, 8, 9, 12, 13, 14. Starting with the most minimal intervention, i.e. self-help materials for smoking cessation, an unsurprisingly low 1% increase in quit rate
Evidence for smoking cessation: pharmacological therapies
The rationale for pharmacological therapies is that, when quitting smoking, the administration of the cessation drug decreases withdrawal symptoms in the first months, thus allowing the subject to cope with the behavioral and psychological aspects of smoking.
Older agents such as clonidine and nortriptyline are effective but they are regarded as second-line drugs due to their side effects [8].
Nicotine replacement therapy (NRT), varenicline and bupropionSR are regarded first-line medications 8, 12
Evidence for smoking cessation: Other therapies
Other frequently used interventions are acupuncture and hypnosis, negative effects and cue exposure (i.e. exposing smokers to smoking cues without the opportunity to smoke). However, the evidence does not support an effect from these alternative therapies. A meta-analysis comparing active versus control acupuncture found that acupuncture was no more effective than placebo 37, 38. One study has been published using laser therapy in 320 adolescents, and did not demonstrate any effect, with a 3
Cost-effectiveness
From a large prospective study of English male doctors followed for 40 years it was found that the relative risk for death was 1.8 for smokers compared to never smokers, with an annual mortality rate per 100,000 of 1.6 for coronary heart disease, 12.6 for COPD and 14.9 for lung cancer [42] (Table 3).
Updated data calculating mortality from smoking in developed countries during 1950-2000 have been published. The health problem of smoking is large; in the 25 countries that were members of the EU
Model study in smoking cessation
The Lung Health Study I (LHS) is an exemplary smoking cessation model study (Fig. 3). The LHS was a multi-centre randomized study of smoking intervention versus usual care, also testing an inhaled anti-cholinergic bronchodilator. A total of 5,887 subjects with mild COPD [i.e. a mean FEVi of 75% predicted, 2.7 L (SD 0.6 L)] were enrolled in the study. They had a mean age of 48 years with a smoking history of 40 pack-years [44]. During the first 3 months an intensive 12-session smoking cessation
Nicotine vaccination
Smokers have no antibodies to nicotine as it is a small molecule. The rationale for nicotine vaccination is that the vaccine (nicotine bound to a hapten) will induce antibodies against nicotine, and as the nicotine from tobacco is bound in the blood by these antibodies, less nicotine will reach the brain. Phase I and II studies have evaluated 3 different vaccines, NicVAX, NICQb, and TA-NIC 58, 59, 60. Dosing has been 2-6 injections with an interval of 2-4 weeks and a later booster dose. Marked
Conclusions
In 25 EU countries and in the United States, the annual excess deaths due to smoking reach 655,000 and 512,000, respectively. An annual increase in relative mortality of 1.8 is expected in smokers compared to never-smokers. Smoking cessation interventions are very cost-effective with a cost of €400–1,500 per QALY gained. NRT, varenicline and bupropionSR have scientific, well-documented efficacy in smoking cessation. Combination with counseling increases abstinence rates parallel to the
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