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Introduction

  • Stephen I. Rennard
    Correspondence
    Requests for reprints should be addressed to Stephen I. Rennard, MD, Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5885.
    Affiliations
    Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska
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      Cigarette smoking is arguably the most important preventable cause of disease in the developed world. Formerly regarded solely as a “lifestyle choice,” smoking is now recognized as a chronic, relapsing disorder.

      Fiore MC, Bailey WC, Cohen SJ, et al., for the Guideline Panel. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service. (in press).

      Many serious chronic diseases—including atherosclerotic cardiovascular disease, cancer, chronic obstructive pulmonary disease, peptic ulcer, and osteoporosis, to mention only a small fraction, are—at least in part— the secondary consequences of cigarette smoking.
      US Dept of Health and Human Services
      The Health Consequences of Smoking: A Report of the Surgeon General.
      • Rennard S.I.
      • Hepp L.
      Cigarette smoke induced disease.
      The clinician who is faced with prevention and treatment of these myriad conditions, therefore, must be able to address cigarette smoking as a primary disorder. The 4 articles in this supplement to The American Journal of Medicine provide the clinician with practical information to assess and treat tobacco use in patients, along with an update on the scientific basis for the current clinical strategies.
      Over the last several decades, considerable advances have been made in the understanding of addictive disorders in general, and of nicotine addiction specifically. In the first article, Dr. Neal L. Benowitz succinctly reviews the pathways by which nicotine leads to effects in the central nervous system. Like all addicting drugs, nicotine causes a complex set of psychological, biochemical, and cellular effects. These directly lead to the changes in mood and pleasure that smokers often find satisfying. In addition, chronic occupancy of nicotinic receptors in the brain can lead to an increase in receptor number and to the desensitization of their response to nicotine. The desensitized receptors signal through alternate pathways. In the absence of nicotine, responsiveness of the receptors is reestablished. These changes likely lead to the well-recognized withdrawal syndrome. Because the amelioration of withdrawal symptoms can be achieved with relatively low doses of nicotine, this provides a mechanistic rationale for partial nicotine replacement to facilitate smoking cessation.
      As reviewed by Dr. Benowitz, the potentiation of conditioning is an important effect of nicotine. Thus, the association of smoking with a variety of activities is more than just habit; it represents a pharmacologically reinforced conditioned response. Smoking cues, therefore, should be recognized by the clinician for what they are: strong factors that contribute to persistence of smoking. Current therapy directed against this aspect of smoking is largely nonpharmacologic. Recognizing that biochemically driven withdrawal and conditioned behavioral responses both contribute to persistence of smoking helps explain the synergistic benefits when behavioral programs and other nonpharmacologic support are combined with pharmacotherapy.
      A broad range of nonpharmacologic support strategies are available, including behavioral, cognitive, and motivational interventions. In the second article, Dr. Raymond Niaura describes these interventions, assesses their relative merits, and provides a useful table of Web sites and contact information. In general, more support is better. More specifically, support tailored to individual smokers is likely to be most effective. However, even modest generic support, such as providing brochures, is of some benefit. With the availability of telephone quit lines, online quit support, and a variety of more intensive programs, there are many effective options available for individual smokers. Understanding the appropriate use and availability of these intervention modalities is crucial for the clinician. Nonpharmacologic interventions can include public health measures in addition to individually based interventions. For example, raising the price of cigarettes through taxation or other means has been shown to decrease both smoking initiation and smoking prevalence.
      • Sweanor D.T.
      Tobacco taxes: the Canadian experience.
      Dr. Niaura also reviews other community-based programs that can have an impact on smoking behavior.
      Current recommendations suggest that the clinician should provide each smoker making a quit attempt with the best possible chance to succeed.

      Fiore MC, Bailey WC, Cohen SJ, et al., for the Guideline Panel. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service. (in press).

      Based on contemporary research, this means providing both nonpharmacologic support and pharmacotherapy.

      Fiore MC, Bailey WC, Cohen SJ, et al., for the Guideline Panel. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service. (in press).

      The currently available pharmacotherapies are reviewed in the article by Dr. Mitchell Nides, including the various forms of nicotine replacement therapy (NRT). Although they have similar efficacy, these modes of administration differ considerably, and evidence that individual responses vary with different formulations is reviewed. Dr. Nides also describes the evidence showing that patients who are allowed to sample different formulations of NRT before initiating therapy may be more adherent, and thus more successful.
      • Schneider N.G.
      • Terrace S.
      • Koury M.A.
      • et al.
      Comparison of three nicotine treatments: initial reactions and preferences with guided use.
      For these reasons, clinicians assisting smokers in their efforts to quit require familiarity with all of the various formulations.
      Dr. Nides also reviews non-nicotine medications, which can also be useful aids in helping smokers to quit. These include 2 agents approved to aid cessation (bupropion and varenicline), as well as 2 agents that are available off label (nortriptyline and clonidine). The use of these agents and their limitations, as well as several agents currently in development, is discussed. Consideration is also given to combination of pharmacotherapies to improve efficacy.
      Varenicline, the newest agent approved for smoking cessation therapy, appears to increase the odds of abstinence to a greater extent than other currently available treatments.
      • Jorenby D.E.
      • Hays J.T.
      • Rigotti N.A.
      • et al.
      Varenicline Phase 3 Study Group
      Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.
      • Gonzales D.
      • Rennard S.I.
      • Nides M.
      • et al.
      Varenicline Phase 3 Study Group
      Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.
      In the final article, Dr. J. Taylor Hays and colleagues review the rationale for the development of this drug, which is the first non-nicotine agent developed specifically for smoking cessation, and its mechanism of action. The results of 5 recent clinical trials are summarized in detail. Varenicline has become popular with clinicians because it is an oral tablet and, thus, is relatively easy to use. It has an acceptable adverse effect profile, although treated patients should be monitored by their clinician and family for mood and behavioral disturbance, is more effective than bupropion (a first-line pharmacotherapy for smoking cessation), and may help with relapse prevention. The information collected in this review, therefore, is likely to be useful to clinicians who are prescribing, or who wish to begin prescribing this agent to eligible patients.
      It is no longer adequate simply to recommend smoking cessation. The classification of smoking as a chronic disorder requires that it be addressed systematically with appropriate therapy.

      Fiore MC, Bailey WC, Cohen SJ, et al., for the Guideline Panel. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service. (in press).

      Although each is effective alone, there are clear synergies when behavioral support and pharmacotherapy are used in combination. Because there are several types of both nonpharmacologic support and pharmacotherapy, the best results occur when clinicians individualize a specific therapeutic program for each patient. In addition, recognizing that smoking is a relapsing disorder, the clinician must be prepared to readdress the problem of smoking on a regular basis and to re-treat patients who backslide. The currently available modalities offer much to the healthcare provider treating patients who smoke. The articles in this supplement provide information that is likely to be useful in this task.

      Author disclosures

      Stephen I. Rennard, MD, has served on advisory boards or as a consultant for Adams, Almirall, Altana, AstraZeneca, Bend, Biolipox, Centocor, Critical Therapeutics, Dey, GlaxoSmithKline, ICOS, Johnson and Johnson, Novartis, Ono Pharma, Parengenix, Pfizer Inc, Roche, Sankyo, sanofi-aventis, Schering-Plough, and Talecris; has received speaking fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Otsuka, and Pfizer Inc; and has also received laboratory and industry grants from Almirall, Altana, Astellas, Centocor, GlaxoSmithKline, Nabi, Novartis, and Pfizer Inc.

      References

      1. Fiore MC, Bailey WC, Cohen SJ, et al., for the Guideline Panel. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service. (in press).

        • US Dept of Health and Human Services
        The Health Consequences of Smoking: A Report of the Surgeon General.
        US Dept of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA2004
        • Rennard S.I.
        • Hepp L.
        Cigarette smoke induced disease.
        in: Stockley R. Rennard S. Rabe K. Celli B. Chronic Obstructive Pulmonary Disease. Blackwell, Malden, MA2006: 385-396
        • Sweanor D.T.
        Tobacco taxes: the Canadian experience.
        Alaska Med. 1996; 38: 40-41
        • Schneider N.G.
        • Terrace S.
        • Koury M.A.
        • et al.
        Comparison of three nicotine treatments: initial reactions and preferences with guided use.
        Psychopharmacology (Berl). 2005; 182: 545-550
        • Jorenby D.E.
        • Hays J.T.
        • Rigotti N.A.
        • et al.
        • Varenicline Phase 3 Study Group
        Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.
        JAMA. 2006; 296: 56-63
        • Gonzales D.
        • Rennard S.I.
        • Nides M.
        • et al.
        • Varenicline Phase 3 Study Group
        Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.
        JAMA. 2006; 296: 47-55