Medication Treatments for Nicotine Dependence PDF

Preface

Tobacco dependence constitutes a serious public health problem. It is estimated that approximately 1.1 billion people worldwide use tobacco [1]; furthermore, it is estimated that nearly 10 million people each year die from tobacco-related medical illnesses, including approximately 440,000 in the United States. Nonetheless, nicotine addiction is emerging as a treatable disorder, and we are fortunate to have several agents approved throughout the world for nicotine dependence, including the nicotine replacement therapies (NRTs) and sustained-release bupropion. Furthermore, there exist powerful behavioral and psychotherapeutic interventions, whether used alone or in combination with medications. Two factors appear to limit the usefulness of existing treatments: (1) their availability and accessibility, and (2) their tolerability and effectiveness. In clinical trials, these treatments are associated with short-term success (e.g., 2 to 3 months), but significant long-term success in achievement of smoking cessation (e.g., 6 to 12 months and longer) has not been readily achieved. In fact, although the prevalence of tobacco use through cigarette smoking appears to have decreased in the Western world in the past 40 years, a significant number of people (approximately 22% in the United States) continue to smoke and appear to be less able to quit smoking. These so-called "hard-core" smokers appear to have a history of multiple quit attempt failures and frequently the presence of comorbid psychiatric, substance use, and medical disorders [2]. Furthermore, these smokers seem to be less inclined to utilize behavioral treatments for their nicotine addiction and are more likely to use medications for smoking cessation, often without concomitant behavioral therapy [3,4]. In addition, not all smokers are able to tolerate or respond to current medication treatments. Thus, the development of new and more effective medications for treating nicotine dependence is an area of significant therapeutic importance, and one made increasingly more viable given the vast increase in our knowledge about the actions of nicotine and tobacco components on the brain using the modern tools of basic and clinical neuroscience. As this knowledge base continues to grow, and as more investigators from a broad range of fields become interested in the neurobiology of nicotine and tobacco and the implications for development of new pharmacological treatments, a book that comprehensively reviews currently available and novel medication approaches to the treatment of nicotine dependence and their neuroscientific basis seems warranted.

Accordingly, this book provides detailed overviews of the basic neuroscience relevant to medications development for nicotine, a review of current medications (both approved for this indication and available medications that have been used off-label to treat nicotine addiction), and an overview of the new medications and medication classes that are in development, along with new biological approaches (e.g., pharmacogenetics and neuroimaging) that could help to define subtypes of smokers who may respond selectively to certain agents. Toward this goal, we have assembled contributions from some of the leading basic and clinical scientists in the nicotine- and tobacco-dependence research community. Part 1 reviews the basic pharmacology and physiology of nicotine and nicotinic receptors, as well as how animal models of nicotine addiction may help to identify promising candidate therapies. Part 2 reviews the first-line, approved medications for nicotine addiction, including NRTs (e.g., gum, patch, nasal spray, inhaler, and lozenge) and sustained-release bupropion, while Part 3 discusses second-line medications, including tricyclic antidepressants, monoamine oxidase inhibitors, clonidine, and opioid antagonists. Part 4 reviews promising medications that are in development or that have considerable potential for development as nicotine-dependence treatments, including cannabinoid receptor (CB₁ ) antagonists, dopamine D 3 receptor partial agonists, the nicotine vaccine, GABAergic and glutamatergic agents, and nicotinic acetylcholine receptor subtype-specific partial agonists. In Part 5, a series of chapters addresses special topics such as the combination of medications with behavioral treatments, the use of medications in smokers with comorbid psychiatric and substance use disorders, and the application of neuroimaging and pharmacogenetic approaches to medication development for nicotine dependence. At the conclusion of the book, two perspectives are provided on medication development for nicotine dependence, the first by Ivan Montoya, M.D., and Francis Vocci, Ph.D., of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, and the second by Bernard Le Foll, M.D., Ph.D., of the University of Toronto, that address future directions for research on medication development for nicotine dependence and its implications for clinical practice.

It is our hope that this book will be a useful primer and resource for basic and clinical investigators, either established in or new to research on nicotine and tobacco; for students from a broad range of disciplines, including pharmacology, psychology, public health, and medicine; and for clinicians (physicians, nurses, psychologists, and smoking cessation counselors) who treat nicotine dependence on the front lines. Hence, we hope that readers will take home the message that we are entering a "Renaissance" period for medication treatment in the nicotine and tobacco treatment field that promises to provide us with improved pharmacological tools to tackle this most serious of worldwide public health problems.

I gratefully acknowledge the hard work and academic support in the conceptualization and editing of this book of my colleague Andrea H. Weinberger, Ph.D.; the editorial support of Ms. Erin L. Reutenauer, Taryn M. Allen, and the other staff in the Yale University Program for Research in Smokers with Mental Illness (PRISM); our research support from the National Institute on Drug Abuse; and the critical reviews of chapter manuscripts by Ivan Berlin, M.D., Ph.D.; Ronald Lukas, Ph.D.; and Daniel McGehee, Ph.D. Finally, I want to thank my wife, Sarah Graves, for her support during the many hours of after-hours editing that went into this book, and to my daughter, Emma, who makes it all worthwhile.