·1 ICRO MAREMMANI THE PRINCIPLES AND PRACTICE OF METHADONE TREATMENT In memory of Vincent P. Dole, friend and magister ·1 ICRO MAREMMANI, MD Professor of Addiction Medicine University of Pisa and Siena, Italy Chief of “Vincent P. Dole” Dual Diagnosis Unit “Santa Chiara” University Hospital, Department of Psychiatry University of Pisa Co-Director of “G. De Lisio” Institute of Behavioural Sciences Pisa, Italy, EU THE PRINCIPLES AND PRACTICE OF METHADONE TREATMENT Pacini Editore Medicina, Via A. Gherardesca, 56121 Ospedaletto, Pisa, Italy, EU AU-CNS, Via XX Settembre, 83 - 55045 Pietrasanta, Lucca, Italy, EU 2· ·3 2· ·3 Contributors Emanuele Bignamini, MD Psychiatrist and Psychoanalist, Director of Department of Addiction Medicine, National Health System Local Unit, Torino, Italy, EU Stefania Canoniero, MD Psychiatrist, Addiction treatment Centre (SerT), National Health System Local Unit, Albenga and Finale Ligure, Italy, EU Barbara Capovani, MD Psychiatrist, Addiction treatment Centre (SerT), National Health System Local Unit, Pisa, Italy, EU Loretta Finnegan, MD Professor of Pediatrics, Psychiatry and Human Behavior, Thomas Jefferson University (Retired), Philadelphia, Pennsylvania USA Andrea Flego, MD Psychiatrist, Director of Department of Addiction Medicine, National Health System Local Unit (Retired) Pordenone, Italy, EU 4· ·5 Gilberto Gerra, MD Chief Health and Human Development Section, Division for Operations, United Nations Office on Drugs and Crime, Vienna Giuseppe Giuntoli, MD Psychiatrist, Medical Director of “Incontro” Therapeutic Community, Pistoia, Italy, EU Francesco Lamanna, MD Psychiatrist, Addiction treatment Centre (SerT), National Health System Local Unit, Pisa, Italy, EU Mercedes Lovrecic, MD Psychiatrist, Ministry of Health of the Republic of Slovenia and Institute of Public Heath of the Republic of Slovenia, Lubiana, Slovenia, EU Sonia Lubrano, MD Psychiatrist, Addiction treatment Centre (SerT), National Health System Local Unit, La Spezia, Italy, EU Alexander Kantchelov, MD Psychiatrist, Director of Kantchelov Clinic, Sofia, Bulgaria, EU Angelo Giovanni Icro Maremmani, MD Consultant Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), Pietrasanta, Lucca, Italy, EU Andrea Michelazzi, MD General Practitioner National Health System, Trieste, Italy, EU Matteo Pacini, MD Research Psychiatrist, “G. De Lisio” Institute of Behavioural Sciences, Pisa, Italy, EU 4· ·5 Pier Paolo Pani, MD Psychiatrist, Social-Health Service, National Health System Local Unit, Cagliari, Italy, EU Giulio Perugi, MD Professor of Psychiatry, University of Pisa, Italy, EU Director of “G. De Lisio” Institute of Behavioural Sciences Pisa, Italy, EU Dina Popovic, MD Psychiatrist, “G. De Lisio” Institute of Behavioural Sciences Pisa, Italy, EU Annella-Maria Sciacchitano, MD Pharmacologist, Addiction treatment Centre (SerT), National Health System Local Unit, Rovigo, Italy, EU Lorenzo Somaini, MD Clinical Pharmacologist Addiction Treatment Centre (SerT), National Health System Local Unit, Biella, Italy, EU Emanuela Trogu, MD Psychiatrist, Addiction treatment Centre (SerT), National Health System Local Unit, Cagliari, Italy, EU Franco Vecchiet, MD General Practitioner National Health System, Trieste, Italy, EU Andrea Vendramin, MD Professor of Pharmacology, University of Padua, Italy, EU Director of Department of Addiction Medicine, National Health System Local Unit, Padua, Italy, EU Sara Zazza, PhD Psychologist, Department of Addiction Medicine, National Health System Local Unit, Torino, Italy, EU 6· ·7 Preface Several articles in magazines and symposium speeches try to answer the ques- tion “What should the physician know?” I often feel doubts about what students should be expected to know to pass a general pharmacology examination. I usu- ally tell students they should think of themselves as athletes, while their professor should be someone with such a deep knowledge of a discipline that he or she can communicate it spontaneously. General practitioners remain athletes, with their direct experience and constant updating enhancing their skills in the handling of complex clinical syndromes and their depth of knowledge in managing specific diseases and therapeutic approaches. This explains why I feel at a loss when they ask me what the basis of pharmacological and medical knowledge should be, or what it is essential to know about specific therapeutic issues. When speaking to audiences of general practitioners, I am usually requested - when it’s a matter of explaining what disorder a drug should be used against, what the proofs and the terms of its effectiveness are, what its toxic effects are - to skip all the details and foregrounds about the pharmacological basis of how and why it works, because general practitioners are supposed not to bother much about such things. The adoption of an evidence-based substance vs. substance approach has shifted the focus of medical knowledge on to the statistical weight of clinical reports, where- as mere consistency with pathophysiological dynamics is not considered reliable as a predictor of effectiveness: in fact, clinical trials have often failed to confirm a hypothesis of effectiveness founded solely on pathophysiological speculations and open-label clinical reports. Nevertheless, the theoretical basis for the effective- ness of pharmacological treatment has not become irrelevant, and may provide warnings against risks that will not emerge from controlled clinical trials: that happened with -coxib drugs and cerivastatine, which were quickly withdrawn from the market due to surveillance warnings about toxicity - warnings which had been anticipated by preclinical pathophysiological investigations, but had not been expected on the basis of the results of later clinical trials. Often, it takes pathophysiology to inspire a clinical study, which then gives positive spin-off in return by providing evidence that deepens and enriches the level of knowledge about the biological basis of therapeutics. Medical discipline results from a con- tinuous exchange between biological research and clinical practice through the channel of statistically weighted data. 6· ·7 Returning now to the question of “What should a physician know?”, the an- swer should be translated into what each physician thinks he/she should know, into their curiosity and professional liveliness, into their need to deepen their knowledge. Both biologists and clinicians should avoid going into the fine detail of technical aspects of their practice, unless questioned about it by an audience. In any article, such details can be reported in a special section printed as a box kept separate from the main text, or else, in case of an oral presentation, the speaker may provide a reference list so that anyone can consult original data. Instead of boring an audience with superfluous notions; it is a speaker’s interest and should be within his/her grasp to know many other things that will only emerge in the open discussion of scientific issues. Actually, “What should physicians know?” should be viewed as an open-ended issue. This book is written by clinicians and appeals to clinicians. It features a great many pharmacological details about the pharmacological kinetics and dynamics of anticraving treatment. The clinical issues are discussed by psychiatrists with accuracy and by dedicating special attention to specific problems that emerge during the course of treatment, ranging between ordinary ones and quite unex- pected ones. For each situation authors discuss the possible causes and review the different therapeutic strategies. The same issues seem to recur in different chap- ters, with special regard to anticraving treatment and different ways to reach the same solution from different viewpoints, while taking into account the variability of drug-related clinical situations and the need to use a variety of starting points. For instance, treating a pregnant narcotic addict requires specific skills, while planning a treatment programme for jailed addicts calls for a specific knowledge of the prison environment and related legal issues. Nowadays, since addiction has become an endemic condition, it is expected to affect categories of individuals with higher exposure to risk factors, which probably include several psychopatho- logical syndromes. As a result, it is crucial to anticipate possible dual diagnosis patterns, so as to be able to recognize them and handle such complex situations through specific treatment approaches. Several chapters deal with psychosocial issues related to the world of addiction, with special reference to narcotics, both from a patient’s and from the physician’s point of view. This subject is faced without resorting to a meaningless even if politically correct approach. Drug addiction is presented as a psychiatric disorder and a curable condition: treatment can provide complete control of its symptoms by administering specific drugs in maintenance regimens of proved effectiveness. Other interventions may be useful, in some cases crucial, as in any other chronic disease, and comprise psychiatric and somatic treatments, individual counselling to help patients cope with the family and work environment. Authors specify the tasks of different staff members, whether medical or non-medical, who need to know how to deal with the patient, while avoiding uncertainty about profes- sional roles and hierarchical relationships. The present manual looms as an easy- to-read volume, written by skilled professionals with technical competence and an aversion for dogmatism. Prof. Alessandro Tagliamonte Professor of Pharmacology University of Sienna Italy, EU 8· ·9 Contents INTRODUCTION Definitions 11 1.1 I. Maremmani Addiction Treatment: When will Medical Principles Matter ? 17 1.2 M. Pacini and I. Maremmani Heroin Dependence 21 1.3 I. Maremmani and D. Popovic Heroin Dependence: Theory of Different Levels of Intervention 31 1.4 I. Maremmani Scientifically Based Ethical Principles in Dealing with Heroin Addicts 39 1.5 M. Pacini and I. Maremmani Pharmacology and Neurochemistry of Methadone 43 1.6 A. Vendramin and A. M. Sciacchitano Pharmacokinetics of Methadone 63 1.7 P.P. Pani Neuroendocrinologic Effects of Methadone Treatment 69 1.8 G. Gerra METHADONE TREATMENT The History of Methadone Treatment 75 2.1 M. Pacini, A.G.I. Maremmani and I. Maremmani
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