Vol. 26 No. 1 July 2003 Journal of Pain and Symptom Management 655

Special Article Definitions Related to the Medical Use of : Evolution Towards Universal Agreement Seddon R. Savage, MD, MS, David E. Joranson, MSSW, Edward C. Covington, MD, Sidney H. Schnoll, MD, PhD, Howard A. Heit, MD, and Aaron M. Gilson, PhD Department of (S.R.S.), Dartmouth , Hanover, New Hampshire; New Hampshire Regional Medical Treatment and Education Project (NH ReMOTE) (S.R.S.), Bradford, New Hampshire; Pain & Policy Studies Group (D.E.J., A.M.G.), Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin; Department of (E.C.C.), Cleveland Foundation, Cleveland, Ohio; Departments of Internal and Psychiatry (S.H.S.), Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia; Department of Health Policy (S.H.S.), Purdue Pharma L.P, Stamford, Connecticut; and Department of Medicine (H.A.H), Georgetown University School of Medicine, Washington, DC, USA

Abstract Misunderstandings regarding the nature and occurrence of have historically been barriers to the appropriate treatment of pain and have stigmatized the medical use of opioids. This article reviews the evolution of nomenclature related to addiction, presents current scientific understanding of addiction that may help shape universally acceptable terminology, and discusses an integrated effort of pain and addiction professionals to reach consensus on addiction-related terms. The article suggests key principles that may clarify terminology including: clear differentiation of the concepts of addiction and physical dependence, conceptualization of addiction as a multidimensional disease, and use of a label for the phenomenon of addiction that does not include the ambiguous term “dependence.” More universal agreement on terminology related to addiction is expected to improve the treatment of both pain and addictive disorders; improve communication between providers, regulators, and enforcement agencies; and reduce health care and other societal costs. J Pain Symptom Manage 2003;26:655–667. Ć 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Key Words Opioids, addiction, nomenclature, terminology, physical dependence, pain, abuse

Introduction Address reprint requests to: Seddon R. Savage, MD, MS, Pain is among the most common complaints 135 East Main Street, Bradford, New Hampshire for which individuals seek medical attention; 03221, USA. the evaluation and treatment of pain is there- Accepted for publication: December 12, 2002. fore integral to the practice of medicine. The

Ć 2003 U.S. Cancer Pain Relief Committee 0885-3924/03/$–see front matter Published by Elsevier Inc. All rights reserved. doi:10.1016/S0885-3924(03)00219-7 656 Savage et al. Vol. 26 No. 1 July 2003

commitment of the healthcare community to addiction. In recent years, research has con- effective management of pain has increased tributed significantly to understanding of the substantially in recent years. This is reflected in neurobiological basis of addiction. This under- a number of nationwide initiatives including standing can provide a rational foundation the new standards for pain assessment and man- for the development of universally acceptable agement required for accreditation by the Joint definitions related to addiction. Recognizing Committee on Accreditation of Healthcare the need for clarification of terminology, three 1 Organizations and the “Pain as the Fifth Vital national professional organizations interested Sign” initiative of the Veterans Administration in the interfaces between addiction and pain 2 Medical System. treatment recently collaborated to develop The important role of opioid in consensus definitions. the treatment of pain, including some types The purpose of this article is three-fold: 1) of chronic noncancer-related pain, has been to review relevant aspects of the scientific un- affirmed in recent years by numerous national derstanding of addiction and opioid pharma- professional and regulatory organizations, in- cology that are the natural foundation for cluding the American Academy of Family Physi- 3 terminology related to addiction; 2) to describe cians, the American Pain Society (APS), the the evolution of terminology currently in use American Academy of Pain Medicine (AAPM),4 related to addiction; and 3) to examine the im- the American Society of Addiction Medicine plications for clinical care and public policy of (ASAM),5 the Federation of State Medical consensus definitions developed by ASAM, APS, Boards,6,7 and the United States Enforce- and APPM. ment Administration.3 An obstacle to effective pain treatment has been misunderstanding of the nature and risk of addiction when using opioids.8,9 Scientists, clinicians, regulators, and the lay public often Scientific Basis use disparate definitions of addiction, and of Addiction-Related Terms many organizations interested in problems of addiction endorse conflicting definitions and Three fundamental concepts must inform diagnostic criteria. Such disparities may under- terminology related to addiction in order for mine appropriate clinical management of both it to reflect current scientific and clinical un- pain and addiction, thereby leading to unneces- derstanding: 1) although some produce sary pain and disability, misidentification of pleasurable reward, critical determinants of ad- addiction, and misuse of medications. diction rest also with the user; 2) addiction is a The National Co-morbidity Study suggests multidimensional disease with neurobiological that up to14% of Americans will develop alco- and psychosocial dimensions; and 3) addiction hol addiction and up to 7.5% will develop addic- is a phenomenon distinct from physical de- tion to illicit drugs over their lifetimes.10,11 pendence and tolerance. Historically, terminol- Cross-addiction to more than one substance ogy has not clearly reflected these essential is common.12 For hospitalized patients the prev- elements and, despite significant growth in un- alence of an addictive disorder is found to be derstanding of the scientific basis of addic- 19–25%.13,14 Most persons, including those with tion, definitions and diagnostic criteria based addictive disorders, require opioids for the on obsolete conceptualizations of addiction treatment of pain at some point during their persist. lifetimes in the context of , injury, acute medical illness, or chronic disease. Given the relatively high rates of both addictive disorders Reward and Addiction and pain, misunderstandings regarding addic- All drugs that are associated with the develop- tion related terminology can have a significant ment of addiction are capable of producing negative impact on . reward; that is, they are self-administered by Confusing addiction-related terminology has some animals and may produce pleasure in a long history, likely reflecting poor under- humans, especially when used in a manner re- standing of the phenomenology and biology of sulting in rapid increases in brain levels.15,16 Vol. 26 No. 1 July 2003 Definitions Related to the Medical Use of Opioids 657

Reward appears to be mediated through in- dependence” may be one aspect of the phe- crease in synaptic dopamine in the limbic nomenology of addiction, but it may also occur system, including the nucleus accumbens and in relation to therapeutic use of medications. the ventral tegmental area. Addiction is thought It is natural, for example, for persons who have to occur in vulnerable individuals when re- severe pain that is relieved by continuous use of peated rewarding drug use triggers a biologic opioids to feel anxious or concerned regarding change leading to a protracted drive to use possible loss of analgesia and hence to have a the drug,15 resulting in preoccupation with use, psychological, as well as physiological, depen- craving, compulsive use, impaired control over dence on their medications; this is not addic- use, or continued use despite harm. The nature tion, but might reasonably be referred to as of the biological changes induced by rewarding psychological dependence. In order to facilitate drugs and manifesting as addiction are not fully accurate understanding of addiction, it is im- understood, but are believed to be related to portant that the nomenclature of addiction re- dysregulation of brain reward circuits and physi- flect the full biopsychosocial dimensions of ologic stress responses.16 Genetic factors are the disease, not only the psychological dimen- thought to significantly influence vulnerability sion as reflected in terms such as “psychic” or to addiction.17 Some individuals have rela- “psychologic” dependence. tively low predisposition to developing addic- tion with drug exposure and may use drugs Physical Dependence and Tolerance repeatedly in a manner that produces reward Physical dependence and tolerance are forms without the development of addiction,18 of physiologic adaptation to the continuous whereas others rapidly develop addiction fol- presence of certain drugs in the body. Physical lowing minimal exposure to rewarding drugs. dependence occurs not only to drugs with reward potential, such as opioids and benzodi- azepines, but also to those with little or no Multidimensional Disease reward potential, such as alpha-2 adrenergic Like many other chronic conditions, such as agonists (e.g., ), and tricyclic anti- diabetes, cardiovascular disease, and asthma, . The hallmark of physical depen- addiction is a multidimensional disease.19 Al- dence is the appearance of a withdrawal though a neurobiological predisposition is syndrome when the drug effect significantly thought to be important to the evolution of diminishes or stops. Drugs from different addiction, psychological and social factors are classes produce different types of withdrawal also important, particularly as they shape pat- syndromes. The syndrome terns of risky drug use in vulnerable individuals includes autonomic signs such as diarrhea, rhi- and sustain drug use over time.20 In addition, norrhea, and piloerection, as well as central many studies suggest that stress may be a criti- neurologic arousal with sleeplessness, irrita- cal element in the development of addiction bility, and psychomotor agitation. A noradren- in some settings.21 Psychosocial factors are ergic mechanism in the locus ceruleus appears also important influences on recovery from largely responsible for the mediation of opioid addiction.22,23 withdrawal, as distinct from the dopaminergic Some terms currently used in relation to mechanism and limbic sites associated with addiction reflect only the psychological dimen- reward.24 sion of the illness, tending to obscure its Although physical dependence can occur in multidimensional nature. Although the term the presence of addiction, it is not inevitable. “psychic reward” is a reasonable description of For example, individuals who use heroin in a the subjective pleasure experienced with abuse binge pattern and have no recent use are not of certain drugs, use of the term “psychic (or likely to be physically dependent on the drug, psychological) dependence” to mean addiction but may be addicted, experiencing craving suggests that addiction is due only to cogni- when the drug is not available and relapsing into tive, affective, or other psychological processes, compulsive use when it is. On the other hand, which is not supported by current scientific physical dependence often occurs without thinking that recognizes a critical role of addiction. Many individuals who use opioids neurobiological mechanisms. “Psychological on a long-term basis for pain control develop 658 Savage et al. Vol. 26 No. 1 July 2003

physical dependence, but experience no crav- Drugs that were prone to abuse were designated ing, compulsive behavior, or other indications as causing either one or the other of these two of addiction to the drug. states, depending on their perceived effects. Similar to physical dependence, tolerance is “Addiction” was viewed primarily as a direct a physiologic adaptation to the presence of a effect of certain drugs, and secondarily due to drug in the body such that increased doses are the psychologic make-up of the drug taker: required to produce the pharmacologic effects “[ and morphine-like drugs] will initially resulting from smaller doses. Tolerance always produce compulsive craving, depen- may be present in addiction, but it can also dence, and addiction in any individual … occur in the absence of addiction, as when sooner or later there must come a time when drugs are used therapeutically over a period the use of the drug cannot be interrupted with- of time. out significant disturbance, always psychic 29 Until recently, physical dependence and tol- (psychological) and sometimes physical.” erance were thought to be important, if not “Habituation” was viewed as occurring in re- essential, elements in addiction. Much early sponse to other drugs “which never produce animal research on addiction measured with- compulsive craving, yet their pharmacologic drawal as the critical indicator of addiction. action is found desirable to some individuals However, this model was unable to explain high to the point that they readily form a habit of 29 relapse rates occurring long after completion of administration, an habituation.” The distinc- tion between the two terms lacked clarity and withdrawal or the observation that addiction is 30 uncommon in patients who become physiologi- confused most professionals. cally dependent while using opioids for pain In 1957, the WHO Expert Committee on control. Recent research on addiction mecha- Addiction-Producing Drugs introduced the terms “psychic (psychological) dependence” nisms has therefore shifted to the study of 31 limbic reward systems.25,26 Although physical and “physical dependence.” Physical depen- dependence will lead some animals to self- dence was reflected in the development of an abstinence syndrome. Psychic dependence was administer opioids to avoid the noxious ex- not defined. Addiction was characterized by the perience of withdrawal, and withdrawal may presence of both physical and psychological intensify the desire to use opioids in individuals dependence and was viewed as primarily drug- who are addicted to opioids,27 considerable induced. Habituation was characterized by psy- clinical experience indicates that most humans chological dependence and was thought to be who have been physically dependent on pre- primarily due to the psychological make-up of scribed opioids are able to withdraw from them the user. easily when pain is resolved and not return to In 1964, WHO stopped using the terms non-therapeutic use if the medications are ta- 28 “addiction” and “habituation” altogether and pered. Contemporary research on addiction introduced in their place the term “drug depen- mechanisms in both humans and animals sup- dence,” noting that dependence, either psycho- ports the view that addiction is a biologically logical or physiologic or both, was a common complex phenomenon, driven significantly feature of both conditions.32 The 1964 report by limbic reward mechanisms, that may occur further classified different types of dependence with or without the physiologic adaptations of relating to specific substances, such as “drug 16 physical dependence and tolerance. dependence of the morphine type” or “drug dependence of the type,” and de- scribed the perceived relative contributions of Historical Perspective on Terminology psychic and physical dependence in each of The Evolution of WHO Addiction-Related Terms the given types. The development of an absti- A review of the World Health Organization’s nence syndrome was considered the “most char- (WHO) efforts to develop definitions related acteristic and distinguishing feature of drug to addiction provides an interesting window on dependence of the morphine type” which also the complexities of the evolution of terminol- included “an overpowering desire or need to ogy. In 1952, in connection with its role in the continue taking the drug…, a tendency to in- international control of drugs, the WHO used crease the dose owing to tolerance…, and psy- the two terms “addiction” and “habituation.” chic dependence on the effects of the drug Vol. 26 No. 1 July 2003 Definitions Related to the Medical Use of Opioids 659

related to a subjective and individual apprecia- In 1998 the Expert Committee replaced the tion of the effects of the drug” (p. 13).32 term “drug dependence” with “dependence In 1969, the WHO Expert Committee on syndrome,” but reaffirmed its 1993 defini- Dependence Producing Drugs was renamed tion without revisions.35 The 1998 term the WHO Expert Committee on Drug Depen- “dependence syndrome” and the 1993 defini- dence. The Committee reconceptualized the tion “withdrawal syndrome” represent the cur- definition of “drug dependence” to include sig- rent WHO nomenclature. nificant behavioral criteria and to explicitly acknowledge that drug dependence is due to both host and drug factors: Current Status of Other A state, psychic and sometimes also physical, Addiction-Related Definitions resulting from the interaction between a International Diagnostic Classification living organism and a drug, characterized by Like the WHO, the International Classifica- behavioral and other responses that always tion of Diseases (ICD-10)36 currently uses the include a compulsion to take the drug on term “dependence syndrome.” ICD-10 provides a continuous or periodic basis in order to clinical guidelines for diagnosing the syn- experience its psychic effects, and sometimes drome. An individual must meet at least three of to avoid the discomfort of its absence. Toler- 33 six features to be identified with dependence ance may or may not be present (p. 6). syndrome. Of the six criteria, four relate to com- In 1993, the WHO Expert Committee on pulsivity: 1) a persistent strong desire to take a Drug Dependence noted the potential for drug, (2) difficulty controlling drug use, (3) confusion between the terms “physical depen- impairment of function, including neglect of dence” and “drug dependence” and substituted pleasuresand interests,and(4) harm to self.The the term “withdrawal syndrome” for “physical remaining two factors relate to the evidence of dependence” (pp. 5–6).34 The term “drug de- withdrawal symptoms and tolerance. pendence” was defined in the 1993 report as: Under the ICD-10 classification, as under the current WHO formulation, a person using opi- a cluster of physiological, behavioral and cog- oids prescribed for pain who demonstrates nitive phenomena of variable intensity, in opioid tolerance and physical dependence which the use of a (or would not meet criteria for addiction unless drugs) takes on a high priority. The necessary they additionally meet at least one of the four descriptive characteristics are preoccupation conditions characteristic of compulsive use. with a desire to obtain and take the drug and Compulsive use of a drug, under these two for- persistent drug-seeking behavior. Determi- mulations, remains the essential component of nants and problematic consequences of drug dependence syndrome, whereas withdrawal dependence may be biological, psychological symptoms or tolerance are by themselves insuf- or social, and usually interact (p. 5).34 ficient for an affirmative diagnosis.

Tolerance was defined for the first time, as U.S. Diagnostic Classification: DSM-IV “reduction in the sensitivity to a drug following The international classification of “depen- repeated administration, in which increased dence syndrome” of the ICD-10 converges doses are required to produce the same magni- considerably with the fourth edition of the tude of effect previously produced by a smaller American Psychiatric Association’s (APA) Diag- dose” (pp. 5–6).34 The Committee viewed with- nostic and Statistical Manual (DSM-IV) criteria drawal syndrome and tolerance “merely as con- for “” (p. 181).37 The sequences of drug exposure which, alone, are DSM-IV presents seven criteria, two of which not sufficient for a positive diagnosis of drug relate to expected physiological sequelae of dependence” (p. 4).34 This was an important opioid use (physical dependence and with- step towards ensuring that persons who develop drawal), and five of which are functional in physical dependence as a result of therapeutic nature. Three of seven criteria must be met opioid use are not viewed as pathologically in the context of “a maladaptive pattern of drug dependent. substance use, leading to clinically significant 660 Savage et al. Vol. 26 No. 1 July 2003

impairment or distress” in order to make a diag- Definitions in state statutes and regulations, nosis of substance dependence. Therefore, if however, often present more potentially delete- the criteria are applied as intended, pain pa- rious implications for patient care. Definitions tients using opioids effectively for pain control of “drug dependence” are currently found in should not be diagnosed as substance depen- 13 state policies.40 The following definition of dent unless they display maladaptive drug- a drug dependent person from Oklahoma law related behavior and meet criteria other than is typical of language in the other states: physical dependence and withdrawal. Drug-dependent person means a person who However, it has been pointed out that some is using a controlled dangerous substance of the five functional DSM-IV criteria might and who is in a state of psychic or physical be mistakenly applied to certain patients appro- dependence, or both, arising from adminis- priately using opioids for pain. For example, tration of that controlled dangerous sub- “substance often taken … over a longer period stance on a continuous basis. Drug than intended” (criteria 3) and “a great deal dependence is characterized by behavioral of time spent in activities necessary to obtain and other responses, which include a strong the substance” (criteria 5) might be applied compulsion to take the substance on a contin- to a patient due to unexpectedly protracted uous basis in order to experience its psychic pain and difficulty obtaining treatment.38 In effects, or to avoid the discomfort of its addition, some pain patients, distressed by absence.44 under-treated pain or other stressors, may be interpreted as having significant impairment This definition differs from current national or distress due to a maladaptive pattern of drug and international health organization stan- use, when, in fact, impairment and distress may dards because physical dependence alone ap- be due to under-treated pain. An inappropriate pears to be sufficient to classify an individual diagnosis of “substance dependence” should as drug dependent. Thus using this definition, a not occur in the context of pain treatment, patient using opioids on a long-term basis for however, if the criteria are carefully applied. the treatment of pain could be interpreted as “drug dependent.”40,45

Professional Education Textbooks U.S. Federal and State Policies The role of confusing terminology as barriers Whereas health-related organizations, such to has been recognized re- as the WHO and the APA, have significantly cently in two studies that analyzed such termi- revised addiction-related terminology over the nology in textbooks.46,47 These studies last half-century, U.S. federal and state statutes found that textbooks commonly used to edu- and regulations have not generally undergone cate nurses rarely defined addiction-related similar revision. For example, the Federal Con- terminology. When definitions were provided, trolled Substances Act (CSA) defines an they were often incorrect or inadequately distin- “addict” as a person who: guished addiction from physical dependence or tolerance. However, Ferrell and colleagues47 Habitually uses any narcotic drug so as to reported that most of the evaluated textbooks endanger the public morals, health, safety, acknowledged that lack of clear terminology or who is so far addicted to the use of narcotic contributed to inadequate pain management. drugs as to have lost power of self-control with reference to his addiction.39 AMA Council on Scientific Affairs Noting that “the confusing panoply of terms Although this definition uses archaic and cir- and definitions has tended to impede under- cular language, it does not appear to confuse standing and appropriate responses” (p. 555), addiction with physical dependence or toler- the American Medical Association’s Council ance, and thus has little potential for con- on Scientific Affairs Panel on and fusing patients using opioids for pain with Drug Addiction created a task force in the early persons who compulsively abuse opioids due to 1980s that attempted to reach consensus on addiction.40–43 addiction-related terminology.48 A panel of 80 Vol. 26 No. 1 July 2003 Definitions Related to the Medical Use of Opioids 661

experts from more than 20 professional organi- of opioids in pain treatment, and the preven- zations developed and rated definitions of 50 tion of abuse and addiction to prescribed opi- terms related to substance abuse, including ad- oids. Requisite to all these areas is the need for diction, addict, physical dependence, tolerance, and clear, shared definitions of addiction and re- chemical dependency. lated phenomena. Although substantial agreement was achie- In July 1999 the APS, AAPM, and ASAM ved, these consensus definitions contained a jointly formed the Liaison Committee on Pain curious blend of attributes that perpetuated, and Addiction (LCPA) to encourage collabora- rather than clarified, the confusion. For exam- tion between pain specialists and addiction spe- ple, addiction was reasonably defined in terms cialists on issues of common interest, including of functional phenomena as “a chronic disorder areas of research, education, clinical care, and characterized by the compulsive use of a sub- policy development. Two member appointees stance resulting in physical, psychological or and one administrative director from each orga- social harm to the user and continued use de- 48 nization meet biannually to discuss issues of spite that harm” (p. 556). The definition of common interest and to establish, pursue, and “addict,” however, included both compulsive revise specific goals (see Table 1). Between use and the expected physiologic effects of meetings, frequent communication and coordi- drugs: nation fosters progress on active projects. a person who is physically dependent on one or more psychoactive substances whose long- Development of the LCPA Definitions term use has produced tolerance, lost control At its initial meeting, the LCPA reviewed a over his intake and would manifest with- variety of interfacing issues in the fields of pain drawal phenomena if discontinuance were to and addiction and determined that the develop- 48 occur (p. 556). ment of consistent nomenclature was funda- mental to all of them. Misunderstandings Such confounding of terminology in the between regulators, health care providers, pa- course of a major national effort to achieve clar- tients, and the general public related to terms ity underscores the prevalence of confusion re- such as addiction, physical dependence, and garding the phenomena themselves. tolerance were identified as contributing to im- portant misperceptions regarding the medi- cal use of opioids in both pain treatment and addiction treatment, and leading to unneces- A Recent Effort to Achieve Consensus sary suffering, economic burdens to society, The Liaison Committee on Pain and Addiction stigmatization of the disease of addiction, Increasing cross-fertilization between the and inappropriate legal or regulatory actions fields of addiction medicine and pain medi- against patients and professionals. cine has occurred over the last ten years as areas The LCPA identified as its first priority the of mutual interest have commanded the atten- development of clear and unambiguous terms tion of professionals in both fields. These areas related to addiction that are consistent with include, among others, the treatment of pain in current scientific and clinical understanding individuals with addictive disorders, the need of pain, addiction, and opioid . to discriminate addiction from therapeutic use The ultimate goal of the definitions project is

Table 1 Members of Liaison Committee Committee Member Primary Specialty Organization Represented

Edward C. Covington, MD Psychiatry AAPM Howard Heit, MD ASAM John Hunt, MD Anesthesiology AAPM David Joranson, MSSW Public Policy APS Seddon Savage, MD (Chair) Anesthesiology APS Sidney H. Schnoll, MD, PhD /PhD-Pharmacology ASAM 662 Savage et al. Vol. 26 No. 1 July 2003

to promote the use of conceptually consistent “dependence;” clear separation of the con- definitions by clinicians, regulators, and the cepts of physical dependence, tolerance, and public in order to improve the care of persons addiction; conceptualization of addiction as a with pain and with addictive disorders through- chronic disease; and utility in distinguishing ad- out the world. diction from other forms of aberrant drug use. The LCPA’s consensus process is outlined in Table 2. The LCPA reviewed existing defini- tions and identified key scientific and clinical Use of the Term “Addiction.” The World Health concepts appropriate to informing ideal defini- Organization and ICD-10 currently use the term tions. Initial definitions were then drafted, dis- “dependence syndrome,” and DSM-IV uses “sub- cussed and revised by LCPA members. When stance dependence,” rather than the term “ad- the LCPA was satisfied with its draft, the defini- diction.” The Committee on Opportunities in tions were reviewed by other experts in the fields Drug Abuse Research of the Institute of Medicine of pain medicine, addiction medicine, public noted in 1996 that many professionals per- health, and drug regulation and revised with ceive the term “addiction” to be stigmatizing, this input. The definitions then went through and believe that use of “a less pejorative term internal review processes within each parent would help to promote public understanding organization, and were further revised by the of the medical nature of the condition” LCPA with this input. After negotiating the final (p. 20).50 The Committee also noted, however, revisions, the Boards of AAPM, APS, and ASAM that some professionals prefer the term “addic- approved the definitions and a consensus state- tion” to “dependence,” because it more clearly ment in February 2001. distinguishes compulsive drug use from phy- The LCPA developed a set of definitions that sical dependence resulting from prolonged discriminate common addiction-related terms medical use. and were acceptable to all members of the Com- The LCPA elects to use the term “addiction” mittee and the Boards of all three parent orga- for several reasons. The similarity of the term nizations.49 As such, they currently represent “physical dependence” to the terms “substance the standing definitions of all three organiza- dependence,” “drug dependence,” and “depen- tions, which believe that they fundamentally dence syndrome” is confusing, particularly to reflect current scientific and clinical under- individuals not regularly working with these dis- standing. The definitions of addiction, phy- tinctions, and may lead to misidentification of sical dependence, and tolerance are listed in Table 3. Table 3 Definitions Developed by the American Academy of Pain Medicine, the American Pain Society, and Discussion the American Society of Addiction Medicine Four Critical Elements of the Definitions Term Definition Four critical elements of the consensus defi- nitions deserve attention: use of the term Addiction Addiction is a primary, chronic, neurobiolo- gic disease, with genetic, psychosocial, “addiction” rather than a term that includes and environmental factors influencing its development and manifestations. It is characterized by behaviors that include Table 2 one or more of the following: impaired Consensus Process: Development control over drug use, compulsive use, of LCPA Definitions continued use despite harm, and craving. Physical Physical dependence is a state of adapta- • Existing definitions reviewed Dependence tion that is manifested by a drug class • LCPA definitions drafted specific withdrawal syndrome that can • Draft discussed and revised by LCPA be produced by abrupt cessation, rapid • LCPA definitions reviewed by outside experts dose reduction, decreasing blood level • Expert recommendation integrated of the drug, and/or administration of • Internal review by each parent organization of an antagonist. LCPA definitions Tolerance Tolerance is a state of adaptation in which • Parent organization recommendations integrated exposure to a drug induces changes that • Final definitions approved by all three boards in result in a diminution of one or more February 2001 of the drug’s effects over time. Vol. 26 No. 1 July 2003 Definitions Related to the Medical Use of Opioids 663

physical dependence as addiction and to trivial- currently physiologically dependent.”53 The ization of the occurrence of addiction. Second, policy also acknowledges the importance of the term “dependence” no longer reflects cur- “making careful diagnostic distinctions be- rent understanding of the scientific basis of ad- tween the physical dependence associated with diction, in that addiction appears to be driven chronic administration of opioids for relief of largely by reward phenomena rather than by pain and the disease of opioid addiction” and physical or psychological dependence. Finally, notes that only four of seven DSM-IV criteria although there is no question that stigma is were relevant to assessing opioid addiction in attached to the word “addiction,” clear under- the context of pain treatment.54 standing and appropriate use of terms will likely do more to dispel stigma and improve treat- Recognition of Addiction as a Chronic Disease. The ment than use of an arguably more benign acknowledgment of addiction as a chronic med- term such as “dependence” which introduces ical illness within the definition of addiction ambiguity. underscores the important role of in addressing the disease on a longitudinal Clear Conceptual Separation of Physical Dependence, basis. Because addiction is a serious, sometimes Tolerance, and Addiction. Past definitions of ad- life-threatening, disease, patients require inten- diction and dependence often have included sification of management when it emerges in the references to tolerance and physical depen- context of medical care, despite an occasional dence as necessary elements of addiction. impulse to discharge patients, particularly when Because scientific understanding now views addiction has resulted in the abuse of pre- these as distinct, if sometimes interrelated, phe- scribed medications. With appropriate care, nomena, it is important that this distinction treatment compliance rates and patterns of be reflected in language. of the remission and exacerbation are similar to those perception that physical dependence and toler- of other chronic illnesses.19 ance are necessarily part of addiction may lead to over-diagnosis of addiction with the thera- Other Forms of Aberrant Drug Use. The defining peutic use of opioids and other drugs and the characteristics incorporated into the definition under-recognition of addiction to substances of addiction can help distinguish it from other that do not result in demonstrable physical forms of aberrant drug use.8,61–66 Some persons dependence. have been described as “chemical copers,” and Recent changes in federal policy governing tend to use available medications, including the use of opioids in addiction treatment under- opioids, to cope with a variety of life issues for score the importance of distinguishing between which they were not intended. Such uses can addiction and physical dependence. In the past, include managing stress, relieving anxiety or the admission criteria to federally registered depression, or facilitating sleep; this also has narcotic treatment programs (NTPs) defined been referred to as self-. Usually, it “narcotic dependence,” exclusively by the pres- is helpful to identify such use, to further assess ence of physical dependence,51 making pa- the problem, and to institute more specific tients receiving opioids for pain treatment treatments. eligible for admission. Some individuals seeking Other persons divert opioids from their in- pain relief, in fact, have been admitted to NTPs tended use for a variety of reasons. Some indi- solely for the purpose of pain management, viduals obtain and use opioids to get high, but not for treatment of opioid addiction.52 This do not use the drugs in the compulsive manner practice has raised questions about appropriate that suggests addiction. Others may divert part use of limited drug abuse treatment resources or all of their prescribed opioid medications to and about barriers to pain treatment in the sell for profit. Still others may use part of their general health care system. medication for analgesia, sharing excess medi- Effective May 2001, federal policy changed cations with friends or family who also have admission criteria to opioid treatment pro- pain. When practitioners suspect aberrant drug grams to “evidence of physiologic dependence use, careful evaluation that defines the patterns and opioid addiction” with exceptions permit- and purposes of use is important to determine ting admission of some persons “who are not an appropriate clinical response. 664 Savage et al. Vol. 26 No. 1 July 2003

Clinical Importance of the Definitions treatment approaches is not likely to be ad- Healthcare professionals often underutilize dicted to the medications. opioids in pain treatment due to unrealistic At times patients with unrelieved pain may concerns about addiction.55 Although the use demonstrate a pattern of behaviors that sug- of opioid can lead to addiction in gests addiction, but that actually indicates the vulnerable individuals, these medications do need for improved pain control. The term not usually result in addiction when adminis- “pseudoaddiction” has been used to refer to tered for pain in persons with no prior history the misidentification of addiction in patients of substance abuse or addictive disorder.56,57 who exhibit such behaviors due to unrelieved However, indiscriminant prescribing of opi- pain.60 Even behaviors such as illicit drug use oids, as well as failure to monitor for the develop- and deception can and do occur in some pa- ment of abuse and addiction during treatment, tients’ efforts to obtain pain relief. Pseudo- can contribute to serious morbidity and even addiction can often be distinguished from true patient mortality.58,59 addiction by observing whether drug-seeking Although they are not intended to serve as behaviors cease when effective analgesia is formal diagnostic criteria, the LCPA defini- achieved using opioid or nonopioid treat- tions provide a conceptual framework that may ments. However, when opioids are used for an- be helpful in identifying addiction in the course algesia in some patients with addiction, they of medical treatment and in discriminating ad- may incidentally block opioid craving and help diction from therapeutic use of medications. A normalize behavior. Good clinical judgment persistent pattern of behaviors that includes must therefore be used to determine whether one or more of the defining features of addic- the pattern of behaviors signals the presence of tion (impaired control over drug use; compul- addiction or reflects the need for more effective sive use; craving; and physical, psychological, or pain treatment. social harm due to use) suggests the need for more formal assessment of the possibility that addiction is present. Public Policy Importance of the Definitions Compulsive use, craving, and impaired con- Untreated pain results not only in unnec- trol may be reflected in a patient’s inability to essary individual suffering, but in increased comply with an effective agreed-upon dosing utilization of health care resources, reduced schedule, frequent reports of lost or stolen pre- productivity, and over-utilization of disability scriptions, doctor shopping for prescriptions, support systems.67 Definitions and diagnostic abuse of non-prescribed drugs or , non- criteria that clearly discriminate between ad- compliance with non-opioid pain management diction, physical dependence, and tolerance strategies, and running out of medications encourage the development of public policies before schedule in the absence of increased that support effective pain treatment. pain. Physical, psychological, or social harm or Untreated addictive disorders may result in adverse consequences due to use may be re- significant economic costs to society, negative flected in increasing functional impairment, public health consequences, and increased persistent intoxication or sedation, negative crime.68,69 Regulatory definitions that acknowl- mood changes such as irritability, apathy or edge addiction as a chronic illness and clearly depression, increasing social isolation, and ad- distinguish it from physical dependence and verse legal or economic consequences. tolerance are critical to the development of reg- Although any of these behaviors can occur ulatory, enforcement, and healthcare policies from time to time in a non-addicted patient that effectively address addictive disorders. Cur- who is using medications therapeutically, a per- rent definitions that equate physical depen- sistent pattern requires further assessment. A dence with addiction or identify addiction as a patient who is prescribed opioids that control moral failing may lead to inappropriate use of his or her pain, is able to use them according public health and criminal justice systems, to an agreed upon schedule, does not routinely ineffective management of the disease of ad- request early refills, has stable or improving diction, persistence of stigma associated with function, reports reasonably stable pain con- addictive disorders, and misallocation of public trol, and who is willing to consider additional resources. Vol. 26 No. 1 July 2003 Definitions Related to the Medical Use of Opioids 665

Limitations of the LCPA Process understanding of these phenomena through a It may be argued that the LCPA left a number consensus process that incorporated input from of important and relevant terms undefined. a multidisciplinary group of experts. The LCPA elected to define critical terms for Efforts are currently underway to seek en- which clear consensus, based on current scien- dorsement of the key principles of the defi- tific and clinical understanding, could be nitions by professional groups representing achieved. Terms such as “abuse” and “psycho- medicine, nursing, and , as well as logical dependence” also demand clarification. from organizations representing legal, regula- However, these terms appear to be imbued with tory, and law enforcement interests. National more complex social, political, and personal organizations and agencies are encouraged to meanings, and the task of defining them in a consider the critical elements of the LCPA defi- universally acceptable manner will more likely nitions in revising their own definitions and be successful once there is more universal diagnostic criteria. agreement on the concepts of addiction, physi- cal dependence and tolerance. A second limitation is the small number of organizations involved in the consensus pro- Acknowledgments cess. However, the organizations involved are The authors wish to thank James Callahan, interdisciplinary in nature and the review pro- former Executive Director, American Society of cess included individuals from a broad range Addiction Medicine; Jeffrey Engel, Executive of disciplines and medical specialties, both from Director, American Academy of Pain Medi- within and from outside of the participating cine; and Catherine Underwood, Executive organizations. Finally, the process of devel- Director, American Pain Society, for their oping consensus inevitably requires compro- wise counsel, strong support, and organiza- mise. Different organizations and individuals tional expertise in facilitating the work of the had preferred wordings that were altered to Liaison Committee on Pain and Addiction make the definitions acceptable to all. The com- (LCPA) and the evolution of this report. The promises were made in a manner that all par- work of the LCPA has been supported by un- ticipants agreed preserved the key elements of restricted educational grants from Pfizer Phar- the definitions. maceutical, Searle, and Purdue Pharma, L.P.

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