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Joranson, DE. Current Thoughts on Opioid Analgesics and Addiction. Symptom Control in Cancer Patients (Japan) 1995. 6(1):105-110.

Current Thoughts on Opioid Analgesics and Addiction

David E. Joranson

Associate Director for Policy Studies
Pain Research Group
University of Wisconsin Medical School
World Health Organization Collaborating Center

Introduction

Cancer pain is a serious public health problem and is prevalent throughout the world. Unrelieved pain destroys a person's quality of life 1) and is one of the driving forces behind interest in physician-assisted suicide and euthanasia 2) 3).

The World Health Organization has shown that pain due to cancer can be relieved using a relatively simple treatment method that involves the use of oral analgesics 4). Opioid analgesics such as codeine, fentanyl, hydromorphone, oxycodone and morphine are the cornerstones of this method.

Unfortunately, less than optimal prescribing and inadequate availability of opioid analgesics continues to be a problem in most parts of the world. This is due to a combination of factors which include the low priority of pain management, lack of education, overly restrictive drug control laws, and fear of addiction 2)5).

The fear of addiction when opioids are used to manage pain, even cancer pain, is prevalent among the public, patients health care professionals and policy-makers throughout the world 6)-11). However, this fear is not warranted and is one of the factors that can result in ineffective clinical use of opioids and reluctance on the part of policy makers to allow greater import, production and prescription of opioid analgesics 2)5).

The global consumption of morphine for medical use finally began to increase following the introduction of the WHO cancer pain relief methods 5). However, most of these increases are limited to developed countries where it is generally acknowledged that opioids are underused for the treatment of cancer pain. In Japan, the use of morphine has increased significantly, but is considerably less than in major developed countries 6). The use of pethidine, which is not recommended for chronic pain due to its toxic metabolites12), has decreased in Japan as morphine use has increased.

This paper will discuss the relation of "addiction" to the use of opioids for cancer pain and encourage health care professionals and policy markers to overcome this barrier to adequate management of pain in patients with cancer.

Why is there fear of addiction when opioids are used to manage pain?

The fear of addiction to opioid analgesics appears to be based on the widespread misperception that physical dependence is the same as addiction. Thus, the use of opioids to treat pain even cancer pain may lead to addiction. The fear of addiction comes from years of misinformation about opioids14)15), and has been reinforced in some countries by national antidrug campaigns that ignore the medical benefits of opioids13)16).

We have been so effective in warning the medical establishment and the public in general about the inappropriate use of opiates that we have endowed these drugs with a mysterious power to enslave that is overrated17).

In the past, official WHO definitions of drug abuse terms have equated addiction and drug dependence with physical dependence. Furthermore, despite the fact that physical dependence is common in the treatment of cancer pain, the definitions have failed to consider that physical dependence can occur independently within a therapeutic setting 14)-16)18)19).

The confusing nature of drug abuse terms, the low incidence of addiction among patients with cancer pain, and the inaccurate use of terms in both professional education and narcotic control laws has become an area of research and discussion 2)4)5)8)11)13)16)18)20)-24).

Definition of drug abuse terms

Historically, the WHO and its Expert Committee on Drug Dependence have produced and publicized a classification scheme of drug abuse terms that has had a great impact on medicine and drug control throughout the world. However, little attention has been given to clarifying how such terms as "addiction", "habituation" and "drug dependence" relate to the therapeutic uses and users of controlled substances.

Clearly, the WHO term "drug dependence" and its predecessors "addiction" and "habituation" are intended to refer to undesirable drug-related states that are harmful to the individual and society. However, the definition and use of these terms often do not take into account the drug-related states that benefit the individual and society. The central definitional issue appears to be that physical dependence and tolerance are often perceived as synonymous with addiction or drug dependence, even though they occur within a therapeutic setting.

WHO's initial efforts to define drug abuse phenomena emphasized the power of morphine-like drugs to produce addiction in everyone:

There are some drugs, notably morphine and pharmacologically morphine-like substances, whose specific pharmacological action, under individual conditions of time and dose, will always produce compulsive craving, dependence, and addiction in any individual ... With these drugs pharmacological action is paramount, psychological make-up adjuvant. Such drugs cause individual and sociological damage and must be rigidly controlled25).

In addition, WHO strongly suggested that medical patients who are treated with opioids will become addicted:

The cycle of administration leading to addiction may begin in legitimate medical use but becomes established as a serious problem through self-administration beyond medical need 25).

There have been attempts to clarify definitions of drug abuse phenomena14)15)26)27). In 1969, the WHO Expert Committee on Drug Dependence produced a revised definition of "drug dependence" which is in effect today. In this definition, the compulsive use of a drug for its psychic effects is the only characteristic that is both necessary and sufficient to define drug dependence. Physical dependence and tolerance may be present, but are neither necessary nor sufficient by themselves to define drug dependence.

A state, psychic and sometimes also physical, resulting from the interaction between a living organism and a drug, characterized by behavioral and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence. Tolerance may or may not be present28).

This definition made psychic dependence the only necessary condition for drug dependence and deleted physical dependence as necessary or sufficient. This was a critically important change in WHO drug abuse nomenclature which received very little attention and is not well known.

Although the WHO did not state any intent to exclude physically dependent pain patients from the new definition of drug dependence, there is evidence that WHO recognized this issue:

...there are some situations in which physical dependence may occur in the absence of significant psychic dependence29).

What is the risk of addiction/psychological dependence in cancer pain management?

The WHO Expert Committee on Cancer Pain Relief and Active Supportive Care recently reviewed the available data which "suggest that the medical use of opioids is rarely associated with the development of psychological dependence"2). Reported clinical experience supports the observation that opioid addiction (psychological dependence) is rare among pain patients, including cancer patients 30)-36).

Pseudoaddiction

The fear of addiction can be so strong that legitimate patient requests for opioid analgesics are mistaken for addictive behavior. A new term, "pseudoaddiction", has been suggested to describe an iatrogenic syndrome that appears as a result of poorly treated pain:

Inadequate treatment of the [cancer] patient's pain led to behavioral changes similar to those seen with idiopathic opioid psychologic dependence (addiction). The term pseudoaddiction is introduced to describe the iatrogenic syndrome of abnormal behavior developing as a direct consequence of inadequate pain management...Treatment strategies include establishing trust between the patient and the health care team and providing appropriate and timely analgesics to control the patient's level of pains 37).

Terminology used to train health care professionals

Drug abuse terms are often defined in the textbooks that are used to train health care professionals. If these terms are defined improperly, this can have a major negative impact on the attitudes and knowledge of professionals toward the use of opioids to treat pain.

Available information suggests that some health care professionals may have, to varying degrees. a reluctance to use opiates in the treatment of their patients. There seems to be fear among health professionals (which is shared by certain patients and their families) that the use of opiates will result in iatrogenic addiction... It has been suggested that the training or education received by many health professionals does not focus sufficient attention on the treatment of pain, on the proper use of opiates, or on the treatment of chronic or acute conditions for which those drugs are required or indicated 5).

A recent study examined the accuracy of terminology in U. S. nursing textbooks since 1985. The criterion that was used to evaluate the accuracy of the definitions was the American Pain Society definitions in "Guidelines for Analgesic Use"38) which is analogous to the WHO definition in which neither tolerance or physical dependence by themselves are sufficient to define drug dependence, or addiction.

Only one textbook correctly stated the definition of opioid addiction and its likelihood following use of opioid analgesics for pain control. Almost all of the texts used confusing terminology, and some erroneously promoted the fear of addiction when opioids are used for pain relief 24).

Terminology in laws and regulations

National governments have adopted laws and regulations controlling the uses and users of dependence-producing drugs and many of these use and define drug abuse terms. Although a comprehensive international study has not yet been accomplished, there are some examples of laws and regulations that define "addict" so as to allow pain patients who are physically dependent on opioids to be confused with addicts13). For example, New York State's definition of "addict" could include a person who is physically dependent on an opioid.

a person who habitually uses a narcotic drug and who by reason of such use is dependent thereon39).

Another provision requires that such persons be reported by their physician as addicts to the state health department40). In 1987, an oncologist was investigated and finally admonished for failing to report several "addicts" that were receiving opioids for an extended period and who were actually oncology patients13).

Nevada defines "narcotic addict" in the following way:

Narcotic addict means a person of any age who has developed a compulsion to continue taking or who has developed a psychic or physical dependence on the effects of a narcotic drug41).

The State of Colorado defines the term addict in the following way: "Addict" means a person who has a

physical or psychological dependence on a controlled substance, which dependence develops following the use of the controlled substance on a periodic or continuing basis and is demonstrated by appropriate observation and tests by a person licensed to practice medicine... 42).

The drug control law of the Republic of Colombia defines "substance dependent" as:

"dependence upon substances which have been medically qualified as toxic" 43).

The above definitions do not attempt to distinguish between addicts and the important therapeutic use of opioids as does, for example, a United States regulation which states that physicians may "administer or dispense (including prescribe) narcotic drugs to persons with intractable pain in which no relief or cure is possible or none has been found after reasonable efforts" 44).

Recognizing the confusion between addiction and physical dependence on pain management, the Medical Board of California made the following statement in its new policy on "Prescribing Controlled Substances for Pain":

...addiction should be placed into proper perspective. Physical dependence and tolerance are normal physiologic consequences of extended opioid therapy and are not the same as addiction. Addiction is a behavioral syndrome characterized by psychological dependence and aberrant drug-related behaviors. Addicts compulsively use drugs for non-medical purposes despite harmful effects; a person who is addicted may also be physically dependent or tolerant. Patients with chronic pain should not be considered addicts or habitués merely because they are being treated with opioids 45).

Conclusions and recommendations

Failure to distinguish between addiction and physical dependence increases the risk that cancer patients will not receive adequate pain relief and will therefore suffer unnecessarily. It is common for people who are trapped between their concern about addiction and their desire to relieve pain to say "So what if they are addicted, they are going to die anyway". This putatively humanitarian approach is entirely inappropriate because it perpetuates a faulty definition of addiction, it unjustly labels the pain patient as an addict, and in any case will probably not result in adequate pain relief because uncorrected knowledge about addiction and opioids will likely impede the kind of aggressive opioid therapy that some patients need.

Recently, the World Health Organization Programme on Substance Abuse was asked by the Pain Research Group at the University of Wisconsin Medical School to clarify whether a physically dependent pain patient was considered to be drug dependent (or addicted). In response, the WHO Expert Committee on Drug Dependence stated that indeed a cancer patient who is physically dependent (as indicated by a withdrawal syndrome) is not considered drug dependent:

the manifestation of withdrawal syndromes in cancer patients given opioid analgesics is not by itself sufficient evidence of dependence 46) .

Furthermore, the Expert Committee made a proactive statement on the need to improve the medical use and availability of opioid analgesics:

The Committee recommended WHO should promote the appropriate use of opioids for the relief of pain through the education of health care professionals (nurses, pharmacists, physicians), health authorities and the general public to ensure that patients with legitimate medical needs receive adequate treatment...progress has been made in increasing the appropriate use of such medications in certain countries. However, there are still many areas of the world where patients continue to suffer needless pain because of the reluctance of health care workers to provide adequate amounts of opioid analgesics46).

One of the significant barriers to cancer pain relief that must be overcome is the fear of addiction to opioids. It is unjust to confuse a patient who may benefit from the medical use of opioids with a drug abuser. Concerted efforts should be made to assure that the terminology used to describe drug abuse phenomenon in common usage, textbooks and narcotic control laws do not inappropriately affect the medical treatment of pain.

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