Defining Abuse and Addiction in the Physically Ill
Physical Dependence
Tolerance
Deficiencies in the Current Nomenclature

Substance abuse appears to be very uncommon among cancer patients. The reported prevalence of substance abuse issues in cancer patients is much lower than the prevalence in society at large, general medical populations, and emergency medical departments.[1-5] This relatively low prevalence was also reported in a Psychiatric Collaborative Oncology Group study, which assessed psychiatric diagnoses in ambulatory cancer patients from several tertiary care hospitals.[5] On the basis of structured clinical interviews, fewer than 5% of 215 cancer patients met the Diagnostic and Statistical Manual for Mental Disorders, 3rd Edition (DSM-III) criteria for a substance use disorder.[6]

The relatively low prevalence of substance abuse among cancer patients treated in tertiary care hospitals may reflect institutional biases or a tendency for patient underreporting in these settings. Drug abusers who are poor or feel alienated from the health care system may not seek care in tertiary centers. Those who are treated in these centers may not acknowledge a history of drug abuse. The low prevalence of drug abuse in cancer centers, therefore, may not represent the true prevalence among the cancer population overall. A survey of patients who were admitted to a palliative care unit found indications of alcohol abuse in more than 25% of these patients;[7] this, however, represents highly selected palliative care patients referred to a specialized inpatient unit.

Epidemiologic studies and clinical management depend on an accepted, valid nomenclature for substance abuse and addiction. The pharmacologic phenomena of tolerance and physical dependence are commonly confused with abuse and addiction. Terminology is also strongly influenced by sociocultural considerations that may lead to the sending of mixed messages in the clinical setting. The definitions of addiction and abuse that are applied to patients who are physically ill have been developed from populations of addicts who do not have physical illnesses. The clarification of this terminology is an essential step in improving the diagnosis and management of substance abuse in the palliative care setting. The list below gives the proposed definitions for these terms.

Proposed Terminology for Substance Abuse

• Physical dependence: Pharmacologic property of some drugs defined solely by the occurrence of abstinence syndrome following abrupt dose reduction, discontinuation of dosing, or administration of a pharmacologic antagonist.



• Tolerance: Diminishing of one or more of the drug effects (either favorable or adverse) that are caused by exposure to the drug; may be pharmacologic or the result of associative learning.



• Substance abuse: Use of a substance in a manner outside sociocultural conventions; according to this definition, all use of illicit drugs and all use of licit drugs in a manner not dictated by convention (e.g., according to physician’s orders) is abuse.



• Addiction: Commonly used term that does not appear in current psychiatric nosologies but can be taken to mean the aberrant use of a substance in a manner characterized by loss of control, compulsive or escalating use, preoccupation, and continued use despite harm.

Physical dependence is defined solely by the occurrence of a characteristic withdrawal or abstinence syndrome following discontinuation of dosing, abrupt dose reduction, or administration of a pharmacologic antagonist.[8-10] Neither the dose nor duration of administration of opioids required to produce clinically significant physical dependence in humans is known. Most practitioners assume that the potential for abstinence syndrome exists after opioids have been administered repeatedly for only a few days.

Physical dependence is not apparent unless abstinence is induced. In the clinical setting, physical dependence on an opioid is not considered a problem as long as patients are told to avoid abrupt discontinuation of therapy and to avoid the inadvertent administration of an opioid antagonist (including an analgesic from the agonist-antagonist class).

There is often confusion among clinicians about the differences between physical dependence and addiction. Physical dependence, like tolerance, has been suggested to be a component of addiction,[11,12] and the avoidance of withdrawal has been postulated to create behavioral contingencies that reinforce drug-seeking behavior.[13] These speculations, however, are not supported by experience with opioid therapy for chronic pain. Physical dependence does not preclude the uncomplicated discontinuation of opioids during multidisciplinary pain management of nonmalignant pain.[14] Opioid therapy is routinely stopped without difficulty in cancer patients whose pain disappears following effective antineoplastic therapy. Indirect evidence for a fundamental distinction between physical dependence and addiction is provided by animal models of opioid self-administration, which have demonstrated that persistent drug-taking behavior can be maintained in the absence of physical dependence.[15]

Tolerance, a pharmacologic property defined by the need for increasing doses to maintain effects,[8,9] has been a particular concern with opioid therapy. Clinicians and patients commonly express concern that tolerance to the analgesic effects of opioids may compromise the benefits of therapy and lead to a requirement for progressively higher and ultimately unsustainable doses. It has been speculated that the development of tolerance to the reinforcing effects of opioids and the consequent need to increase doses to regain these effects is an important element in the pathogenesis of addiction.[13]

Despite these concerns, extensive clinical experience with opioid drugs given for medical reasons has not confirmed that tolerance causes substantial problems.[16,17] Numerous surveys have demonstrated that most patients can attain stable opioid doses with a favorable balance between analgesia and side effects for prolonged periods.

Clinical observation does not support the conclusion that analgesic tolerance is a substantial contributor to the development of addiction. It is widely accepted that addicts who do not have a medical disorder may not have any of the manifestations of analgesic tolerance. Opioid-treated patients who present with analgesic tolerance typically do so without evidence of abuse or addiction.

The definitions of tolerance and physical dependence highlight deficiencies in the current nomenclature applied to substance abuse. The terms addiction and addict are particularly troublesome. In common parlance, these labels are often inappropriately applied to describe both aberrant drug use (reminiscent of the behaviors that characterize active abusers of illicit drugs) and phenomena related to tolerance or physical dependence. Clinicians and patients may use the word addicted to describe compulsive drug-taking in one patient and to describe nothing more than the possibility for withdrawal symptoms in another. It is not surprising that patients, families, and staff become very concerned about the outcome of opioid treatment when this term is applied.

The labels addict and addiction should never be used to describe patients who are only perceived to have the capacity for abstinence syndrome. These patients must be labeled physically dependent. Use of the word dependent alone also should be discouraged because it fosters confusion between physical dependence and psychological dependence, a component of addiction. For the same reason, the term habituation should not be used.

The psychiatric terminology applied to drug abuse and addiction, which has been codified in the DSM-IV, is also problematic.[12] The DSM-IV eschews the term addiction altogether and offers definitions of two types of substance use disorders: substance abuse and the more serious substance dependence. The criteria for substance abuse are focused on the negative psychosocial sequelae of drug use rather than the pattern of use. In contrast, a pattern of use outside of sociocultural convention is considered to be the most important criterion for abuse in other definitions (see list on Proposed Terminology for Substance Abuse).[18,19] The disparity in these definitions of abuse is confusing and underscores the challenge in labeling drug-taking behaviors in patients who are receiving potentially abusable drugs for legitimate medical purposes.

The DSM-IV criteria for substance dependence highlight psychosocial dysfunction and add the dimensions of physical dependence and tolerance. This is perhaps the most striking example of the nomenclatural problems that occur when criteria developed in substance abusers without medical illnesses are applied in a different context.[20] Most of the criteria for substance dependence disorder indicate that the term is meant to be used in a manner synonymous with addiction. The criteria of tolerance and physical dependence, therefore, are inappropriate and preclude the use of this terminology in the medically ill who may develop tolerance and physical dependence as expected consequences of therapeutic drug use.

References

1. Colliver JD, Kopstein AN: Trends in cocaine abuse reflected in emergency room episodes reported to DAWN. Drug Abuse Warning Network. Public Health Rep 106 (1): 59-68, 1991 Jan-Feb.  [PUBMED Abstract]
   
   
2. Gfroerer J, Brodsky M: The incidence of illicit drug use in the United States, 1962-1989. Br J Addict 87 (9): 1345-51, 1992.  [PUBMED Abstract]
   
   
3. Regier DA, Myers JK, Kramer M, et al.: The NIMH Epidemiologic Catchment Area program. Historical context, major objectives, and study population characteristics. Arch Gen Psychiatry 41 (10): 934-41, 1984.  [PUBMED Abstract]
   
   
4. Burton RW, Lyons JS, Devens M, et al.: Psychiatric consultations for psychoactive substance disorders in the general hospital. Gen Hosp Psychiatry 13 (2): 83-7, 1991.  [PUBMED Abstract]
   
   
5. Derogatis LR, Morrow GR, Fetting J, et al.: The prevalence of psychiatric disorders among cancer patients. JAMA 249 (6): 751-7, 1983.  [PUBMED Abstract]
   
   
6. American Psychiatric Association.: Diagnostic and Statistical Manual of Mental Disorders: DSM-III-R. 3rd rev. ed. Washington, DC: American Psychiatric Association, 1987. 
   
   
7. Bruera E, Moyano J, Seifert L, et al.: The frequency of alcoholism among patients with pain due to terminal cancer. J Pain Symptom Manage 10 (8): 599-603, 1995.  [PUBMED Abstract]
   
   
8. Dole VP: Narcotic addiction, physical dependence and relapse. N Engl J Med 286 (18): 988-92, 1972.  [PUBMED Abstract]
   
   
9. Martin WR, Jasinski DR: Physiological parameters of morphine dependence in man--tolerance, early abstinence, protracted abstinence. J Psychiatr Res 7 (1): 9-17, 1969.  [PUBMED Abstract]
   
   
10. Wikler A: Opioid Dependence: Mechanisms and Treatment. New York, NY, Plenum Press, 1980. 
    
    
11. Portenoy RK: Opioid tolerance and responsiveness: research findings and clinical observations. In: Proceedings of the 7th World Congress on Pain, 1994. 595-619. 
    
    
12. Foley KM: Clinical tolerance to opioids. In: Basbaum AI, Besson JM, eds.: Towards a New Pharmacotherapy of Pain. Chichester, NY, John Wiley and Sons, 1991, pp 181-203. 
    
    
13. Redmond DE Jr, Krystal JH: Multiple mechanisms of withdrawal from opioid drugs. Annu Rev Neurosci 7: 443-78, 1984.  [PUBMED Abstract]
    
    
14. World Health Organization.: Youth and Drugs. Geneva, Switzerland: World Health Organization, 1973. 
    
    
15. American Psychiatric Association.: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed. Washington, DC: American Psychiatric Association, 1994. 
    
    
16. Halpern LM, Robinson J: Prescribing practices for pain in drug dependence: a lesson in ignorance. Adv Alcohol Subst Abuse 5 (1-2): 135-62, 1985 Fall-1986 Winter.  [PUBMED Abstract]
    
    
17. Dai S, Corrigall WA, Coen KM, et al.: Heroin self-administration by rats: influence of dose and physical dependence. Pharmacol Biochem Behav 32 (4): 1009-15, 1989.  [PUBMED Abstract]
    
    
18. Jaffe JH: Current concepts of addiction. In: O'Brien CP, Jaffe JH, eds.: Addictive States: Research Publications-Association for Research in Nervous and Mental Disease. Vol. 70. New York, NY: Raven Press, 1992, pp 1-21. 
    
    
19. Rinaldi RC, Steindler EM, Wilford BB, et al.: Clarification and standardization of substance abuse terminology. JAMA 259 (4): 555-7, 1988 Jan 22-29.  [PUBMED Abstract]
    
    
20. Sees KL, Clark HW: Opioid use in the treatment of chronic pain: assessment of addiction. J Pain Symptom Manage 8 (5): 257-64, 1993.  [PUBMED Abstract]
    
    

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