Substance-Abuse Issues in Palliative Care
Julie R. Hamrick
Steven D. Passik
Kenneth L. Kirsh
INTRODUCTION
Chemical dependency in patients with advanced illness poses complex clinical challenges. Particularly alarming is the sharp increase in controlled prescription drug abuse in the United States in the past decade (1). Physicians and other medical staff need to be continually mindful of the potential for substance abuse and diversion in the palliative care setting. The severity of substance-related problems varies significantly: some patients exhibit minor difficult behaviors, such as escalating drug dosages without informing their physicians or using analgesics to treat symptoms other than those intended. At the other end of the continuum, some patients present to the palliative care team with a known history of, or current substance dependence on, illicit drugs or prescription medications that requires aggressive drug control on the part of the treatment team. Proper identification, assessment, and clinical management of the entire spectrum of substance-related problems are critically important for optimal treatment of patients in palliative care settings.
Clinicians must balance the obligation to be thorough in assessing potential opioid abuse or diversion with the duty to ensure that patients’ pain is not undertreated. Regulatory pressures only add to this burden, leading some physicians to believe that they must avoid being duped by those abusing prescription pain medications at all costs. Although it is tempting to reduce the clinical implications of patient behavior to dichotomous labels of “addiction” or “not addiction,” this oversimplification is not in the patient’s best interests. In fact, pain management can be adapted to address the multiple possibilities that might be behind the problematic behaviors noted in an assessment. Physicians can assert control over prescriptions without necessarily ceasing to prescribe controlled substances entirely. Although these situations invariably defy simple solutions, knowledgeable clinicians can implement strategies to simultaneously address the need for compassionate care and management of problematic drug use.
PREVALENCE
Approximately half the individuals aged 15 to 54 in the United States have used illegal drugs at some point in their lives and an estimated 6% to 15% have a current or past substance use disorder of some type (2,3,4,5,6,7). In less than a decade, sharp increases in the rate of controlled prescription drug abuse have been noted, with rates climbing by nearly 94%, from 7.8 million in 1992 to 15.1 million in 2003 (1). As a result of the high prevalence of substance abuse in the US population and the association between drug abuse and life-threatening diseases such as acquired immunodeficiency syndrome (AIDS), cirrhosis, and some types of cancer (8,9,10,11,12), patients with substance-abuse-related issues are encountered commonly in palliative care settings. In diverse patient populations with progressive life-threatening diseases, the presence of a current or past drug problem complicates the management of the underlying disease and can undermine palliative treatment. The balance between the therapeutic use of potentially abusable drugs and the abuse of these drugs must be understood to optimize care.
The rapid rise in controlled prescription drug abuse is of particular concern for the palliative care team. When misused, prescription opioids and central nervous system depressants and stimulants can be deadly. In 2002, controlled prescription drugs were implicated in 30% of drug-related emergency room deaths and in at least 23% of emergency department admissions (1). Contrary to past data suggesting that most controlled prescription drug abusers were regular or experienced users, approximately one-third of abusers in 2000 were new users of controlled prescriptions according to the data from the National Center of Addiction and Substance Abuse (1). Between the years 1992 and 2003, there has been a 225% increase in new opioid abusers, a 150% increase in new tranquilizer abusers, a 127% increase in new sedative abusers, and a 171% increase in new stimulant abusers (1). Particular regions of the country, most notably the south and west, have been hardest hit.
The growing rates of abuse of controlled prescription drugs raise questions about the prevalence of substance abuse in patient populations with cancer and how palliative care physicians can best address the needs of their patients. Despite its prevalence in the general population, substance abuse appears to be very uncommon within the tertiary care population with cancer. In a 6-month period in 2005, fewer than 1% of inpatient and outpatient consultations performed by the psychiatry service at Memorial Sloan-Kettering Cancer Center (MSKCC) were requested for substance-abuse-related issues and only 3% of patients who were referred to the psychiatry department were subsequently diagnosed with a substance-abuse disorder of any type (13). This prevalence is much lower than the frequency of substance-abuse disorders in society at large, in general medical populations, and in emergency medical departments (2,6,14,15,16). A 1983 study of the Psychiatric Collaborative Oncology Group, which
assessed psychiatric diagnoses in ambulatory patients with cancer from several tertiary care hospitals (15), also found a low prevalence of substance-related disorders. Following structured clinical interviews, fewer than 5% of 215 patients with cancer met the Diagnostic and Statistical Manual for Mental Disorders (DSM) III Edition criteria for a substanceuse disorder (17) (Table 44.1).
assessed psychiatric diagnoses in ambulatory patients with cancer from several tertiary care hospitals (15), also found a low prevalence of substance-related disorders. Following structured clinical interviews, fewer than 5% of 215 patients with cancer met the Diagnostic and Statistical Manual for Mental Disorders (DSM) III Edition criteria for a substanceuse disorder (17) (Table 44.1).
TABLE 44.1 DSM-IV diagnostic criteria for substance abuse and substance dependence | ||||||
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The relatively low prevalence of substance abuse among patients with cancer treated in tertiary care hospitals may reflect institutional biases or a tendency for patients to underreport in these settings. Many drug abusers are poor, feel alienated from the health care system, may not seek care in tertiary centers, and may be reluctant to acknowledge the stigmatizing history of drug abuse. For these reasons, the low prevalence of drug abuse in cancer centers may not be representative of the true prevalence in the cancer population overall. In support of this conclusion, the findings of a 1995 survey of patients admitted to a palliative care unit indicate alcohol abuse in more than 25% of patients (18). Additional studies are needed to clarify the current epidemiology of substance abuse and dependence in patients with cancer and others with progressive medical diseases. These patients can be adequately and successfully treated only when their substance problems are noted by staff and their needs addressed.
DEFINITIONS OF SUBSTANCE ABUSE AND DEPENDENCE
Both epidemiologic studies and clinical management depend on an accepted, valid nomenclature for substance abuse and dependence. Unfortunately, this terminology is highly problematic. The pharmacologic phenomena of tolerance and physical dependence are commonly confused with abuse and true substance dependence as defined by
the DSM-IV (Table 44.1), and the definitions applied to medical patients have been developed from experience with substance-abusing populations. The clarification of this terminology is an essential step in improving the diagnosis and management of substance abuse in the palliative care setting (Table 44.2).
the DSM-IV (Table 44.1), and the definitions applied to medical patients have been developed from experience with substance-abusing populations. The clarification of this terminology is an essential step in improving the diagnosis and management of substance abuse in the palliative care setting (Table 44.2).
TABLE 44.2 Substance-abuse definitions in the medically ill | ||||||
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Tolerance
Tolerance is a pharmacologic property defined by the need for increasing doses to maintain effects (19,20). An extensive clinical experience with opioid drugs in the medical context has not confirmed that tolerance causes substantial problems (21,22). Although tolerance to a variety of opioid effects, including analgesia, can be reliably observed in animal models (23), and tolerance to nonanalgesic effects, such as respiratory depression and cognitive impairment (24), occurs routinely in the clinical setting, analgesic tolerance seldom interferes with the clinical efficacy of opioid drugs. Indeed, most patients attain stable doses associated with a favorable balance between analgesia and side effects for prolonged periods; dose escalation, when it is required, usually heralds the appearance of a progressive painful lesion (25,26,27,28,29,30,31). Unlike tolerance to the side effects of opioids, clinically meaningful analgesic tolerance, which would yield the need for dose escalation to maintain analgesia in the absence of progressive disease, appears to be a rare phenomenon. Clinical observation also fails to support the conclusion that analgesic tolerance is a substantial contributor to the development of substance dependence.
Physical Dependence
Physical dependence is defined solely by the occurrence of an abstinence syndrome (withdrawal) following abrupt dose reduction or administration of an antagonist (19,20,32). There is great confusion among clinicians about the differences between physical dependence and true substance dependence. Physical dependence, like tolerance, has been suggested to be a component of substance dependence (33,34), and the avoidance of withdrawal has been postulated to create behavioral contingencies that reinforce drugseeking behavior (35). These speculations, however, are not supported by experience acquired during opioid therapy for chronic pain. Physical dependence does not preclude the uncomplicated discontinuation of opioids during multidisciplinary pain management of nonmalignant pain (36), and opioid therapy is routinely stopped without difficulty in the patients with cancer whose pain disappears following effective antineoplastic therapy. Indirect evidence for a fundamental distinction between physical dependence and substance dependence is even 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 (37).
Addiction
The terms addiction and addict are particularly troublesome. 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. The labels “addict” and “addiction” should never be used to describe patients who are only perceived to have the capacity for an 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 substance dependence. For the same reason, the term habituation should not be used. It is recommended that the DSM-IV (17) terms substance abuse and substance dependence be applied as appropriate.
Definitions of “substance abuse” and “substance dependence” must be based on the identification of drug-related behaviors that are outside of cultural or societal norms. The ability to categorize questionable behaviors (e.g., consuming a few extra doses of a prescribed opioid, particularly if this behavior was not specifically prescribed by the clinician, or using an opioid drug prescribed for pain as a nighttime hypnotic) as nonnormative presupposes that there is certainty about the parameters of normative behavior. In fact, even experienced pain clinicians disagree on the interpretation of varied drug-taking patterns. In a recent survey, pain clinicians expressed significant individual differences in the perception of which behaviors were the most problematic when asked to rank order a list of aberrant drug-taking behaviors (38). In general, physicians rated illegal behaviors as the most aberrant, followed by alteration of the route of delivery and self-escalation of dose.
Unfortunately, there are few empirical data in medically ill populations that define the meaning of specific drugrelated behaviors in relation to substance-use disorders or future drug abuse; as a result, the boundaries of normative behavior remain ill defined. The confusing nature of normative drug taking was highlighted in a pilot survey performed in 2000 at MSKCC, which revealed that inpatients with cancer harbor attitudes supporting misuse of drugs in the face of symptom management problems and that women with human immunodeficiency virus (at MSKCC for palliative
care) engage in such behaviors commonly (39). The prevalence of such behaviors and attitudes among the medically ill raises concern about their predictive validity as a marker of any diagnosis related to substance abuse. Clearly, there is a need for empirical data that illuminate the prevalence of drug-taking attitudes and behaviors in different populations of medically ill patients.
care) engage in such behaviors commonly (39). The prevalence of such behaviors and attitudes among the medically ill raises concern about their predictive validity as a marker of any diagnosis related to substance abuse. Clearly, there is a need for empirical data that illuminate the prevalence of drug-taking attitudes and behaviors in different populations of medically ill patients.
The core concepts used to define substance dependence also may be problematic as a result of changes induced by a progressive disease. Deterioration in physical or psychosocial functioning caused by the disease and its treatment may be difficult to separate from the morbidity associated with drug abuse. This may particularly complicate efforts to evaluate the concept of “use despite harm,” which is critical to the diagnosis of substance abuse or dependence. For example, the nature of questionable drug-related behaviors can be difficult to discern in the patient who develops social withdrawal or cognitive changes following brain irradiation for metastases. Even if impaired cognition is clearly related to the drugs used to treat symptoms, this outcome might only reflect a narrow therapeutic window, rather than a desire on the patient’s part for these psychic effects.
Definitions of Substance Dependence in the Medically III
Previous definitions that include phenomena related to physical dependence or tolerance cannot be the model terminology for medically ill populations who receive potentially abusable drugs for legitimate medical purposes. A more appropriate definition of substance dependence notes that it is a chronic disorder characterized by “the compulsive use of a substance resulting in physical, psychological, or social harm to the user and continued use despite that harm” (40). Although this definition was developed from experience in substance-abusing populations without medical illness, it appropriately emphasizes that substance dependence is, fundamentally, a psychological and behavioral syndrome. Any appropriate definition of substance abuse or dependence must include the concepts of loss of control over drug use, compulsive drug use, and continued use despite harm.
Even appropriate definitions of substance dependence will have limited utility, however, unless operationalized for a clinical setting. The concept of “aberrant drug-related behavior” is a useful first step in operationalizing the definitions of substance abuse and dependence and recognizes the broad range of behaviors that may be considered problematic by prescribers. Although the assessment and interpretation of these behaviors can be challenging, as discussed previously, the occurrence of aberrant behaviors signals the need to reevaluate and manage drug taking, even in the context of an appropriate medical indication for a drug.
If drug-taking behavior in a medical patient can be characterized as aberrant, a “differential diagnosis” for this behavior can be explored. That a patient has a true substancedependent disorder is only one of several possible explanations. The challenging diagnosis of pseudoaddiction must be considered if the patient is reporting distress associated with unrelieved symptoms. In the case of pseudoaddiction, behaviors such as aggressively complaining about the need for higher doses and occasional unilateral drug escalations indicate desperation caused by pain and disappear if pain management improves.
Alternatively, impulsive drug use may indicate the existence of another psychiatric disorder, the diagnosis of which may have therapeutic implications. Patients with borderline personality disorder can express fear and rage through aberrant drug taking and behave impulsively and self-destructively during pain therapy. Passik and Hay (41) reported a case in which one of the more worrisome aberrant drug-related behaviors, forging of a prescription for a controlled substance, was an impulsive expression of fears of abandonment, having little to do with true substance abuse in a borderline patient. Such patients are challenging and often require firm limit-setting and careful monitoring to avoid impulsive drug taking.
Similarly, patients who self-medicate for anxiety, panic, depression, or even periodic dysphoria and loneliness can present as aberrant drug takers. In such instances, careful diagnosis and treatment of these problems can at times obviate the need for such self-medication. Occasionally, aberrant drug-related behavior appears to be causally related to a mild encephalopathy, with confusion about the appropriate therapeutic regimen. This may be a concern in the treatment of the elderly patient. Low doses of neuroleptic medications, simplified drug regimens, and help with organizing medications can address such problems. Rarely, problematic behaviors indicate criminal intent, such as when patients report pain but intend to sell or divert medications.
These diagnoses are not mutually exclusive. A thorough psychiatric assessment is critically important, both in the population without a prior history of substance abuse and the population of known abusers, who have a high prevalence of psychiatric comorbidity (42,43).
In assessing the differential diagnosis for drug-related behavior, it is useful to consider the degree of aberrancy (Table 44.3). The less aberrant behaviors (such as aggressively complaining about the need for medications) are more likely to reflect untreated distress of some type, rather than substance dependence-related concerns. Conversely, the more aberrant behaviors (such as injection of an oral formulation) are more likely to reflect true substance dependence. Although empirical studies are needed to validate this conceptualization, it may be a useful model when evaluating aberrant behaviors.
EMPIRICAL STUDIES USING THE ABERRANT DRUG-TAKING CONCEPT
Several studies have investigated the usefulness of considering aberrant drug taking as occurring on a continuum. Although the studies performed to date all involve small samples, they have shown that conceptualizing aberrant drug taking in this way has important implications for clinicians. The first study examined the relationship between aberrant drug-taking behaviors and compliance-related outcomes in patients with a history of substance abuse receiving
chronic opioid therapy for nonmalignant pain. Dunbar and Katz (44) examined outcomes and drug taking in 20 patients with diverse histories of drug abuse who underwent a year of chronic opioid therapy. During the year of therapy, 11 patients were adherent with the drug regimen and 9 were not. The authors examined patient characteristics and aberrant drug-taking behaviors that differentiated the two groups. The patients who did not abuse the therapy were abusers of solely alcohol (or had remote histories of polysubstance abuse), were participating in 12-step programs, and had good social support. The patients who abused the therapy were polysubstance abusers, were not participating in 12-step programs, and had poor social support. The specific behaviors that were recorded more frequently by those who abused the therapy were unscheduled visits and multiple phone calls to the clinic, unsanctioned dose escalations, and acquisition of opioids from more than one source.
chronic opioid therapy for nonmalignant pain. Dunbar and Katz (44) examined outcomes and drug taking in 20 patients with diverse histories of drug abuse who underwent a year of chronic opioid therapy. During the year of therapy, 11 patients were adherent with the drug regimen and 9 were not. The authors examined patient characteristics and aberrant drug-taking behaviors that differentiated the two groups. The patients who did not abuse the therapy were abusers of solely alcohol (or had remote histories of polysubstance abuse), were participating in 12-step programs, and had good social support. The patients who abused the therapy were polysubstance abusers, were not participating in 12-step programs, and had poor social support. The specific behaviors that were recorded more frequently by those who abused the therapy were unscheduled visits and multiple phone calls to the clinic, unsanctioned dose escalations, and acquisition of opioids from more than one source.
TABLE 44.3 Degrees of aberrance in drug-taking behavior | ||||||
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A second study examined the relationship between aberrant drug taking and the presence or absence of a psychiatric diagnosis of substance-use disorder in pain patients. Compton et al. (45) studied 56 patients seeking pain treatment in a multidisciplinary pain program who were referred for “problematic drug taking.” The patients all underwent structured psychiatric interviews, and the sample was divided between those qualifying and those not qualifying for psychiatric diagnoses of substance-use disorders. The authors then examined the subjects’ reports of aberrant drug-taking behaviors on a structured interview assessment. The patients who qualified for a substance-use disorder diagnosis were more likely to have engaged in unsanctioned dose escalations, received opioids from multiple sources, and reported a subjective impression of loss of control of their prescribed medications.
Passik and researchers at a major cancer center (39) examined the self-reports of aberrant drug-taking attitudes and behaviors in samples of patients with cancer (N = 52) and patients with AIDS (N = 111) on a questionnaire designed for the purposes of the study. Reports of past drug use and abuse were more frequent than the present reports in both groups. Current aberrant drug-related behaviors were seldom reported, but attitude items revealed that patients would consider engaging in aberrant behaviors or would possibly excuse them in others, if pain or symptom management were inadequate. It was found that aberrant behaviors and attitudes were endorsed more frequently by the women with AIDS than by male and female patients with cancer. Overall, patients greatly overestimated the risk of substance dependence during pain treatment. Experience with this questionnaire suggests that patients both with cancer and AIDS respond in a forthcoming fashion to drug-taking behavior questions and describe attitudes and behaviors which may be highly relevant to the diagnosis and management of substance-use disorders.
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