Current Diagnosis & Treatment of Pain, 1st Edition

7. Pain & Addictive Disease

Steven D. Passik PhD

Kenneth L. Kirsh PhD

Russell K. Portenoy MD

Addiction and drug abuse are very common in the United States; 6 to 10% of the population abuses illicit drugs, 15% abuse alcohol, 25% are addicted to nicotine, and 33% of the population samples illicit drugs at least once. Because substance abuse is a risk factor for some sources of chronic pain, these problems will inevitably be seen in a sizable number of patients with chronic pain. There is no reason to believe that abuse rates would be any lower in patients with chronic pain than in the general population. Given this notion, there is an interesting phenomenon concerning the perception of opioid medications both in the United States and within the health care system. Some members of the medical community (in general, specialists in addiction) consider opioids to be a major cause of abuse, associated with dire consequences to the individual and society at large; whereas, others (usually pain specialists) view opioids as essential medications to relieve pain and suffering. Given the opposing nature of these perspectives, it is not surprising that historically there has been little communication between these two groups.

The Traditional Addiction Specialist Perspective

Specialists in addiction have defined such terms as “tolerance” and “dependence,” which are useful in nonpain settings. However, such terminology fails to address the meaning and manifestation of these phenomenon in patients treated with analgesics for painful medical disease. The perspective of addiction specialists is also based on seeing patients who have typically started opioid medications or been exposed to them solely for the purposes of recreational use. In addition, many (if not all) of these patients are vulnerable to the medications, and the addiction specialist is likely to only see the negative consequences of opioids, which can also foster the sense of these medications as being a “gateway” to illicit drug use. Thus, it is typical for these specialists to believe that exposure to the drugs will cause addiction.

The Traditional Pain Specialist Perspective

Pain management professionals have cycled through various stages in their beliefs regarding the abuse potential of opioids. The old mythology stated that addiction was so fearsome and unavoidable that opioids should be with held until patients were close to death. Luckily, a revolution in pain management, along with the use of opioids that began in oncology and spread to pain of all types, showed that this perception was false. But this myth has been replaced by another, which suggests that patients with chronic pain are somehow immune to problems of aberrant drug-taking, abuse, or diversion. These conclusions were erroneously based on questionable data, such as in the Boston Collaborative Drug Surveillance Project. In that study, the authors evaluated 11,882 inpatients who had no prior history of addiction and were administered an opioid while hospitalized; only four cases of addiction could be identified subsequently. The study focused on treatment of acute pain and was not concerned with chronic pain issues; it must be noted that the Boston Collaborative Drug Surveillance Project was not a developed study but merely a letter to the editor that well-intending professionals used as a rationale to treat more chronic pain with opioids. The potential for opioid addiction is a constant consideration in the management of acute and chronic pain; however, the criteria that define this outcome or the factors that may contribute to it are not well understood.

Thus, there has been a natural divide between these two sets of professionals. However, due to the increased media coverage of the growing abuse of prescription drugs, a new level of discourse has begun. The interaction between pain and addiction specialists has led to the beginning of a shared knowledge that enhances each other's ability to comprehend clinical phenomena and formulate questions for research.

This chapter brings together these two perspectives through an examination of the issues raised by each of two situations commonly encountered in clinical practice: the management of pain in patients with a history of opioid abuse, and the risk of opioid abuse in patients with no such history who are given opioid drugs for medical purposes. Throughout this text, an effort is made to balance the clinical imperative to provide adequate relief of pain with legitimate concerns about the consequences of opioid abuse. Opioids are the focus of this discussion because they have a unique position as both major analgesics and drugs of abuse, and thereby encourage a comprehensive examination of the issues. It should be noted, however, that many of the topics explored herein

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apply equally to other drug classes, such as the use of benzodiazepines for anxiety and other disorders.

Redefining Abuse & Addiction

Both epidemiologic studies and clinical management depend on an accepted, valid nomenclature for substance abuse and addiction. Unfortunately, this terminology is highly problematic as the pharmacologic phenomena of tolerance and physical dependence are commonly confused with abuse and addiction, as well as sociocultural considerations, which may lead to mixed messages in the clinical setting. The clarification of this terminology is an essential step in improving the diagnosis and management of substance abuse.

  1. Tolerance

Tolerance, a pharmacologic property defined by the need for increasing doses to maintain effects, has been a particular concern during opioid therapy. Clinicians and patients both commonly express concerns that tolerance to analgesic effects may compromise the benefits of therapy and lead to the requirement of progressively higher, and ultimately unsustainable, doses. In addition, the development of tolerance to the reinforcing effects of opioids, and the consequent need to increase doses to regain these effects, has been speculated to be an important element in the pathogenesis of addiction. Notwithstanding these concerns, an extensive clinical experience with opioid drugs in the medical context has not confirmed that tolerance causes substantial problems. Thus, unlike tolerance to the side effects of the opioids, clinically meaningful analgesic tolerance appears to be a rare phenomenon and is rarely the cause for dose escalation.

Clinical observation also fails to support the conclusion that analgesic tolerance is a substantial contributor to the development of addiction. It is widely accepted that addicts without a medical disorder may or may not have any of the manifestations of analgesic tolerance. Occasionally, a patient treated with opioids may show signs of analgesic tolerance but typically does not show signs of abuse or addiction.

  1. Physical Dependence

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

There is great confusion among clinicians about the differences between physical dependence and addiction. Physical dependence, like tolerance, has been suggested to be a component of addiction, and the avoidance of withdrawal has been postulated to create behavioral contingencies that reinforce drug-seeking behavior. 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, and opioid therapy is routinely stopped without difficulty in patients with cancer whose pain disappears following effective antineoplastic therapy. Furthermore, 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.

New Definitions of Abuse & Addiction for the Medically Ill

  1. Abuse

Various definitions of abuse that include the phenomena related to physical dependence or tolerance are not applicable to patients who receive potentially abusable drugs for legitimate medical purposes. A differential diagnosis should be explored if questionable behaviors occur during pain treatment (Table 7-1). A true addiction is only one of several possible explanations but is more likely when behaviors such as multiple unsanctioned dose escalations and obtaining opioids from multiple prescribers occur.

The diagnosis of pseudoaddiction must also be considered if the patient is reporting distress related to unrelieved symptoms. Behaviors such as aggressively complaining about the need for higher doses or occasional unilateral drug escalations may be indications that the patient's pain is undermedicated. Clearly, the diagnosis of addiction is not tenable if pain control eliminates behaviors that would otherwise be considered to reflect loss of control, compulsive use, and continued use despite harm. Aberrant drug-related behaviors may not be infrequent occurrences in the treatment of nonmalignant pain.

Table 7-1. Differential Diagnosis of Aberrant Drug-Taking Attitudes and Behavior.

· Addiction

· Pseudoaddiction (inadequate analgesic)

· Other psychiatric diagnoses
   – Chemical coping
   – Encephalopathy
   – Borderline personality disorder
   – Depression
   – Anxiety

· Criminal intent

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Impulsive drug use may also indicate the existence of another psychiatric disorder, the diagnosis of which may have therapeutic implications. For example, patients with borderline personality disorders may be categorized as exhibiting aberrant drug-taking behaviors if they are using prescription medications to express fear and anger or improve chronic boredom. Similarly, patients who use opioids to self-medicate symptoms of anxiety or depression, insomnia, or problems of adjustment may be classified as aberrant drug takers. Occasionally, aberrant drug-related behaviors appear to be causally related to mild encephalopathy, with confusion regarding the appropriate therapeutic regimen. Problematic behaviors rarely imply criminal intent such as when patients report pain but intend to sell or divert medications. These diagnoses are not mutually exclusive and a thorough psychiatric assessment is vitally important in an effort to categorize questionable behaviors properly in both the population without a prior history of substance abuse and the population of known substance abusers who have a higher incidence of psychiatric comorbidity.

  1. Addiction

Until recently, all accepted definitions applied to the assessment of addiction had been developed by addiction specialists. These definitions emphasize that addiction is a psychological and behavioral syndrome in which there is drug craving, compulsive use, a strong tendency to relapse after withdrawal, and continued use despite harm to the user or those around him or her. Some of these definitions highlight the development of tolerance or physical dependence in the development of addiction. Although widely accepted, the specifics must be interpreted cautiously if the drug of abuse may be a legitimate therapy for a medical disorder.

According to a recent definition jointly endorsed by professional societies for pain and addiction in the United States, “addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors…. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.” This definition does not reference phenomena related to tolerance or physical dependence but rather, focuses on behavior as the relevant assessment for the diagnosis of addiction. Craving may involve rumination about the drug and an intense desire to secure its supply. Compulsive use may be indicated by persistent or escalating consumption of the drug despite physical, psychological, or social harm to the user.

Categories of Substance Abusers

Patients with a history of opioid abuse can be divided into three categories that may predict some of the problems encountered during pain treatment; these categories include the following:

  1. Patients with a remote history of opioid substance abuse.
  2. Patients with a history of opioid abuse who are currently undergoing methadone maintenance treatment.
  3. Patients actively abusing opioid drugs.

Other relevant groups may include those with a remote or present history of addiction to alcohol, nonopioid illicit drugs (eg, cocaine), or nonopioid prescription drugs (eg, benzodiazepines). These distinctions help identify patients at risk for management problems, and this, in turn, may facilitate the assessment process and suggest approaches to therapy.

Unfortunately, there have been no adequate studies to confirm the existence of meaningful differences among these groups or specifically assess the needs and problems posed by each during therapy for pain. Case reports have been helpful in defining the range of concerns and have been particularly useful in highlighting the observation that even a remote history of abuse can stigmatize a patient and complicate pain treatment. Nonetheless, generalizations developed from clinical experience may fail to prepare the clinician for the vagaries of practice, where the experience of pain itself, or other facets of the disease causing the pain, may alter responses in an unpredictable way. They cannot substitute for a comprehensive assessment of each case.

Principles of Pain Assessment

An optimal approach to therapy depends on a comprehensive assessment that clarifies the organic and psychological contributions to the pain and characterizes associated problems that may also require treatment. These associated problems may themselves be medical, psychological (including disorders of personality or affect or profound behavioral disturbances), social, or familial. A history of substance abuse is one such consideration.

Categories of Patients with Pain

Patients with pain can be categorized in several clinically meaningful ways. Some distinctions are particularly relevant to the selection of treatment approaches.

First, patients may be deemed to have acute monophasic pain. These are the most common pains and are acute and self-limited. Most are never evaluated by physicians and demand no therapy beyond simple measures taken by the individual, although some may require clinical intervention. Notwithstanding data documenting the frequent undertreatment of these syndromes, the short-term administration of opioid drugs is widely considered

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to be medically appropriate treatment for acute severe pain.

The second category, recurrent acute pain, is also extremely prevalent. These disorders also range in severity and need for clinical intervention (eg, headache, dysmenorrhea, sickle cell anemia, inflammatory bowel disease, and some arthritides or musculoskeletal disorders).

The third category is chronic pain associated with cancer. Opioid therapy is considered to be the major therapeutic approach to patients with cancer pain.

Chronic pain associated with progressive nonmalignant medical disease is the fourth category. Like pain due to cancer, other pain syndromes are related to progressive medical illness associated with poor prognosis. A recent study, for example, demonstrated striking similarities between cancer and AIDS in the prevalence, characteristics, and impact of pain.

The fifth category is chronic pain associated with a nonprogressive organic lesion. Many patients have an overtly painful organic lesion that is not life-threatening but is presumed to be adequate to explain the pain. Although psychological processes again can have a profound impact on symptoms and associated functional disturbances, the pain is perceived to be commensurate with the underlying organic condition.

The final category includes patients with chronic non-malignant syndromes. A large group of patients experience pain or associated disability that is perceived by the clinician to be excessive for the degree of organic disease present. Although these pains have been termed “idiopathic,” this term usually does not connote the existence of psychiatric comorbidity and disability in the same way. Overall, the array of labels should not obscure the key point, which is that chronic pain may reflect a complex interaction between biomedical factors and psychological factors, and that each patient requires an astute assessment of all these factors as well as comorbidities.

Management of Pain in the Substance Abuser

Regardless of the population in question, there are important differences between the relatively brief use of opioids to manage acute pain and the long-term use to treat patients with persistent pain. The therapeutic use of opioids in the patient with a history of substance abuse raises additional issues in both clinical settings.

  1. Chronic Pain

The role of opioid therapy in patients with a history of substance abuse and chronic pain has traditionally varied with the distinction between cancer-related pain and nonmalignant pain. Opioids are accepted in the management of cancer pain, and management of this condition in patients with a history of substance abuse requires pharmacologic expertise equal to that applied to similar patients without this history. Opioids have generally been discouraged in other populations with chronic pain; this is particularly true when the patient's pain is complicated by a history of substance abuse.

From a critical perspective, this distinction between cancer pain and nonmalignant pain may be difficult to rationalize. Nonmalignant pain syndromes are extraordinarily diverse, and even a simple classification identifies other large groups of patients with chronic, severe pain due to progressive medical disorders that are similar to cancer in terms of prognosis and functional outcomes but are not neoplastic. It is particularly difficult to justify the view that opioids are the first-line drug for cancer pain but are relatively contraindicated in such pain syndromes as AIDS, sickle cell anemia, hemophilia, inflammatory bowel disease, and others. Similar concerns may arise in attempting to discern the medical rationale for the conventional rejection of opioid drugs in other chronic pain populations, some of which may, like the cancer population, experience pain as a consequence of tissue injury or neuropathic lesions, or experience chronic pain without the development of psychiatric comorbidity or disability.

  1. Other Considerations in the Substance Abuser with Chronic Pain

Although the basic approach to the management of chronic pain should apply equally to all patients, including substance abusers, it is nonetheless true that problems may be encountered in the latter population that distinguish it from others. As noted previously, clinical experience suggests that there may be salient differences among those with remote history of addiction, those currently treated in methadone maintenance programs, and those actively abusing opioids or other drugs. A small retrospective study suggested that all three groups were at relatively high risk for inadequate pain management, but only those who were actively abusing could not reliably achieve adequate symptom control once they were treated aggressively by pain service personnel. The major issues encountered during the treatment of each of these groups can be summarized in the following sections.

  1. Patients with a remote history of substance abuse—

Although clinical experience suggests that patients with a remote history of substance abuse respond appropriately to opioids, the empiric data in support of this conclusion are meager. From a theoretical perspective, it could be speculated that the same genetic, psychological, and situational factors that predisposed persons to the addiction syndrome initially could increase the risk of aberrant drug-taking behavior in patients administered opioids for therapeutic purposes. The failure to observe these outcomes in practice suggests that the factors that ultimately combined to eliminate the abuse

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behaviors-as well as with the situational changes associated with the diagnosis and treatment of the pain syndrome-may reduce the likelihood of iatrogenic addiction.

It has been observed clinically that some patients with chronic pain who have a remote history of substance abuse are poorly compliant with opioid therapy due to a persistent fear of these drugs. Thus, the optimal management of the patient with chronic pain and remote history of addiction must incorporate careful, ongoing assessment of drug-taking behavior and the recognition that successful treatment may be compromised both by the attitudes of practitioners, whose overconcern about addiction can distort analgesic management, and the attitudes of the patient, whose behavior may implicitly or explicitly endorse the concerns of the staff or result directly in undertreatment. Education of the staff and the patient may limit the adverse consequence of these attitudes and thereby improve pain management.

  1. Patients in methadone maintenance programs—

Like those persons who have a remote history of substance abuse, patients receiving methadone maintenance are at high risk for undertreatment of chronic pain. In this population, negative attitudes held by the medical staff may combine with some degree of tolerance to opioid analgesics to limit the efficacy of therapy. If persistent pain reports are interpreted as a manipulative attempt to obtain opioids for purposes other than analgesia, the therapeutic relationship will become conflicted; the clinician's goals for analgesia will be superseded by the desire to prevent drug abuse. This concern is, of course, legitimate if aberrant drug-taking behaviors return in a patient. If “drug-seeking” reflects only the need for pain relief, however, undertreatment will result from the failure to respond.

The failure to recognize the need for higher starting doses may lead to initial problems with the management of chronic pain in methadone-treated patients. Patients who have not received an opioid for pain before, but have been receiving methadone for some time, may require starting doses substantially higher than those conventionally used at the initiation of chronic pain therapy. In a rather typical scenario, a patient is given an opioid at a dose perceived by the clinician to be effective, but the patient gains no relief and voices a complaint; the persistence of pain, perhaps now combined with a sense of mistrust or acrimony, is interpreted as evidence of addiction, and the patient is managed by the further withholding of opioids rather than by aggressive upward dose titration. This, of course, further undermines the therapeutic alliance and reduces the likelihood of successful treatment.

It is a common misconception that the use of methadone as an analgesic for pain can mirror its use in the therapy of opioid addiction. In pain management, doses must be titrated according to patient response; there is no predefined appropriate dose range. Equally important, the single daily dose that is sufficient for the management of addiction is almost never adequate to sustain analgesia throughout the day. Extensive clinical experience indicates that analgesia usually requires at least three doses per day. Many patients actually achieve more stable analgesia with four or six doses per day, an observation supported by studies that demonstrate a duration of analgesia that is typically much briefer than would be expected from the half-life of this drug.

  1. Active drug abusers—

The view of opioid therapy in patients with a remote history of drug abuse and those in methadone maintenance is not applicable to the small number of patients in whom chronic pain develops while actively abusing opioids or other drugs. Anecdotally, pain management in many of these patients is complicated by substantial psychopathology and adverse situational factors. The degree of psychopathology may be severe enough that a useful therapeutic alliance is impossible, and both the veracity of the complaints and compliance with prescribed therapies become major problems.

Careful assessment is again critical to appropriate management. Clear-cut abuse behaviors (including continued use of illicit drugs) must be distinguished from other behaviors (such as frequent emergency department visits) that may be more difficult to interpret. Although both types of behaviors may reflect inadequacy of pain treatment as well as psychological dependence on the drug, the former is clear-cut abuse, which cannot be condoned, whereas the latter potentially may indicate a lesser degree of psychopathology and a desire to remain in the medical setting for the treatment of a pain problem. The specific psychopathology of these patients must be carefully evaluated. Sociopathy is relatively common among the addict population, and to the extent possible, the clinician should attempt to determine whether sociopathic behaviors have been characteristic of the patient prior to the diagnosis of chronic pain. Straightforward questioning about illegal practices may yield surprisingly frank answers, from which an assessment of these behaviors can be made. Although it must be emphasized that the studies needed to clarify these issues have not been performed, it is likely that the risk of management problems during analgesic therapy correlates generally with the degree of psychopathology, and more specifically with the severity of sociopathic proclivities.

In some cases, efforts to implement a simple and effective pharmacologic regimen for pain may have to be sacrificed in lieu of interventions designed to maintain therapeutic control. Virtually all patients require greater frequency of monitoring and strict attention to the assessment of efficacy, side effects, and drug-taking

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behavior. Some clinicians favor the use of a written agreement that is kept in the medical record and both defines the medication regimen and explicitly states the responsibilities of both the patient and clinician. An example of such an agreement can be found at http://www.painmed.org/productpub/statements/pdfs/opioid_consent_form.pdf. These guidelines should include specific reference to the methods that will be used to renew prescriptions as well as the response that a report of lost or stolen drugs will generate. It may be useful to establish a rule that lost or stolen drugs must be reported to the police and that documentation of this must be provided. When such circumstances arise, prescribing drugs that have relatively low street value, such as methadone, may be more appropriate than prescribing other drugs, such as hydromorphone, for which there is greater demand among street addicts.

For some patients, the cardinal principle of opioid dose titration simply cannot be accommodated due to demands that are perceived to be inappropriate. Limits must be set based on the clinician's assessment of the risks and benefits in this difficult situation. In rare cases, the persistence of severe pain in the setting of intractable management problems suggests the immediate use of some approaches, such as neurolytic techniques, that generally are considered only after an optimal opioid therapy fails.

In all of this decision-making, the dictates of humane and compassionate care should support a bias that patients generally are to be believed. Factitious pain complaints and malingering appear to be rare among patients who are not actively abusing drugs (including those with a remote history of addiction) and probably are uncommon among active abusers who have cancer. Rather, most substance abusers are like other patients with pain, whose symptoms reflect some combination of ongoing nociception and psychological distress. Unless the evidence in support of malingering is compelling, the clinician is better served by avoiding an argument about the “reality” of the pain and focusing instead on the possibility that pain may be profoundly influenced by psychological factors, possibly including psychological dependence on opioids. It is more productive simply to believe the patient's complaint and thoughtfully assess the degree to which it can be explained by physical and psychological determinants. In keeping with this view, it may be postulated that the premorbid psychopathology of the addict predisposes to a greater psychological contribution to pain than is usually observed in the cancer population. This, too, must be evaluated in future research.

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