Tolerance and physical dependence are predictable consequences of chronic opioid use, but they do not necessarily equal addiction (Newman, 1983). Numerous clinical, epidemiologic, and pharmacologic studies now suggest that cancer patients may become tolerant and physically dependent on opioids if therapeutic doses are prescribed for several weeks. However, very few patients develop the loss of control and compulsive use patterns that allow continued use of opioids (and other prescribed or illicit substances) despite medical, social, legal, or emotional harm. This sort of behavior, more than tolerance and physical dependence, characterizes and defines addiction (Portenoy and Payne, 1992).
An adequate assessment of the cause of pain is essential to the optimal treatment of the opioid addict with cancer. As with other cancer populations, specific antitumor treatments are indicated as the single best method of pain relief. Frequently, however, adequate analgesia has to be established before diagnostic studies and medical or surgical treatments can proceed. The appropriate management of the medical condition often decreases the requirements for opioids. Optimal pain treatment is essential to preventing the syndrome of "pseudoaddiction" (Weissman and Haddox, 1989) because inadequate pain management will invariably produce the manipulative behavior that the clinician wants to avoid.
Although not clearly substantiated by prospective clinical studies, it is common practice to make distinctions among (1) addicts who are actively abusing opioids and illicit narcotics.at the time of their treatment for acute pain, (2) former addicts who no longer abuse drugs, and (3) addicts in methadone maintenance (Fultz and Sonay, 1975). Patients actively abusing heroin or prescription opioids (and those on methadone maintenance) should be assumed to have some degree of pharmacologic tolerance, which will be reflected in a need for higher-than-usual starting doses and dosing intervals shorter than those generally recommended in the nonaddicted population. Furthermore, because patients who are actively abusing drugs often manifest psychological disorders that influence pain perception (e.g., anxiety and depression), the treatment of concomitant psychiatric disturbances is often necessary and usually requires the consultation of experienced psychiatric clinicians. Patients with cancer who have abused drugs in the past (but who are not current abusers) or who are participating in methadone maintenance programs may have a higher degree of opioid tolerance than the general population. Among these patients, it is useful to anticipate that significant anxiety may accompany the stress of medical illness and acute pain and be manifested in a reappearance of drug-abuse behaviors.
The use of opioid agonist-antagonist compounds in known or suspected active opioid addicts is absolutely contraindicated. Not only do these drugs have ceiling effects to their analgesic efficacy, and are therefore inappropriate for severe pain, but they-may also precipitate withdrawal and increased pain in physically dependent patients. Likewise, nonopioid analgesic modalities should not be substituted for opioid analgesics to treat severe pain in patients who are suspected or known abusers of illicit substances. Tolerance to opioid analgesics decreases the duration of effective analgesia (Houde, 1979); therefore, "tolerant" patients require more frequent dosing than do nontolerant patients. For example, morphine, which has an average analgesic duration of 3 to 4 hours, may produce only 1 to 2 hours of pain relief in an opioid addict with a large degree of tolerance.
Paradoxically, PCAs are being used with increasing frequency when rapid titration of intravenously administered opioids is required in this population. Although it would seem that the administration of opioids could not be entrusted to an addicted individual, in fact, it has its advantages: With the appropriate prescription of doses, lock-out intervals, and instruction to the patient, this method of administration may reduce the confrontation and conflict inherent in clinician-administered analgesia. Opioid addicts may report a euphoric feeling or "high" coincident with an intravenous bolos injection of opioids, which presumably reinforces the need to self-administer drugs (Jaffe, 1985). Nevertheless, intravenous opioids can be used effectively (see below).
Appropriate PCA boles doses and "lock-out" periods (i.e., the time that should elapse between the administration of one dose and the next) should be selected. The opioid addict may be easily underdosed and experience poor pain relief if the degree of the patient's tolerance is not accurately assessed. The commonly published "lock-out" times and starting boles doses are inappropriate for most opioid addicts and indeed for many patients whose prior opioid experience is such that they manifest opioid tolerance; in fact, the typical published parameters apply to the postoperative population of relatively opioid-naive patients. The prolonged self-administration of morphine to cancer patients with acute recurrent pain caused by oral mucositis after bone marrow transplantation did not increase the risk for overmedication or addiction (Chapman and Hill, 1989), and compared with standard intravenous infusion, PCA decreased the requirements for morphine by 53 percent (Hill, Chapman, Kornell, et al., 1990). Although those patients were not addicts, the data nevertheless support the argument that PCA of intravenous morphine for pain does not invariably lead to ever-escalating dose requests.
Patients who are maintained on methadone for the treatment of addiction may also be treated with this agent for pain, if it is administered frequently enough. In this setting, methadone is useful in that the patient's dose may be easily tapered back to the level of the maintenance dose after the painful episode has been treated. In reality, however, most methadone maintenance programs do not have the flexibility to change the rules for individual patients to allow increases in the daily methadone dose or to increase the dosing frequency beyond once or twice a day. Unfortunately, then, the treatment of pain with methadone in this manner usually has to take place outside of the typical maintenance program.
For acute focal pain syndromes, regional anesthetic approaches such as somatic and sympathetic nerve block should be considered, unless contraindicated. These approaches are generally unsafe in patients who are septic, who have coagulopathy, or-who are acutely confused and uncooperative. Nonpharmacologic methods can be useful adjuncts in the treatment of pain in this population.
One common characteristic of patients who are actively abusing opioids is a failure to set limits on their drug-seeking behavior, even in the presence of liberal uses of opioids for pain management. The clinician should discuss expectations and define limits of acceptable and unacceptable behaviors with the patient. The use of drug infusion pumps with security locks (available on almost all PCA pumps) should prevent dose , escalation beyond what the clinician prescribes. If oral opioid analgesics are being administered, patients should be told that their ingestion will be witnessed and that routine precautions, such as searching the room for hidden pills or signs of hoarding, will be taken.
In the outpatient setting, clearly stated, written rules should cover prescription renewals, the procedure to be followed with lost or stolen prescriptions or medications, and procedures to ensure that only one clinician is prescribing analgesic medications. Prescription theft or forgery should lead either to the patient~s admission to the hospital for continuation of opioid therapy, if still required, or to withdrawal of the therapy and referral to an appropriate drug treatment program, if opioid therapy for pain is no longer required. The patient should be seen frequently--daily, if necessary--and a limited quantity of opioids should be prescribed. In some States, the prescription of opioids to a patient known to be a "habitual user" is either unlawful or an "addict" must be reported to the State's regulatory agencies.
These general guidelines allow the clinician and the patient to establish behavioral expectations, which may be the only way to manage humanely. Patients with pain and substance abuse disorders require interdisciplinary assessment and care. These patients are generally not well managed by the traditional medical models of oncologic care, because the issues of pain management and substance abuse treatment together are almost always beyond the competence of a single clinician or clinical service and may often produce directly conflicting goals for treatment. On the one hand, for example, the traditional method of opioid addiction treatment is to detoxify the patient and provide pharmacologic and psychological therapies to maintain abstinence. On the other hand, in treating the addict with cancer-related pain, the avoidance of opioids is usually unacceptable, because there are few alternatives for effective pain treatment. However, the pain specialist usually has little ability or training to assess fully the behaviors manifested by addicts, particularly those actively amusing drugs. There is no obvious solution to this paradox, but clearly, clinical research is needed to develop a model for the care of the addict with pain that allows flexibility of traditional concepts of substance abuse and pain management and provides a mechanism that effectively integrates both disciplines.
Legal Regulation of Opioids
Cost and Reimbursement for Pain Management
The WHO Ladder
PAIN IN SPECIAL POPULATIONS
MONITORING THE QUALITY OF PAIN MANAGEMENT