Opioid Tolerance and Dependence

1. Tolerance to a drug is defined as the failure of a steady dose of the drug over time, to sustain the desired pharmacological effect, i.e., the need to increase the drug dosage to maintain the original pharmacological effect. Tolerance can occur with a wide variety of drugs, including opioids. Tolerance to the analgesic effects of opioids occur slowly, and some clinicians think it does not occur at all in cancer patients whose pain intensity remains stable. If pain seems to get rapidly out of control and large doses are required to bring the pain back under control, the pain intensity is probably increasing because of progression of the cancer.

2. Physical dependence on a drug simply means that a patient who has received an opioid for a significant period of time will have a withdrawal reaction (abstinence reaction) if the drug is abruptly withdrawn or if a narcotic antagonist, such as naloxone is administered. This condition should not be equated with "addiction." Addicted patients may be physically dependent on a drug, but physically dependent patients are not necessarily addicted to a drug. Physical dependence is a normal physiological response and should be anticipated in patients whose pain disappears and who must then be withdrawn from opioids. To avoid a withdrawal reaction, the opioid dose should be gradually reduced. The opioid can be given p.r.n. to treat the withdrawal symptoms, allowing the patient to slowly taper the dose.

3. Addiction (Psychological dependence) is a term and condition that has only social determinants. Individuals addicted to drugs make the possession and use of drugs the paramount purpose of their lives. Addicts readily sacrifice all their moral and ethical values for drugs. They are willing to sacrifice resources, money, social position, job, pleasure of eating, pleasure of sex, freedom from jail, and, finally, life itself to drugs. This picture is quite different from that of the cancer patient in pain who seeks drugs for the relief of his or her pain. It is rare that someone turns to drug abuse when introduced to an opioid for medical reasons.

Unfortunately, our society does not distinguish between the legitimate and illegitimate uses of opioids. Therefore, any use of them is considered bad, no matter what the reason. Patients unrelieved of pain who request, or insist upon, adequate control of their pain are often declared morally inferior persons, persons with weak characters, or even drug abusers by physicians and other health care providers. This reaction should be guarded against.

The following is taken verbatim from the Handbook of Cancer Pain Management prepared by Weissman, Burchman, Dinndorf, and Dahl for the Medical College of Wisconsin and the University of Wisconsin Medical School in conjunction with the Wisconsin Cancer Pain Initiative and the World Health Organization. It describes the condition of "pseudoaddiction":

"Opioid pseudooddiction " is a common iatrogenic syndrome in which patients develop certain behavioral chraracteristics of psychological dependence as a consequence of inadequate pain treatment. This may occur as a result of 1) prn dosing during periods of continuous pain and/or 2) the use of dosing intervals which are greater than the duration of action of a given analgesic and/or 3) the use of insufficiently potent analgesics. Patients with this syndrome must continually demonstrate their need for analgesics and are often described as difficult patients, chronic complainers and/or "addicts ". Patients will often resort to bazaar or dramatic behavior- (acting out) in an attempt to prove their pain is real so that analgesics will be administered. Consequences to the patient if this syndrome is not recognized and treated include a loss of trust in the health care team and feelings of isolation, fear and anger. Treatment involves breaking the vicious cycle of mistrust, and realization by the health care team that psychological dependence (addiction) should not be a consideration in deciding the proper dose and schedule of opioids. Specific measures include 1) establishing trust between patient, nurse and physician that pain can and will be controlled, 2) using scheduled ("around the clock ") analgesics of sufficient potency to provide adequate analgesia, 3) using oral drugs whenever possible and 4) frequent reassessment of the pain and level of analgesia.

Note: Short acting opioids (morphine, hydromorphone, oxycodone and codeine) are frequently prescribed at an ineffective dosing interval of every 6-8 hours in the mistaken belief that this will prevent or delay the onset of tolerance, physical, or psychological dependence. As noted above, this prescribing pattern will lead to undertreatment of the pain and potentially cause the behavior pattern seen in cases of "pseudoaddictionî."