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DAVID E. JORANSON, MSSW; CHARLES S. CLEELAND, PhD; DAVID E. WEISSMAN, MD; AARON M. GILSON, MS
Overview: The authors surveyed medical board members to determine their views on the use of opioids for the treatment of chronic cancer pain and also chronic non-malignant pain. Before presentation and discussion of the survey results, the authors provide: 1) an overview of the problem of cancer pain, 2) a review of the key role of opioid therapy in the management of cancer pain, 3) a brief analysis of controlled substances law in relation to the use of opioids to treat intractable pain, and 4) a discussion of the impediments that prevent optimal management of cancer pain with opioid analgesics, such as fear of addiction.
I. THE PROBLEM OF PAIN IN CANCER
Cancer continues to be a major cause of death and disability in the United States. According to the American Cancer Society, approximately 520,000 people will die of cancer in 1992, over one million new cases will be diagnosed. About 83 million individuals now living will develop cancer, and three out of four families will be affected. Improvements in cancer treatment and early detection have increased the survival rate and have lengthened the time that people live with cancer (American Cancer Society 1992).
It is estimated that 60-90% of patients with advanced cancer will experience significant pain (Daut and Cleeland 1982; Cleeland 1984; Foley 1985; Peteet et al. 1986; Donovan, Dillon, and McGuire 1987; Greenwald, Bonica, and Bergner 1987; Portenoy 1989). In the past, pain was typically associated with end-stage cancers, but it is now recognized that significant pain can be present at any stage and may be present for long periods of time.
Unrelieved pain can destroy the quality of life for people with cancer and their families (Cleeland 1984) and may even lead to suicide (Levin, Cleeland, and Dar 1985; Breitbart 1990). As pain becomes severe, it interferes with essential aspects of functioning, such as movement, appetite, sleep, emotional well-being, and relationships (Ferrell, Wisdom, and Wenzl 1989). Relief of pain can bring remarkable improvements in the quality of life for people who have cancer.
Tragically, cancer pain is often under-treated. It has been estimated that one-half to three-quarters of cancer patients with pain are inadequately treated and that nearly 25% of all cancer patients die with severe unrelieved pain (Daut and Cleeland 1982). One analysis of 11 published reports covering nearly 2000 patients in non-hospice settings estimated that 50-80% did not have adequate pain control (Bonica 1985). In a study sponsored by the Eastern Cooperative Oncology Group (ECOG), patients with recurrent or metastatic cancer from 15 cancer centers were surveyed about the presence, severity, and control of pain (Hatfield et al. 1991). Sixty-one percent of the sample had pain. Forty percent of those with pain rated it as significant (i.e., greater than 5 on a 0 to 10 scale). No patient in this sample was reported to be receiving morphine or a morphine-like opioid, as is recommended by the World Health Organization (WHO 1986) and the American Pain Society (APS 1989). These and other studies indicate that adequate pain control is not being achieved in a significant portion of patients, and that patients often do not receive analgesics to match the severity of their pain.
Is significant pain with cancer inevitable? No. The majority of patients can obtain pain relief if available drug and nondrug treatments are used property. Foley (1985) estimates that pain can be well-controlled for more than 85% of all cancer patients. Studies of the World Health Organization's simple oral analgesic protocol indicate that 70% to 90% of cancer patients' pain is relieved when the protocol was followed (Takeda 1987; Ventafridda et al. 1987).
II. DRUG THERAPY FOR CANCER PAIN: THE ROLE OF OPIOID ANALGESICS
Cancer pain can often be relieved by treatment with chemotherapy, hormonal therapy, surgery, radiotherapy, nerve blocks, psychological techniques, or a combination of these. However, the mainstay of chronic cancer pain management is opioid therapy. During the past 20 years there have been numerous important advances in the understanding of pain and opioid pharmacology. The phenomena of opioid tolerance, physical dependence, and psychological dependence ("addiction") have been clarified (APS 1989), and new drug formulations have increased the availability of different analgesic modalities to treat cancer pain (Foley 1985). Drugs used to treat cancer pain include non-opioids, opioids, and adjuvant drugs. Cancer pain can be managed by physicians with varied training. In addition to the oncology specialist, cancer pain may be managed by general internists, family practice physicians, anesthesiologists, and others. General principles of analgesic management of cancer pain are listed in Table 1.
A careful assessment of pain and pain history should
be obtained in each case.
| Table 1. General principles of analgesic therapy for
cancer pain.
1. Use oral drugs whenever possible. 2. Base the initial analgesic on the patient's report of pain. 3. Administer drugs around-the-clock rather than p.r.n. (as needed) for continuous pain syndromes. 4. Anticipate side effects; treat them aggressively. 5. Reevaluate the patient's report of pain frequently. 6. Ensure a continuous supply of analgesics. |
Non-opioids such as aspirin, acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) are effective for the treatment of mild pain. NSAIDs are preferred for the pain of bone metastases, while acetaminophen is used in cases where thrombocytopenia or other bleeding risks exist. The non-opioids all have an analgesic ceiling; above a certain dose no further analgesic activity is to be expected.
Opioid Analgesics
Opioid analgesics are indicated when pain is not adequately controlled by non-opioids. Obtaining a careful pain history is important before using opioids to determine baseline respiratory, renal and hepatic function, and whether the source of pain is nociceptive or neuropathic. Nociceptive pain (e.g., pressure on the nerve endings from a tumor) is usually responsive to opioids while neuropathic pain (e.g., direct damage to the nerves) has generally been regarded as relatively unresponsive. However, the use of opioids in neuropathic pain, including chronic non-malignant pain syndromes, is a subject of research and vigorous discussion in the medical and scientific community (Portenoy and Foley 1986; Max et al. 1988; Portenoy, Foley, and Inturissi 1990; Dubner 1991; Max 1991; Turk and Brody 1991).
Opioids of the morphine-agonist type, including morphine, hydromorphone, oxycodone, codeine, meperidine, methadone, levorphanol, fentanyl, and propoxyphene, all share certain pharmacologic features (Weissman et al. 1992). First, these drugs can be interchanged using equianalgesic doses to obtain equipotent analgesia. Second, unlike the nonopioids, there is no ceiling dose for many opioids as long as side effects become tolerable. Increasing pain is usually indicative of worsening cancer and can usually be treated successfully by increasing the dose of opioid until pain is relieved or side effects are intolerable. Finally, because of tremendous variation in drug absorption, metabolism and the individual nature of the pain experience, there is no standard opioid dose. What is listed in textbooks as a "standard dose," such as 10 mg of morphine or 2 mg of hydromorphone, should instead be thought of as a starting dose when dealing with cancer pain.
Although most cancer pain can be relieved with modest doses of opioids (e.g., less than 300 mg/day of parenteral morphine), some patients will need extremely high doses to control their pain (Coyle 1989). Escalation of dose is possible because continual pain acts as a stimulus to respiration. Depending on the specific circumstances, dose escalation may be managed in an inpatient or outpatient setting.
Physicians should consult analgesic principles and guidelines (see following
box) for more detailed information about pain management, including assessment
and monitoring, calculation of equianalgesic doses, dose escalation, contraindications,
and management of side effects.
|
Clinical Practice Guideline. Acute Pain Management: Operative or Medical Procedures and Trauma. U.S. Dept. Of Health and Human Services, 1992. Obtain by calling (800) 358-9295. Handbook of Cancer Pain Management (3rd edition). The Medical College of Wisconsin and the University of Wisconsin Medical School in conjunction with The Wisconsin Cancer Pain Initiative, 1992. Obtain by writing the Wisconsin Cancer Pain Initiative, 1300 University Ave., Room 3676, Madison, WI 53706; price is $3.00. Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer Pain: A Concise Guide to Medical Practice (3rd edition). American Pain Society, 1992. Obtain by calling the American Pain Society (708) 966-0050. Cancer Pain Relief. World Health Organization, 1986. Obtain from WHO Publications Center, USA, 49 Sheridan Ave., Albany, NY 12210. McGiverny, W.T. and Crooks, G.M., 1984. The care of patients with severe chronic pain in terminal illness. The Journal of the American Medical Association, 251(9):1182-1188. |
Mild to moderate pain that is not relieved by NSAIDS alone is usually treated with fixed-dose combination products that contain codeine or oxycodone with aspirin or acetaminophen. These drugs have analgesic activity for three to four hours. The dose of combination drugs can be escalated until the potential for side effects (tintinitus, gastrointestinal pain, hepatic toxicity, etc.) from the non-narcotic agent is reached. If pain is not well-controlled at that dose level, using a single entity opioid is indicated. Oxycodone appears to be more efficacious than was previously appreciated because it was not studied as a single entity drug.
Moderate to Severe Pain
Morphine has been designated by the World Health Organization as the preferred analgesic for moderate to severe cancer pain (WHO 1986). Morphine is available in numerous formulations including tablet and liquid short-acting preparations (analgesic activity of 3-4 hours), long-acting preparations (analgesic activity of 8-12 hours), rectal suppositories and parenteral dosing formulations for intravenous, subcutaneous, intramuscular, spinal or ventricular administration.
Hydromorphone is a good alternative to morphine, available in oral, rectal, and parenteral preparations. Hydromorphone has a similar duration of analgesia as morphine (3-4 hours), but is four to six times more potent than morphine. Levorphanol and methadone are also reasonable alternatives to morphine, having a longer and more variable duration of analgesia (4-6 hours, even eight or more hours in some patients). A transdermal formulation of fentanyl provides analgesia for up to 72 hours.
Some morphine-like drugs are not indicated for treatment of chronic cancer pain. For example, meperidine has a toxic metabolite that can cause tremulousness, confusion, or convulsions, and is contraindicated in patients with impaired renal function and those receiving antidepressants of the monamine oxidase inhibitor class (Inturrisi and Uman 1986; Wood and Cousins 1989). Because meperidine has a very short duration of activity (2-3 hours), it is inappropriate for chronic use (WHO 1990), and should be reserved for very brief courses in otherwise healthy patients who have demonstrated an unusual reaction or allergic response to other opioids such as morphine or hydromorphone (Acute Pain Management Guideline Panel 1992). Although widely used, propoxyphene is generally not indicated for chronic cancer pain both because it is a weak opioid, offering no particular advantage compared to codeine, and because it produces dysphoric effects with chronic administration. Opioids with mixed agonist-antagonist properties such as pentazocine, nalbuphine or butorphanol are not indicated for chronic cancer pain management because they can cause psychotomimetic effects, including with chronic administration, and may induce opioid withdrawal if given to a patient receiving opioids.
Opioid Toxicity
Side effects from opioids are prevalent, most commonly constipation, nausea, and sedation. Sedation and nausea are usually short-term problems that resolve with chronic opioid administration. Patients frequently report an "allergy" to opioids, manifested by nausea and vomiting. Nausea is not an allergic manifestation of opioid use and should not be considered a contraindication to opioid use. However, many patients will need antiemetics to control nausea during initial dose titration. True allergic reactions, manifest as an anaphylactoid response, are rare (Jaffe and Martin 1990). Sedation can usually be controlled by careful dose adjustment, and tolerance will usually develop to this side effect in a short period of time. In refractory cases, small doses of stimulants such as amphetamine or methylphenidate can be used (Bruera, Brenneis, and Paterson 1989). Constipation is a problem that may not improve over time; thus, all patients receiving opioids need measures to ensure regular bowel movements. Respiratory depression is very uncommon in patients taking oral opioids chronically since tolerance to the respiratory depressant effects of opioids develops rapidly. Risk factors for respiratory depression include rapid high dose intravenous administration, rapid dose escalation of levorphanol or methadone, and new hepatic or renal dysfunction.
Tolerance, Physical Dependence, and Psychological Dependence (Addiction)
There is considerable misinformation about the effects of opioids (Jaffe 1989; Jasinski 1989) which contributes to fear of using opioid analgesics (Morgan 1986). It is important, therefore, to clarify the meaning of key concepts and terms.
Tolerance to opioids is defined as the need to increase the amount of drug to produce the same pharmacologic effect (APS 1989). The development of analgesic tolerance is a pharmacologic property of opioids and is not synonymous with addiction. Tolerance is heralded by a decrease in the duration of analgesia and is managed by increasing the dose. Since there is no ceiling dose for most opioids, the development of analgesic tolerance rarely limits opioid therapy in cancer pain management. It should be noted that many patients remain on stable doses of opioids for weeks to months with no evidence of significant tolerance (Foley 1989a). In general, increasing complaints of pain are a sign of worsening cancer and pain rather than the development of tolerance.
Physical dependence is the physiologic adaptation of the body to the presence of an opioid, and is a state in which withdrawal symptoms will develop if opioids are discontinued or an opioid antagonist is administered (APS 1989). Like tolerance, this is a pharmacologic property of opioids that is not the same as addiction and will occur in all pain patients maintained on opioids. If patients no longer need opioids because the cancer has been reduced by anti-neoplastic treatment, or because other analgesic therapies have been effective, opioids can be gradually and safely tapered over several days to avoid acute withdrawal symptoms.
As a general principle, psychological dependence, or addiction, is a condition characterized by a pattern of compulsive behavior and overwhelming involvement in acquiring a drug for non-medical purposes, e.g., for psychic effects as opposed to pain relief (APS 1989). Drug use alone is not the major factor in the development of psychological dependence. Psychological dependence (addiction) should not be confused with physical dependence (McIzack 1988; APS 1989; Portenoy 1990). Psychological dependence may or may not be accompanied by physical dependence or tolerance. Studies indicate that iatrogenic addiction is very rare, occurring in less than 0.1% of medical patients who receive opioids for pain and have no history of drug abuse (Medina and Diamond 1977; Porter and Jick 1980; Perry and Heidrich 1982). Pain patients may require frequent escalations in dose to overcome opioid tolerance and will be physically dependent on opioids without being psychologically dependent.
The under-treatment of pain may lead cancer patients to complain and to request opioids, sometimes by name. Such drug-seeking behavior mimics addictive behavior, and such patients may be incorrectly perceived as addicts by health professionals. In fact, this is an iatrogenic condition that has been termed "pseudoaddiction," and can be avoided by listening to the patient, conducting a careful pain assessment, and treating the pain (Weissman and Haddox 1989).
Adjuvants
A number of other drugs, some of which are non-opioid controlled substances, may be used to augment pain relief and symptom management. Anti-depressant or anti-convulsant medications are used to treat neuropathic pain (Speigel, Kalb, and Pasternak 1983; Swerdlow 1984). Stimulants, including dextroamphetamine and methylphenidate which are Schedule II controlled substances, may be used to overcome opioid-induced sedation and may have co-analgesic effects when used with opioids (Bruera, Brenneis, and Paterson 1989). Muscle relaxants, benzodiazepines and other sedative/hypnotics should be avoided in patients with poorly controlled pain as they generally provide sedation without analgesia. However, the benzodiazepines, which are Schedule IV controlled substances, are useful in treating co-existing anxiety conditions or sleep disorders.
Summary
There are a number of drugs, many of which are controlled substances, that are essential in the treatment of cancer related pain. These substances may be used together or in combination in order to improve overall pain and symptom management. Some patients will need only non-opioids, or opioids such as codeine or propoxyphene. However, for patients with moderate to severe pain, opioids such as morphine or hydromorphone are generally needed. The addition of adjuvant drugs to control opioid side effects, as coanalgesics or to manage other symptoms, may be necessary to provide optimal patient care. Concerns about opioid toxicity, tolerance, physical dependence, and addiction are largely unwarranted.
III. OPIOIDS AND THE LAW
Opioid analgesics, as well as the sedative and stimulant adjuvants, are controlled substances under federal and state law because of their potential to produce psychological and physical dependence. Federal and state controlled substances laws establish criminal and civil penalties for distribution and use of drugs outside of legitimate medical practice.
Federal Controlled Substances Law
The federal Controlled Substances Act (CSA) and related regulations establish a positive framework for the use of opioids in the treatment of intractable pain in the following ways:
1) The CSA recognizes that many controlled substances are necessary for the public health. The controlled substances which have been approved as safe and effective under the Federal Food, Drug and Cosmetic Act may be prescribed by physicians for legitimate medical purposes in the course of professional practice, including for indications not included in the approved labeling (U.S. v. Evers 1981; Federal Register 1983). It should be noted, however, that off-label prescribing of dronabinol, a synthetic form of THC approved by the FDA for the treatment of nausea and vomiting due to cancer chemotherapy, is an exception to this rule; the Drug Enforcement Administration (DEA) has ruled that off-label prescribing of dronabinol subjects a practitioner to possible criminal or civil action under the CSA (Federal Register 1986).
2) The CSA does not regulate legitimate medical practice with controlled substances (U.S. House of Representatives 1970). While refills are limited, medical decisions such as the amount or duration of prescribing are not regulated by the CSA.
3) The CSA is not intended to interfere with the availability of controlled substances for legitimate medical and scientific purposes (U.S. Code. Title 21. Sec. 826). The CSA requires DEA to establish production quotas for Schedule II drugs that will satisfy legitimate medical and scientific needs in the U.S. (Federal Register 1988).
4) The use of opioid analgesics to treat intractable pain is considered a legitimate medical purpose for opioids and is considered to be within professional medical practice (Code of Federal Regulations 1988). DEA has emphasized that physicians should not hesitate to prescribe controlled substances including narcotics when they are medically indicated for pain in patients with terminal illness or chronic disorders (DEA 1990a).
5) The CSA clearly distinguishes between the analgesic use of opioids and their use to maintain or detoxify a narcotic addict. Under federal law, "addict" is defined as an individual who habitually uses a narcotic drug so as to endanger public health or safety, or who has lost control over narcotic use (U.S. Code. Title 21. Sec. 802). Prescribing opioids to maintain narcotic addiction is not a legitimate medical purpose and is prohibited. However, a physician may register as a narcotic treatment program to use opioids to maintain or detoxify opioid addicts; in this event, methadone is the only opioid that has been approved for this purpose, and its use must be in accordance with applicable federal and state law and regulations. Federal controlled substances regulations allow a physician to use opioids to maintain or detoxify a person when the condition being treated is a medical or surgical condition other than addiction, such as pain (Code of Federal Regulations 1988; DEA 1990a). The regulations do not prevent physicians from using opioid analgesics to treat intractable pain in a person who has a current or past history of drug abuse.
State Controlled Substances Law
As a general rule, state laws may be, and often are, more restrictive than federal law. Also, states have the authority to license physicians and regulate medical practice. Like federal law, state laws permit the prescribing of controlled substances for legitimate medical purposes. Unlike federal law, however, most state controlled substances laws do not specifically acknowledge the medical value of controlled substances or specifically recognize that the use of opioids in treatment of intractable pain is part of legitimate medical practice (Joranson 1990a). A number of states legal definitions of "addiction" and other drug abuse-related terms denote physical dependence, thereby obscuring the critical difference between addicts and intractable pain patients (Joranson 1990a).
Ten states monitor prescribing of Schedule II controlled substances; nine require special government-issued prescription forms (DEA 1987). Two states, Oklahoma and Massachusetts, are testing an electronic monitoring system. These programs generally apply to Schedule II controlled substances, including the potent opioid analgesics. Monitoring for improper prescribing and drug abuse usually focuses on prescribing of high volumes for extended periods. Proponents of these programs assert that they are effective in reducing diversion and do not interfere with legitimate prescribing (DEA 1990b). However, it has been reported that Multiple Copy Prescription Programs have: a) reduced the prescribing of Schedule II opioids and other controlled substances by 50% or more (DEA 1987, 1990b; Weintraub et al. 1991), b) hampered the prescribing of Schedule II opioids for terminally ill patients with chronic pain (Berina et al. 1985), and c) encouraged the substitution of weaker opioids in lower schedules (Sigler et al. 1984). A recent study of oncologists showed that "excessive regulation" and "reluctance to prescribe" were reported as significantly greater barriers to cancer pain management in states with these programs (Von Roenn et al. 1991).
A few states require physicians to report patients who receive certain controlled substances for more than a few months to the state government; New York State requires these patients to be reported as addicts. In addition, some states limit the amounts of controlled substances that can be prescribed to as little as 100 dosage units at one time (Joranson 1990a).
IV. IMPEDIMENTS TO CANCER PAIN MANAGEMENT
Each situation where pain is inadequately managed is a result of a unique combination of one or more factors, or impediments, that are outside of the pain experience itself and which function to impede pain management. Impediments involve patients (Hodes 1989; Ward et al. in review), health professionals (Cleeland 1986), and the health care system and regulatory systems (Cleeland 1987). An analysis (Dahl and Joranson 1988) showed that patients lack awareness that cancer pain can be relieved, and that patients fail to report or under-report pain because of stoicism, because of fear that the disease is progressing, because of a desire to be a "good" patient, and so as not to distract the doctor from treating the disease. Patients fear becoming "addicted" and may refuse or fail to take potent pain medications. Health care professionals lack knowledge about pain and pain management, are concerned about side effects of opioids and addiction, lack confidence in the patient's report of pain, and assign a low priority to pain management. In the health care system, there is a low priority given to pain as evidenced by a lack of accountability for pain assessment and management. Opioids are unavailable in some urban pharmacies.
It has also been suggested that physicians may prescribe conservatively due to concern about scrutiny by regulatory agencies (Foley 1989b; Angarola and Wray 1989; Hill 1989; Max 1990; Portenoy 1990; McIntosh 1901; Weissman, Joranson and Hopwood 1991). To begin examining whether there is a basis for physicians to be concerned about scrutiny from regulatory agencies when prescribing opioids for cancer pain, the Pain Research Group conducted a survey of medical boards - the state agencies that license, investigate and discipline physicians. The purpose was to learn how medical board members view cancer pain, its treatment, and the legality of using opioids for cancer and non-cancer pain.
V. THE SURVEY OF MEDICAL BOARD MEMBERS
Method
A 28-item questionnaire was developed by the Pain Research Group. Several questions from previous surveys were used (Cleeland et al. 1986; Diekmann and Wassem 1991; Vortherms, Ryan and Ward in press). The survey instrument contained questions about demographics, cancer pain and its treatment, the nature and extent of addiction and diversion, the board's role in investigation, board policy concerning licensure and discipline, the legality of certain prescribing scenarios, and the existence of legal impediments to pain management. The questionnaire was pilot-tested with former members, administrators and investigators of medical boards from several states. The Wisconsin Survey Research Laboratory refined the instrument and mailed it in March, 1991 to a complete list of 627 state medical board members provided by the Federation of State Medical Boards of the U.S. A cover letter stated the subject of the survey, but did not mention issues to be examined. The letter also indicated that members would receive a report of the results, and assured respondents of confidentiality. Board administrators and executives were separately notified of the survey and provided with a copy of the questionnaire. There were two additional mailings to all non-responders. No attempt was made to ascertain the number of members on each state board, or to obtain more complete responses from individual states. The survey was not designed to ascertain the policy of individual state boards, but rather to provide a descriptive analysis of the views of a sample of all board members.
Results
Returned were 322 questionnaires (51%). Of these, 304 were evaluable
for a response rate of 49%. Respondents represented 49 states, with a mean
of 6 respondents per state. Massachusetts was the only state from which
there were no responses. The geographic distribution of respondents is
presented in Table 2.
Table 2. Frequency distribution of responses by state
|
Physician-respondents received their medical degrees between 1926 and
1987; the median year was 1961. The respondents' areas of practice or specialty
are listed in Table 3. Some physicians listed more than one specialty,
others listed none.
| Table 3. Physician-respondents' practice specialties | |
| Surgery (48)
Family Practice (38) Internal Medicine (37) General Practice (25) Psychiatry & Neurology (17) Obstetrics & Gynecology (12) Radiology (9) Pediatrics (8) Ophthalmology (7) Otolaryngology (7) Pathology (7) |
Addictive Medicine (4)
Anesthesiology (4) Dermatology (4) Neurological Surgery (4) Urological (3) Emergency Medicine (1) Physical Medicine (2) Administrative Medicine (l) Nuclear Medicine (1) Preventive Medicine (1) Other (8) |
Board members were asked several questions about cancer pain and its treatment. Eighty percent of the respondents correctly believed that 70% or more of cancer patients will suffer from pain at some point during their illness. Fifty-eight percent of the respondents correctly believed that 80% or more of cancer-related pain can be relieved by treatment with anti cancer drugs, surgery, radiation, and analgesics.
Respondents were about equally divided in their opinions about how well the pain of cancer is treated. Approximately one-half (49%) of the respondents felt that most cancer patients are under-medicated. Forty-three percent believed that most cancer patients receive adequate pain treatment while 5% believed that most are overmedicated.
The physician members were asked to rank from a list of 12 opioid analgesics
those that they would recommend for use in the management of prolonged
moderate to severe cancer pain. They were also asked to indicate those
opioid analgesics that they would not recommend be used. The results are
presented in Table 4. For prolonged moderate to severe cancer pain, a small
percentage of the physician-respondents recommended use of the preferred
opioids like morphine, hydromorphone and levorphanol. Codeine-combination
products were recommended by many respondents but are generally considered
too weak for prolonged moderate to severe pain. Meperidine, which is inappropriate
because of its toxicity, was recommended about as often as it was recommended
against. Opioid analgesics that are useful were recommended against by
many respondents, including levorphanol, methadone, and hydromorphone.
Nearly half of the respondents recommended against pentazocine, which is
not preferred for prolonged treatment of moderate to severe pain.
| Table 4: Physician board member rankings of analgesics for treatment of prolonged moderate to severe cancer pain | |||
| Ranked as 1, 2, or 3 | Would not recommend | ||
| 1. aspirin/acetaminophen and codeine | 47% | 1. levorphanol | 50% |
| 2. aspirin/acetaminophen and oxycodone | 35% | 2. methadone | 45% |
| 3. morphine | 25% | 3. pentazocine | 44% |
| 4. aspirin/acetaminophen | 21% | 4. single entity codeine | 42% |
| 5. meperidine | 18% | 5. aspirin/acetaminophen | 37% |
| 6. propoxyphene | 17% | 6. Brompton's cocktail | 34% |
| 7. hydromorphone | 13% | 7. propoxyphene | 33% |
| 8. Brompton's cocktail | 9% | 8. hydromorphone | 24% |
| 9. single entity codeine | 9% | 9. meperidine | 17% |
| 10. methadone | 7% | 10. aspirin/acetaminophen and oxycodone | 9% |
| 11. pentazocine | 6% | 11. aspirin/acetaminophen and codeine | 8% |
| 12. levorphanol | 2% | 12. morphine | 6% |
Addiction, Abuse and Diversion
All board members were asked to indicate the approximate incidence of psychological dependence (defined as compulsive use for non-medical purposes) that results from the opioid treatment of pain. Nearly 40% indicated they did not know; 16% thought the incidence was one in 10; 23% chose one in 100; 12% chose one in 1000; 9% chose less than one in 1000.
Respondents were asked the meaning of "addiction" and given several common definitions from which to select: physical dependence, psychological dependence, tolerance, other, and don't know. Respondents were allowed to choose more than one answer. Eighty-five percent of board members said that "addiction" means physical dependence, 71% psychological dependence, 41% tolerance; 21% indicated physical dependence alone, 10% chose psychological dependence alone, and 1% selected tolerance alone.
Over half of the board members said that the diversion and abuse of prescription opioid analgesics was a problem in their state; 10% felt it was a serious problem; 30% believed it was a moderate problem; 22% believed it was a minor problem.
Board Policies
Several questions were asked in order to gain a preliminary view of whether state medical boards may have policies in areas related to the prescribing of opioids for pain. Twenty-eight percent of the respondents (from 31 states) said that their board had a written policy or guidelines for appropriate prescribing of opioids. Twenty-two percent of the respondents (from 32 states) indicated that their board's licensure process required an applicant to have knowledge about the treatment of pain. Five percent of board members (from 11 states) were aware of a physician in their state who had been investigated or disciplined by the board for failure to treat pain. A follow-up request for information about such policies has been sent to all medical boards.
Legal Impediments
Medical board members were asked if they thought any state laws or regulations impeded the medical use of opioids to treat pain. Twelve percent of respondents (from 26 states) answered affirmatively and supplied the name of the law or regulation. Most of these responses referred generally to the state medical practice act or regulations; a few mentioned controlled substances laws. Several board members mentioned specific concerns, including the triplicate prescription requirement (New York and Illinois), the prohibition against "clearly excessive prescribing" (California), and a concern about treating chronic non-malignant pain (Oregon). A few board members mentioned physicians' concern about regulatory agencies, the "general prejudice by investigators of any long-term prescribing," and the inability to refill Schedule II prescriptions.
Perceived Legality of Prescribing Opioids for Chronic Pain
Board members were asked to give their opinion as a member of the state medical board about the legality and medical acceptability of prescribing opioids for more than several months in four patient scenarios involving cancer and nonmalignant pain, with and without a history of opioid drug abuse. There were four possible levels of legality for each scenario: 1) lawful and generally acceptable medical practice; 2) lawful, but generally not acceptable medical practice which should be discouraged; 3) probably a violation of my state's medical laws and regulations which should be investigated; and 4) probably a violation of federal or state controlled substances laws which should be investigated. Respondents were allowed to give more than one response in case they thought that more than one level of illegality was applicable (see Table 5). It should be noted that in general, proceedings for violations of medical practice laws usually involve disciplinary action, including revocation of license, while state or federal controlled substances law proceedings often involve criminal prosecutions, forfeitures, revocation of controlled substances registration, or a combination, and may include substantial fines or civil penalties.
Column 1 in Table 5 represents the highest level of medical board member
confidence in the prescribing practice, i.e., the practice is perceived as both legal and generally accepted medical
practice. The other columns represent declining confidence in the practice;
column two represents a "lawful but discourage" attitude, while columns
three and four indicate that the practice is illegal under either medical
practice or controlled substances law, or both, and should be investigated.
The fact that 80% of the medical board members said that their medical
board was the agency most likely to investigate improper prescribing of
controlled substances in their state underscores the significance of these
data.
| Table 5. Perceived legality of prescribing opioids for an extended period | |||||
| Level of perceived legality | |||||
| Patient History | 1. Lawful and generally acceptable medical practice | 2. Lawful, but generally not acceptable medical practice; should be discouraged | 3. Probable violation of medical practice laws and regulations; should be investigated | 4. Probable violation of federal/state controlled substances laws; should be investigated | 5. Don't know |
| A. Cancer pain only | 75% | 14% | 5% | 5% | 7% |
| B. Cancer pain with history of opioid abuse | 46% | 22% | 14% | 12% | 16% |
| C. Chronic non-malignant pain only | 12% | 47% | 32% | 27% | 7% |
| D. Chronic non-malignant pain with history of opioid abuse | 1% | 25% | 58% | 50% | 6% |
Scenario A: Cancer pain only
Three-fourths of the respondents demonstrated a high level of confidence in the legality and medical acceptability of prescribing opioids for more than several months for cancer patients with pain. At the same time, 14% would discourage this practice even though they perceive the practice to be legal; 5% would investigate the practice as a violation of medical or controlled substances law.
Scenario B: Cancer pain with a history of opioid abuse
If the cancer patient with chronic pain has a history of opioid abuse, less than one-half of the respondents were confident in prescribing opioids. Twenty-two percent would discourage the practice, 14% would investigate the practice as a probable violation of medical practice law. Overall, respondents chose "don't know" more often (16%) for this patient scenario than for the other scenarios.
Scenario C: Nonmalignant pain
If the patient's chronic pain is of non-malignant origin, only 12% of respondents were confident that prescribing opioids for an extended period for such an individual is legal and acceptable medical practice. Nearly half (47%) perceive the practice to be legal, but would discourage it. A third perceived the practice to be probably illegal and would investigate it.
Scenario D: Non-malignant pain with a history of opioid abuse
Only 1% of the medical board members viewed the prescribing of opioids for more than several months to a patient with chronic non-malignant pain and a history of opioid abuse as legal and acceptable medical practice. One-fourth of the board members thought the practice was legal but would discourage it; one-half of the medical board members believed the practice to be in probable violation of controlled substances law and should be investigated.
Communication with Practitioners: Need for More Information
At the end of the questionnaire, all respondents were asked an open-ended question about what they would like to communicate to physicians who prescribe opioids to patients with pain. Ninety percent of the board members responded by writing a response. Their responses consisted of the following themes: 1) importance of knowing medications and how to treat pain, including monitoring use and starting with the weakest medication (37%); 2) importance of diagnosis - that is, the accuracy of the diagnosis, consulting with other physicians for a second opinion, having a "good medical workup," and the use of monitoring and good judgment (18%); and 3) the importance of liberal prescribing for terminally ill patients, including that the potential for addiction should not be a primary concern when treating such patients (12%).
A second open-ended question asked what additional information would be useful to them in making decisions about any of the areas mentioned in the survey. Thirty-six percent of board members responded to this question, wanting to have more information about the causes, measurement and treatment of pain; the use of medications; laws, rules and regulations; and recommended prescribing policies and protocols.
Discussion
These data represent the opinions of approximately half of the board members who interpret and enforce state medical practice laws and regulations in the U.S. No attempt was made to determine if the response rate in any state was great enough to be representative of a particular board. The survey results do not necessarily represent the actual legal status of certain practices, or the policy of state medical boards, individually or collectively. Such determinations should be made by consulting the applicable law or board.
Cancer Pain and Its Treatment
The results of this survey indicate that most, but not all, medical board members recognized the extent to which people with cancer are likely to suffer pain. Almost half of the respondents underestimated the degree of relief that can be attained with proper treatment, and the extent to which cancer pain is under-medicated. Significant numbers of physician members underestimated the need to use potent opioids, such as morphine, for moderate to severe cancer pain. Many would not recommend opioids that are recognized as useful, and some would recommend drugs that are not indicated for chronic cancer pain management. Most board members either did not know or overestimated the incidence of psychological dependence when opioids are used to treat pain. In general, the survey data indicate that while many state medical board members recognize that cancer may be painful, they could benefit from the knowledge that opioids can be used to relieve cancer pain without significant risk of addiction.
Addressing Problems of Diversion
Forty percent of the medical board members believed there was a moderate or serious problem of diversion of prescription opioids in their state. States should evaluate the nature and extent of diversion because of the potential public health consequences associated with drug abuse. Both the nature and the extent of opioid diversion can and should be assessed using data that are currently available (Treffert and Joranson 1981; AMA 1990; Virginia Department of Health Professions 1991). Depending upon the type of problems found (e.g., "script doctors," forgers, pharmacy theft or "doctor shoppers"), interventions should be designed to address the individual sources, or vectors, that are responsible for diversion. Interagency cooperation is essential in order to make use of existing sources or information and to pool investigative resources, and should also involve the development of practitioner education programs (Treffert and Joranson 1981; Chi 1983; Wisconsin Controlled Substances Board 1986, 1988; Virginia Department of Health Professions 1991). Great care should be taken to avoid interventions that interfere with legitimate medical practice (Joranson and Dahl 1989; Joranson in press). At least one state has acknowledged the possibility that diversion control efforts may have hampered medical practice with controlled substances and has taken steps to correct the situation (Dahl and Joranson 1990). Evaluation of diversion indicators should be a continuous process to determine the extent to which interventions have been effective. The DEA has reported significant declines in indicators of diversion of prescription controlled substances (Haislip 1989).
"Addiction"
Most board members' definitions of "addiction" included both physical and psychological dependence, and to a lesser extent, tolerance. Confusion about the meaning of addiction in relation to physical dependence and tolerance can interfere in the evaluation of the potential for addiction in the treatment of patients with chronic pain (Portenoy 1990; Ferrell, McCaffery, and Rhiner 1992). The public fears the use of opioids, even for the treatment of cancer pain (Levin, Cleeland, and Dar 1985). Cancer patients fear becoming "addicted," and avoid opioid analgesics (Hodes 1989). The consequence of confusing physical dependence with addiction in a pain patient may result in mistaken admissions to methadone maintenance programs (Joranson 1990a) and may result in expensive lawsuits against caregivers for failure to treat cancer pain (Angarola 1991).
A common view of addiction that is often heard in conversations about cancer pain and opioids is "so what if they get addicted, they are going to die anyway." This putative humane approach confuses physical dependence with addiction and then excuses it on the grounds of terminal illness, leaving the person with cancer stigmatized despite the rare occurrence of addiction. It would be preferable to revise our understanding of addiction and adjust our level of concern in relation to the very low likelihood of its occurrence when opioids are used to manage cancer pain.
Confusing addiction with physical dependence and tolerance in the arena of medical discipline may also lead to legitimate prescribing practices being perceived as unacceptable or even illegal.
The Medical Acceptability and Legality of Prescribing Opioids for Extended Periods
Board members' confidence in the acceptability of prescribing opioids for more than several months started at only 75%, even when the source of chronic pain was cancer, and declined to 1% when the source of pain was non-malignant and there was a history of opioid abuse. This decline was accompanied by an increase in the perception that the practices should either be discouraged or investigated as a probable violation of law. What is the legal and medical status of these prescribing scenarios?
From a legal perspective, it is important to recognize that the presenting
problem in each scenario in Table 5 is pain, not addiction. The treatment
of pain, including drug therapy, is considered to be within the scope of
licensed medical practice (Federation of State Medical Boards of the United
States 1988). As discussed previously, the use of opioids to treat pain,
including intractable pain, is considered a legitimate medical practice
under federal controlled substances laws and regulations. This is also
true for the use of opioids to treat pain in a person who is an addict;
this is a clinical practice that is being carefully explored (Hoffman et
al. 1991).
Broadly, the medical decision to use opioids for a particular patient
with chronic pain is based on an assessment of the relative benefits and
risks to the patient. There is a clear medical consensus that the extended
use of opioids to manage cancer pain is an acceptable medical practice,
even an essential one (WHO 1986, 1990). Practice principles and guidelines
have been available for at least 10 years (see box). The Agency for Health
Care Policy and Research (1992) is preparing a clinical practice guideline
for cancer pain that is expected to be available early in 1993. A number
of state, national, and international health authorities are developing
medical education programs to improve the use of opioids in the management
of cancer pain in the U.S. and throughout the world (WHO 1986, 1990, 1991,
1992; Dahl and Joranson in press; Steele 1990). Furthermore, state, federal,
and international law enforcement and drug control organizations have recognized
the extended use of opioids in the treatment of chronic cancer pain (National
Association of State Controlled Substances Authorities 1989; DEA 1990a;
INCB 1989).
Under federal law, the legality of using opioids for an extended period does not change if the patient's diagnosis is chronic non-malignant pain. At the state level the authors are unaware of outright prohibitions of this practice. However, some medical boards have responded in different ways to the use of opioids in chronic non-malignant pain.
At least one board (Oregon) has focused investigative efforts in this direction (Portenoy 1990; Kofoed et al. 1989), and one board (Washington) has indicated it does not recognize prescribing of controlled drugs as appropriate therapy for chronic pain, although the board clarified that this policy was not intended to interfere with clinical judgment in the care of patients with chronic pain (Washington State Medical Disciplinary Board 1989). The Texas Board of Medical Examiners issued a statement clarifying that the prohibition on prescribing narcotics to an habitual user was intended to apply only to "habituated patients for whom the repeated use of narcotics or other drugs is not otherwise medically indicated" (Texas State Board of Medical Examiners 1988). Subsequently, Texas and then California adopted Intractable Pain Treatment Acts that define intractable pain without regard to whether the source of pain is malignant, and which recognize the physician's ability to use opioids to treat intractable pain. As previously noted, the Massachusetts board has endorsed guidelines for physicians to use when managing chronic nonmalignant pain with opioids.
Guidelines for the use of opioids in the management of chronic non-malignant
pain are not as well-developed as in cancer pain. The long-term use of
opioid analgesics for patients with non-malignant pain has been criticized
for many years in the U.S. because of concerns about both iatrogenic addiction
and interference of drugs with the recovery of the patient's functioning
(Portenoy 1990). More recently, new knowledge about pain and pharmacology
and the extensive experience in managing cancer patients without significant
problems with tolerance and addiction has stimulated a reevaluation of
the role of opioids in chronic nonmalignant pain within the medical and
scientific community (Portenoy and Foley 1986; Turk and Brody 1991; Dubner
1991; Melzack 1988). Portenoy (1990) has reviewed the literature and has
suggested that "there probably is a selected subpopulation of patients
with chronic non-malignant pain who may obtain sustained partial analgesia
without the development of toxicity or the psychologic and behavioral characteristics
of addiction." It should be recognized that chronic pain, regardless of
its source, is debilitating; unrelieved chronic nonmalignant pain may even
lead to suicide (Fishbain et al. 1991). Clearly, there is a need to establish
the efficacy and safety of opioids in chronic non-malignant pain conditions;
clinical investigation and research are proceeding. The Agency for Health
Care Policy and Research (1992) has plans to develop clinical practice
guidelines for the management of chronic non-malignant pain including low
back pain problems. Dubner (1991) recently called for "more science, not
more rhetoric, regarding opioids and neuropathic pain," recognizing that
many patients with chronic non-malignant pain are not obtaining pain relief.
Dubner (1991) recommended that "(c)areful administration of opioids in
the manner suggested by Portenoy (1990) should continue while well-controlled
clinical trials are undertaken to establish opioid analgesic efficacy."
Portenoy's proposed guidelines, developed from a review of existing literature
and clinical experience, appear in Table 6. The Commonwealth of Massachusetts
Board of Registration in Medicine has also endorsed guidelines for prescribing
opioid analgesics for patients with chronic non-malignant pain (Commonwealth
of Massachusetts Board of Registration in Medicine, 1989).
|
Proposed Guidelines in the Management of Opioid Maintenance Therapy for Non-Malignant Pain
|
Pain and a History of Drug Abuse
Based on limited data, it appears that cancer patients with a history of drug abuse are at high risk for inadequate pain management due to prevalent concerns about addiction (Macaluso, Weinberg, and Foley, 1988). This patient population may grow as substance abusers age and develop cancers. Further, many AIDS patients, some of whom have a history of drug abuse, are developing a variety of cancers and other painful conditions. Professional concern about the pain treatment needs of this population is relatively recent and growing, and the development of principles and guidelines for the use of opioids in such patients has begun (Hoffman et al. 1991). The use of opioids in chronic non-malignant pain patients with a history of drug abuse is even less well developed. It will be important to carefully study pain control in this latter population and to develop practice guidelines that help clinicians decide which patients may benefit from the use of a variety of pain management techniques, including the use of opioid analgesics.
Although federal law and regulations allow physicians to use opioids as analgesics to treat pain regardless of the history of the patient, some state medical laws and regulations may indeed restrict physicians from using (opioids to manage pain in this patient population. The Federation of State Medical Boards of the U.S. (1988) has recommended that state medical practice acts include as grounds for disciplinary action against a physician "except as otherwise permitted by law, prescribing, selling, administering, distributing, or giving to an habitué or addict or any person previously drug dependent any drug legally classified as a controlled substance or recognized as an addictive or dangerous drug" (Federation of State Medical Boards of the United States 1988). (The exception in the foregoing appears to refer to physicians who are registered to maintain or detoxify addicts with methadone). The extent to which states have adopted this recommendation is unknown; it is important that state policy not prohibit the option of using opioids to manage pain in patients with a history of drug abuse.
It is recognized that medical boards confront prescribing practices that are outmoded, injudicious, sloppy, or dishonest, that these are the exception rather than the rule, and that they should be identified and addressed. It is of utmost importance to distinguish between improper prescribing and prescribing that is for bona fide pain management. Reliance on the amount or duration of opioid prescribing will impair the ability to make this crucial differentiation. Instead, standard medical disciplinary criteria should be used, such as benefit or harm to the patient, lack of caution, inadequate knowledge, incompetence or negligence. Guidelines that are based on research and clinical experience can benefit physicians and boards alike in ascertaining a reasonable standard of care. In those areas of practice that await guidelines or standards of care, the determination of appropriateness in individual cases should continue to rely on the use of standard medical disciplinary criteria, and on testimony from recognized experts. The areas of practice where there is not yet a consensus should not be regarded as illegal on their face, but should remain open to clinical practice and research so that patients may benefit and new medical knowledge and standards of care can be developed.
Conclusions
Through the efforts of many state and national health care organizations including the National Cancer Institute and the Agency for Health Care Policy and Research, new programs are emerging to address the unnecessary suffering of people with cancer and pain (Dahl and Joranson, in press). Among these are the state cancer pain initiatives, which began with a World Health Organization demonstration project in Wisconsin in 1986, and have spread to more than 25 other states (Dahl, Joranson and Weissman 1989; WHO 1992). These actions include informing the public and patients that cancer pain can be relieved, and educating health care professionals about the proper management of cancer pain. Hopefully, the result will be increasing numbers of cancer patients who will expect pain relief, and increasing numbers of physicians, nurses, pharmacists, and other health care professionals who will practice according to generally accepted principles of analgesic therapy.
Burgeoning cancer pain relief efforts in the U.S. should also include liaison with state medical boards in order to inform them of advances in this area of medical practice. Indeed, board members appear to be interested in the cancer pain problem, as evidenced by the overall high response rate to the survey, their willingness to take time to write advice to practitioners, and their expressed interest in obtaining additional information. The Pain Research Group presented an educational program at the 1991 annual meeting of the Federation of State Medical Boards of the U.S., is reporting these survey results directly to board members, has provided information about state cancer pain initiatives to every board, and is reviewing state laws and regulations for potential impediments.
Future Directions
The survey showed that board members' knowledge about the use of opioids and other controlled substances to manage pain, in particular cancer pain, needs to be improved. This is not surprising since this information is not yet well-assimilated into medical education. One example of what can be done is a symposium that was sponsored in 1991 by the Oregon Foundation for Medical Excellence in cooperation with several state medical boards and the American Pain Society. The symposium brought national pain experts together with board members for a day-long research-based discussion on the rational use of controlled substances in the management of pain. The findings of the AHCPR could serve as a focus for future meetings.
Suggested Approaches
The survey also indicated that board members to varying degrees doubt the acceptability and even the legality of prescribing opioid analgesics for intractable pain, particularly if the patient does not have cancer or has a history of drug abuse. It would be useful for boards to review state law and policy to assure that they do not interfere with the appropriate medical use of opioids and other controlled substances in the management of cancer and non-cancer pain (Joranson, in press). Medical boards may want to consider adoption of the revised Uniform Controlled Substances Act which offers a model interagency diversion control program and clearly recognizes the medical uses of controlled substances, including the use of opioids in the treatment of intractable pain (National Conference of Commissioners on Uniform State Laws 1990; Joranson, 1990b).
Following such a review, it would be useful for boards to communicate with licensees to endorse the rational use of opioids and other controlled substances in the management of cancer and non-cancer pain. This would also be an opportunity to explain the criteria that the board uses to determine unprofessional or substandard conduct, and to clarify that the number of pills or the duration of prescribing alone do not constitute inappropriate conduct. Such an action by boards would provide welcome leadership to improve pain management and could also help to alleviate concerns physicians have about regulatory scrutiny (Hill 1989; Weissman, Joranson and Hopwood 1991). Ultimately, if medical boards have reasonable policies which are understood by state physicians, it may be possible to reach the ideal circumstance where physicians will not view as a threat inquiries from the board about their prescribing. It is especially important that the approaches suggested here be considered by any state agency other than the medical board that is involved in the regulation of medical practice with controlled substances.
In conclusion, it should be recognized that in part, fear of uncontrolled pain due to cancer and other debilitating conditions propels the current interest in euthanasia, physician assisted suicide and suicide (Foley, 1991; Connolly, 1989). The World Health Organization has recommended that government agencies throughout the world attend to cancer pain relief and palliative care before considering laws allowing euthanasia (WHO, 1990). Furthermore, the International Narcotics Control Board (INCB), the United Nations body that administers international drug control treaties, has expressed concern that the medical need for opioids is not being fully met, and that this is due in part to fears of drug abuse and some laws, regulations, and interpretations that unduly impede the medical use and availability of opioids (INCB, 1989). The INCB has urged governments, including the United States, to ensure that their laws do not impede the appropriate medical use of opioid analgesics, and has encouraged health professionals to promote rational use of opioids, while guarding against their abuse. State medical boards can play a critically important role in responding to this challenge.
| Acknowledgments The authors wish to thank the following individuals for their thoughtful review of the manuscript: Sandra Ward, PhD, RN; Robert T. Angarola, JD; June L. Dahl, PhD; William L. Marcus, JD; Russell K. Portenoy, MD. |
Acute Pain Management Guideline Panel. 1992. Acute Pain Management: Operative or Medical Procedures and Trauma. Clinical Practice Guideline. AHCPR Pub. No. 92-0032. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services.
Agency for Health Care Policy and Research. March 1992. Fact sheet.
American Cancer Society. 1992. Cancer Facts & Figures - 1992. American Cancer Society, Inc., Atlanta, GA.
American Medical Association. 1990. Balancing the Response to Prescription Drug Abuse: Report of a National Symposium on Medicine and Public Safety. American Medical Association, Department of Substance Abuse, B.B. Wilford Editor.
American Pain Society. 1992. Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer Pain. A Concise Guide to Medical Practice. 3rd Edition.
Angarola, R.T. 1991. Inappropriate pain management results in high jury award. Journal of Pain and Symptom Management 6(7):407.
Angarola, R.T., and S.D. Wray. 1989. "Legal impediments to cancer pain treatment." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill Jr., and W.S. Fields, 213-231. New York: Raven Press, Ltd.
Berina, L.F., B.G. Guernsey; J.A. Hokanson; W.H. Doutré, and L.E. Fuller. 1985. Physician perception of a triplicate prescription law. American Journal of Hospital Pharmacy, 42:857-859.
Bonica, J.J. 1985. "Treatment of cancer pain: Current status and future needs." In: Advances in Pain Research and Therapy, Volume 9, eds. H.L. Fields; R. Dubner, and F. Cerveo, 589-616. New York: Raven Press, Ltd.
Breitbart, W. 1990. "Cancer pain and suicide." In: Advances in Pain Research and Therapy, Volume 16, eds. KM. Foley, et al., 399-412. New York: Raven Press, Ltd.
Bruera, E.; C. Brenneis, and A.H. Paterson. 1989. Use of methylphenidate as an adjuvant to narcotic analgesics in patients with advanced cancer. Journal of Pain and Symptom Management 4:3-6.
Chi, KS. 1983. Prescription drug abuse control: The Wisconsin approach. Innovations. April. The Council on State Governments, Lexington, KY.
Cleeland, C.S. 1984. The impact of pain on the patient with cancer. Cancer 54 (11: suppl): 2635-2641.
_____. 1986. Factors influencing physician management of cancer pain. Cancer 58(3):796-800.
_____. 1987. Barriers to the management of pain. Oncology 1(suppl): 19-26.
Cleeland, C.S.; L.M. Cleeland; R. Dar, and L. Rinehardt. 1986. Factors influencing physician management of cancer pain. Cancer 58(3): 796-800.
Code of Federal Regulations. 1988. Part 21. Sec. 1306.07.
Commonwealth of Massachusetts Board of Registration in Medicine. 1989. Prescribing Practices Policy and Guidelines.
Connolly, M.E. 1989. Alternative to euthanasia: Pain management. Issues in Law and Medicine 4(4):497-507.
Coyle, N. 1989. Continuity of care for the cancer patient with chronic pain. Cancer 63:2289-2293.
Dahl, J., and D.E. Joranson. 1988. A report on the Wisconsin Cancer Pain Initiative. Journal of Pain and Symptom Management 3 (suppl): S1-S20.
_____. 1990. The Wisconsin Cancer Pain Initiative. Advances in Pain Research and Therapy 16:499-503.
_____. (in press). Cancer pain: The US responds. Palliative Medicine.
Dahl, J., D.E. Joranson, and D.E. Weissman. 1989. The Wisconsin Cancer Pain Initiative: A progress report. The American Journal of Hospice Care, November/December.
Daut, R.L., and C.S. Cleeland. 1982. The prevalence and severity of pain in cancer. Cancer 50:1913-1918.
Diekmann, J., and R. Wassem. 1991. Nursing students' perceptions of cancer pain control. Cancer Nursing 14:314-320.
Donovan, M.; P. Dillon, and L. McGuire. 1987. Incidence and characteristics of pain in a sample of medical-surgical inpatients. Pain 30:69-87.
Drug Enforcement Administration. 1987. Multiple Copy Prescription Programs Resource Guide. U.S. Department of Justice, Drug Enforcement Administration, Office of Diversion Control.
Drug Enforcement Administration. 1990a. Physician's Manual: An informational outline of the Controlled Substances Act of 1970. U.S. Department of Justice, Drug Enforcement Administration.
Drug Enforcement Administration. 1990b. Multiple Copy Prescription Programs Resource Guide. U.S. Department of Justice, Drug Enforcement Administration, Office of Diversion Control.
Dubner, R. 1991. A call for more science, not more rhetoric, regarding opioids and neuropathic pain. Pain 47:1-2.
Federal Register. Vol. 48, 2673 (1983).
Federal Register. Vol. 51, 17476-17478 (1986).
Federal Register. Vol. 53, 50591-50597 (1988).
Federation of State Medical Boards of the United States. 1988. A Guide to the Essentials of a Modern Medical Practice Act, Fifth Edition.
Federation of State Medical Boards of the United States, Inc, Houston, TX.
Ferrell, B.R.; C. Wisdom, and C. Wenzl. 1989. Quality of life as an outcome variable in the management of cancer pain. Cancer 63:2321-2327.
Ferrell, B.R.; M. McCaffery, and M. Rhiner. 1992. Pain and addiction: An urgent need for change in nursing education. Journal of Pain and Symptom Management 7(2):117-124.
Fishbain, D.A.; M. Goldberg; R.S. Rosomoff, and H. Rosomoff. 1991. Case report: Completed suicide in chronic pain. The Clinical Journal of Pain 7:29-36.
Foley, K.M. 1985. Treatment of cancer pain. New England Journal of Medicine 313(2):84-95.
____. 1989a. Controversies in cancer pain: Medical perspectives. Cancer 63:2258-2265.
____. 1989b. "The 'decriminalization' of cancer pain." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill Jr., and W.S. Fields, 5-18. New York: Raven Press, Ltd.
____. 1991. The relationship of pain and symptom management to patient requests for physician-assisted suicide. Journal of Pain and Symptom Management 6(5):289-297.
Greenwald, H.P.; J.J. Bonica, and M. Bergner. 1987. The prevalence of pain in four cancers. Cancer 60:2563-2569.
Haislip, G.R. 1989. "Impact of drug abuse on legitimate drug use." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill and W.S. Fields, 205-211. New York: Raven Press, Ltd.
Hatfield, A.K; C.S. Cleeland; R. Gonin; K.S. Wagler, and K.J. Pandya. 1991. Results of an outpatient pain survey in outpatient cancer centers: An ECOG pilot study. Presented at ASCO meeting in Houston, TX, May 19-21.
Hill, C.S. 1989. The negative effect of regulatory agencies on adequate pain control. Primary Care and Cancer, November 47-53.
Hodes, R.L. 1989. "Cancer patient's needs and concerns when using narcotic analgesics." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill and W.S. Fields, 91-99. New York: Raven Press.
Hoffman, M.; A. Provatas; A. Lyver, and R. Kanner. 1991. Pain management in the opioid-addicted patient with cancer. Cancer 68:1121-1122.
Inturrisi, C.E., and J.G. Uman. 1986. "Meperidine biotransformation and central nervous system toxicity in animals and humans." In: Advances in the Management of Clinical Pain, eds. K.M. Foley, and C.E. Inturrisi, 143-153. New York: Raven Press, Ltd.
International Narcotics Control Board. 1989. Demand for and supply of opiates for medical and scientific needs. In: Report of the International Narcotics Control Board for 1989. United Nations.
Jaffe, J.H. 1989. "Misinformation: Euphoria and addiction." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill, and W.S. Fields, 163-174. New York: Raven Press, Ltd.
Jaffe, J.H., and W.R. Martin. 1990. "Opioid analgesics and antagonists." In: The Pharmacological Basis of Therapeutics, 8th Edition, eds. A.G. Gilman et al., 491 - 531. New York: Pergamon Press, Inc.
Jasinski, D.R. 1989. "Pharmacological misinformation that prevents optimum pain control with narcotic analgesics." In: Advances in Pain Research and Therapy, Volume 11, eds. C.S. Hill, and W.S. Fields, 139, 144. New York: Raven Press, Ltd.
Joranson, D.E. 1990a. Federal and state regulation of opioids. Journal of Pain and Symptom Management 5:S12-S23.
_____. 1990b. A new drug law for the states: An opportunity to affirm the role of opioids in cancer pain relief. Journal of Pain and Symptom Management 5(5)333-336.
_____. (in press). "Guiding principles of international, federal and state laws pertaining to medical use and diversion of controlled substances." In: National Institute on Drug Abuse Technical Series "Evaluation of the Impact of Prescription Drug Diversion Control Systems on Medical Practice and Patient Care: Possible Implications for Future Research."
Joranson, D.E., and J.L. Dahl. 1989. Achieving balance in drug policy: The Wisconsin model. Advances in Pain Research and Therapy 2:197-203.
Kofoed, L.; J.D. B1oom; M.H. Williams; C. Rhyne, and M. Resnick. 1989. Physicians investigated for inappropriate prescribing by Oregon Board of Medical Examiners. Western Journal of Medicine 150: 597-601.
Levin, D., C.S. Cleeland, and R. Dar. 1985. Public attitudes toward cancer pain. Cancer 56(9): 2337-2339.
Macaluso, C.; D. Weinberg, and K.M. Foley. 1988. Opioid abuse and misuse in a cancer pain population. (Abstract) Journal of Pain and Symptom Management 3:S54.
Max, M.B. 1990. Improving outcomes of analgesic treatment: Is education enough? Annals of Internal Medicine 113:885-889.
_____. 1991. "Neuropathic pain syndromes." In: Advances in Pain Research and Therapy, Volume 18, eds. M.B. Max; R.K Portenoy, and E.M. Laska, 193-219. New York: Raven Press, Ltd.
Max, M.B.; S.C. Schafer.; M. Culane; R. Dubner, and R.H. Gracely. 1988. Association of pain relief with drug side effects in post therapeutic neuralgia: A single-dose study of clonidine, codeine, ibuprofen and placebo. Clinical Pharmacology and Therapeutics" 43:363-371.
McIntosh, H. 1991. Regulatory barriers take some blame for pain undertreatment.. Journal of the National Cancer Institute 83(17)12021204.
Medina, J.L., and S. Diamond. 1977. Drug dependency in patients with chronic headache. Headache 17:12-14.
Melzack, R. 1988. The tragedy of needless pain: A call for social action. Scientific American 262(2):27-33.
Morgan, J.P. 1986. American opiophobia: Customary underutilization of opioid analgesics. Advances in Alcohol and Substance Abuse 5:163-173.
National Association of State Controlled Substances Authorities. Resolution 89 1. November 4, 1989.
National Conference of Commissioners on Uniform State Laws. 1990. Uniform Controlled Substances Act.Milwaukee, Wisconsin.
Perry, S., and G. Heidrich. 1982. Management of pain during debridement: A survey of U.S. burn units. Pain 13:267-280.
Peteet, J.; V. Tay; G. Cohen, and J. Maclntyre. 1986. Pain characteristics and treatment in an outpatient cancer population. Cancer 57(6):1259-1265.
Portenoy, R.K. 1989. Cancer pain: Epidemiology and syndromes. Cancer 63:2298-2307.
_____. 1990. Chronic opioid therapy in nonmalignant pain. Journal of Pain and Symptom Management 5(1):S46-S62.
Portenoy, R.K, and KM. Foley. 1986. Chronic use of opioid analgesics in nonmalignant pain: Report of 38 cases. Pain 25:171-186.
Portenoy, R.K.; K.M. Foley, and C.E. Inturrisi. 1990. The nature of opioid responsiveness and its implications for neuropathic pain: New hypotheses derived from studies of opioid infusions. Pain 43:273-288.
Porter, J., and H. Jick. 1980. Addiction rare in patients treated with narcotics. New England Journal of Medicine 302:123.
Sigler, K.A; B.G. Guernsey; N.B. Ingrim; A.S. Buesing; J.A. Hokanson; E. Galvan, and W.H. Doutre. 1984. Effect of a triplicate prescription law on prescribing of Schedule II drugs. American Journal of Hospital Pharmacy 41:108- 111.
Speigel, K.; R. Kalb, and G.E. Pasternak. 1983. Analgesic activity of tricyclic antidepressants. Annals of Neurology 13:464-465.
Steele, J. 1990. Cancer pain workshop develops recommendations. Journal of Pain and Symptom Management 82(20): 1611-1612.
Swerdlow, M. 1984. Anticonvulsant drugs and chronic pain. Clinical Neuropharmacology 7:51-82.
Takeda, P. 1987. Results of field-testing of the WHO draft interim guidelines on relief of cancer pain in Japanese cancer patients. In: 1986 Symposium on Pain Control, International Congress and Symposium Series, No. 123, ed. D. Doyle, 109-117. London: Royal Society of Medicine.
Texas State Board of Medical Examiners. 1988. Newsletter. 10:2, Fall-Winter.
Treffert, D.A., and D.E. Joranson. 1981. Restricting amphetamines: Wisconsin's success story. Journal of the American Medical Association 245(13):1336.
Turk, D.C., and M.C. Brody. 199 1. Chronic opioid therapy for persistent noncancer pain: Panacea or oxymoron? American Pain Society Bulletin 1(1):1-7.
U.S. Code. Title 21. Sec. 802.
U.S. Code. Title 21. Sec. 826.
U.S. House of Representatives. 1970. House Report No. 91-1444. Comprehensive Drug Abuse and Prevention Control Act of 1970.
U.S. v. Evers, 643 F. 2d 1043 (5th Circuit 1981)
Ventafridda, V.; M. Tamburini; A. Caraceni; F. DeConno, and F. Naidi. 1987. A validation study of the WHO method for cancer pain relief. Cancer 59(4):850-856.
Virginia Department of Health Professions. November, 1991. Report on Pharmaceutical drug Diversion in the Commonwealth to the Virginia State Crime Commission.
Von Roenn, J.; C.S. Cleeland; R. Gonin, and K Pandya. 1991. Physician attitudes toward cancer pain and its management. American Society of Clinical Oncology.
Vortherms, R.; R. Ryan, and S. Ward. (in press). Nurse's knowledge of and attitudes toward pharmacologic management of cancer pain.
Ward, S.; N. Goldberg; D. Pawlie-Koonz; V. Miller-McCauley; C. Mueller; A. Nolan; A. Robbins; D. Stormoen, and D. Weissman. (in review). Patient-related barriers to management of cancer pain.
Washington State Medical Disciplinary Board. August, 1989. Policy Statement. State of Washington Department of Health.
Weintraub, M.; S. Singh; L. Byrne; K Maharaj, and L. Guttmacher. 1991. Consequences of the 1991 New York State triplicate benzodiazepine prescription regulations. Journal of the American Medical Association 266(17):2392-2397.
Weissman, D.E., and J.D. Haddox. 1989. Opioid pseudoaddiction - an iatrogenic syndrome. Pain 36:363-366.
Weissman, D.E.; D.E. Joranson, and M.B. Hopwood. 1991. Wisconsin physicians' knowledge and attitudes about opioid analgesic regulations. Wisconsin Medical Journal December 1991.
Weissman, D.E.; S.L. Burchman; PA. Dinndorf, and J.L. Dahl. 1992. Handbook of Cancer Pain Management (Third edition), Wisconsin Cancer Pain Initiative.
Wisconsin Controlled Substances Board. 1986. Protecting your medical practice. A Guide to Prescribing Controlled Substances in Wisconsin. State of Wisconsin, Department of Health and Social Services, Controlled Substances Board.
Wisconsin Controlled Substances Board. 1988. Annual report of the Controlled Substances Board 1987. State of Wisconsin, Department of Health and Social Services, Controlled Substances Board.
Wood, M.M., and M.J. Cousins. 1989. Iatrogenic neurotoxicity in cancer patients. Pain 39:1-3.
World Health Organization. 1986. Cancer pain relief. Geneva, Switzerland.
_____. 1990. Cancer pain relief and palliative care. Report of a WHO expert committee. Geneva, Switzerland.
_____. 1991. Cancer Pain Release. World Health Organization Collaborating Center for Symptom Evaluation in Cancer Care, University of Wisconsin, Madison, WI. 5(1): February.
_____. 1992. Cancer Pain Release. World Health Organization Collaborating Center for Symptom Evaluation in Cancer Care, University of Wisconsin, Madison, WI. 6(1): Spring.