Abstract
A number of organizations have advised against the use of placebo substitution, including the American Pain Society, Agency for Healthcare Policy and Research, World Health Organization, Healthcare Facilities Accreditation Program, Joint Commission on Accreditation of Healthcare Organizations, Education for Physicians on End-of-Life Care Project (cosponsored by the American Medical Association and The Robert Wood Johnson Foundation), American Nursing Association, and the American Society of Pain Management Nurses.
This white paper describes the literature and rationale in support of the American Osteopathic Association's (AOA's) position on the controversial subject of the use of placebos for pain management in terminally ill patients.
The issues of placebo use, placebo effect, and placebo abuse as they affect pain management are fraught with opinion, confusion, and misunderstanding. The placebo effect of medication can be a significant resultant action of any prescription. However, the substitution of a placebo in place of effective pain medication has been widely recognized as unethical, ineffective, and potentially harmful.
1-8(pp37-30)
A
placebo is a substance presumed to be pharmacokinetically inert.
Placebo substitution means the substitution of a physiologically inactive substance for a comparison with the physiologically active substance.
Placebo effect is the positive psychosomatic response of an individual to a treatment.
9 The placebo effect is an important adjunct in the symptomatic treatment of patients. The alleviation of symptoms has an inherent positive psychological component: Patients who perceive their symptoms to be relieved by the treatment and trust in their treating physician's treatment plan or prescription (or both) for the symptom relief are more likely to obtain relief.
2
Placebo responses are necessary for controlled clinical trials in which the patient is informed that a placebo may indeed be used. Physiologic responses to placebo can be pleasant or unpleasant to the patient. An unpleasant psychosomatic effect attributable to administration of a placebo is called a
nocebo response. A pleasant effect is called a
positive placebo response. Jerome
4(p221) notes:
The basis of the placebo effect in a therapeutic physician-patient relationship also involves good communication skills as well as listening to the patient.
4,10,11
To summarize, a placebo is an agent, necessarily used in controlled clinical trials, that has no inherent physiologic action, yet is designed to mimic a therapy with a known active physiologic effect. Positive changes resulting from administration of placebo are due to expectations of success by the patient. Thus, the use of placebo effect is based on the patient's perception of the role of the placebo agent with symptom relief. A positive patient-physician relationship may enhance the placebo effect.
Addiction, Substance Abuse and Dependence, Tolerance, Withdrawal, and Pseudoaddiction
Some physicians inappropriately justify using placebo in pain management to avoid “addicting” the patient.
Addiction, as defined by a consensus document from the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine
12 is Actually, it is rare for a person to develop an addiction to pain medications.
Substance abuse is defined as psychological and physical dependence on substances. Some physicians are concerned that prescribing narcotics may lead to substance abuse and therefore may attempt to use a placebo to assess whether the patient truly requires narcotics for pain relief. However, no scientific basis exists for using placebo in the assessment of the patient in pain who has or may have the potential for a substance abuse. The
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (
DSM-IV),
13 lists definitive criteria for diagnosis of psychological and physical dependence on substances. This text categorizes “Substance-Related Disorders” but does not use the term
addiction; further, nowhere in the
DSM-IV do criteria for diagnosing and treating various forms of substance abuse include the administration of placebos.
Substance dependence is defined as a cluster of cognitive, behavioral, and physiologic symptoms. The essential feature of a substance-dependent individual is continuous use of the substance despite significant substance-related problems such as deleterious effects on occupation, relationships, and health.
Fearing that a patient is manifesting a substance-related disorder, physicians may become uncomfortable with requests for increased dosages of pain medications. A better understanding of the concepts of tolerance, physical dependence, physiologic-dependence withdrawal symptoms, and pseudoaddiction may help physicians understand and more effectively treat these patients.
Tolerance represents a markedly diminished effect that can occur with continued use of most medications; the degree depends on the daily dose and length of use. The need for medication titration, because of either development of tolerance or incomplete responsiveness, is a part of routine medical care. Tolerance occurs as the result of compensatory changes in receptors or increased clearance resulting from induction of various metabolic pathways, or both. The problem of tolerance therefore should be anticipated as a possible outcome in patients treated with prescription pain medications.
Withdrawal is defined by the
DSM-IV13 as a maladaptive behavioral change having physiologic and cognitive concomitants which occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged use of the substance, frequently inappropriately. Examples of withdrawal include the onset of seizures or delirium tremens in a newly abstinent alcohol chemically dependent individual.
Pseudoaddiction is the term used to describe the behavior of a patient in pain who is receiving an insufficient amount or an inappropriate dosing frequency of administration (or both) of the prescribed pain medication. In an effort to obtain relief, the patient in pain will request more frequent or increased medication, or both. Such “drug-seeking behavior” has been deemed as “proof” of “addiction.” The reason for such requests is frequently that the patient is receiving an underdose because of administration of too little of the medication or because of too long a delay between doses of the pain medication, or both. In such instances, the patient receives inappropriate pain relief, which is not an appropriate criterion of a substance-abusing patient according to the
DSM-IV.
13
Although there are no specific laws governing the use of placebos in any circumstance, a considerable amount of legislation exists regarding a patient's right to pain management. Several states have statutes that address this issue. Some of these statutes are based on the Federation of State Medical Boards' (FSMB's)
Model Guidelines for the Use of Controlled Substances for the Treatment of Pain.
14 The FSMB's document clarifies that legislative statutes accepting these guidelines understand the ongoing increased scientific knowledge of pain management and thus have no need to modify legislation as the science of pain management changes. The document does not mention placebo use.
The American Bar Association (ABA)
15 adopted a resolution concerning the promotion of pain management in all patients with chronic pain. This policy resolution states:
Placebo substitution for active pain medicine without informed consent on the part of the patients clearly violates the nature and substance of the ABA's position. Additionally, in two US Supreme Court decisions regarding the right to assisted suicide, the court promoted the right of individuals to appropriate palliative care and pain management.
16,17
Although little case law exists concerning tort or administrative findings against physicians for inadequate pain management, this is likely to change in the near future. The main barrier to malpractice claims for inadequate pain management is use of the customary local standard to determine what constitutes ordinary care. The courts are steadily moving away from this standard to a national standard that uses clinical guidelines as the determinant of ordinary care. This is seen in the decision in the case of Nowatske
v Oserloh, where the court stated, “should customary medical practice fail to keep pace with development and advances in medical science, adherence to custom might constitute a failure to exercise ordinary care.”
18
Guidelines developed by the then Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality),
1 the Healthcare Facilities Accreditation Program,
19 the American Pain Society,
8 as well as the National Pharmaceutical Council and Joint Commission on Accreditation of Healthcare Organizations
20 are good examples of sources the courts are using to determine ordinary practice. These guidelines do not support the use of placebo in any fashion except in approved research studies when the appropriate patient informed consent has been obtained. Therefore, physicians cannot justify the use of placebo for pain management by attempting to diagnose “addiction” or with support from any of the aforementioned regulatory agencies.
5
Furthermore, under California's elder abuse statute,
21 a physician was successfully sued by the deceased's family for inadequate pain management at the end of life.
22
Pain is a universal experience and is subjective by nature. Despite the common colloquialism, “I feel your pain,” no individual can truly experience another's pain. There are no laboratory tests or consistently reliable physical findings for assessing pain. Patient self-report remains the “gold standard” for pain assessment.
23 Use of a placebo in place of an effective pain medication for attempting to determine whether the patient at end of life is really in pain is under no circumstances appropriate.
There is a concern that if a physician deceives the patient and substitutes a placebo treatment in the place of a known effective treatment without informing the patient, the physician-patient relationship will be irreparably damaged. Deception has no place within the therapeutic relationship and is counterproductive. A physician may counsel a patient that “this treatment may be effective in treating your condition,” but evidence-based medicine cannot guarantee a treatment outcome.
In this era of informed consent, deception of the patient poses many problems, including erosion of the trust individuals and society as a whole have in physicians. Methods exist for using placebos and the placebo effect that do not involve deceit, eg, clinical trials or the use of placebo as one of the trial agents for neurolytic block. This one narrow exception uses the placebo trial as part of the treatment selection for neurolytic blockade, a highly specialized procedure performed by a few skilled pain management physicians with appropriate informed consent.
Substituting placebo for accepted forms of pain treatment is undertreating the patient. Undertreatment of patients in pain, as detailed in the ABA's 2000 report,
24 is an ongoing problem. Although placebo efficacy in pain management has been reported, placebo control of pain occurs in fewer patients and for shorter duration than do active pain treatment modalities.
4,8,25
It has also been argued that the prescription of an ineffective placebo in place of effective pain medication can act as a “suicidogen,” whereby individuals in pain who are given inadequate medication for relief may be prompted to hasten their death.
6 In the clinical setting, substitution of a placebo for an active pain medication, even with the consent of the patient, is clinically suspect because better treatment alternatives exist and there are risks associated with the use of placebos. It is therefore inappropriate to substitute a placebo for a medication known to be effective in the treatment of patients with the verified pain of a terminal illness.
Additionally, placebos are associated with side effects
3 and potentially precipitate hyperalgesia
26 or withdrawal in patients previously treated with pain medications.
Exquisite management of end-of-life pain is a medical imperative. Use of a placebo in place of known effective pain medication for determining whether the patient is really in pain is under no circumstances appropriate. Use of placebos does not meet the accepted criteria to diagnose substance abuse, commonly referred to by some physicians as “addiction.” There is no medical justification for the use of placebos to assess or treat patients in pain at end of life.
The only appropriate use of a placebo is in approved clinical research with informed consent.
The Committee would like to thank Frederick J. Goldstein, PhD, FCP, professor of Clinical Pharmacology, Department of Neuroscience, Physiology and Pharmacology; director of Research, MEDNet; and director, Clinical Master of Science Program, Philadelphia College of Osteopathic Medicine, for his contributions to this paper. The Committee would also like to thank Michael A. Seffinger, DO, assistant professor of Family Medicine/Osteopathic Manipulative Medicine, Western University of Health Sciences College of Osteopathic Medicine of the Pacific, Pomona, Calif.