American Osteopathic Association's Position Against

ceive 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 American Osteopathic more likely to obtain relief.2 Association’s Position Placebo responses are necessary for controlled clinical trials in which the Against Use of Placebos patient is informed that a placebo may for Pain Management indeed be used. Physiologic responses in End-of-Life Care to placebo can be pleasant or unpleasant to the patient. An unpleasant psycho- Council on Palliative Care Issues* somatic effect attributable to administration of a placebo is called a nocebo response. A pleasant effect is called a positive placebo response. Jerome4(p221) notes:

A positive placebo response A number of organizations have advised against the use of placebo substitu- simply speaks to the strength of tion, including the American Pain Society, Agency for Healthcare Policy and an individual’s central control pro- Research, World Health Organization, Healthcare Facilities Accreditation Pro- cesses (i.e., mind) to recruit their gram, Joint Commission on Accreditation of Healthcare Organizations, Edu- descending inhibitory system to cation for Physicians on End-of-Life Care Project (cosponsored by the Amer- block pain. The osteopathically ican Medical Association and The Robert Wood Johnson Foundation), American trained physician knows that pain Nursing Association, and the American Society of Pain Management Nurses. relief occurs both in the mind and This white paper describes the literature and rationale in support of the in the body. American Osteopathic Association’s (AOA’s) position on the controversial sub- ject of the use of placebos for pain management in terminally ill patients. The basis of the placebo effect in a The following policy statement was adopted by the AOA’s House of Del- therapeutic physician-patient relation- egates in 2005. This statement was drafted by the association’s Council on Pal- ship also involves good communication liative Care Issues, which at that time was called the End-of-Life Care Com- skills as well as listening to the mittee. patient.4,10,11 This statement has been modified to adhere to the house style of JAOA— To summarize, a placebo is an agent, The Journal of the American Osteopathic Association. necessarily used in controlled clinical trials, that has no inherent physiologic action, yet is designed to mimic a therapy with a known active physio- he issues of placebo use, placebo Definition of Terms logic effect. Positive changes resulting T effect, and placebo abuse as they Placebo Effect, Placebo Substitution, from administration of placebo are due affect pain management are fraught with and Nocebo Response to expectations of success by the patient. opinion, confusion, and misunder- A placebo is a substance presumed to be Thus, the use of placebo effect is based standing. The placebo effect of medica- pharmacokinetically inert. Placebo sub- on the patient’s perception of the role of tion can be a significant resultant action of stitution means the substitution of a phys- the placebo agent with symptom relief. any prescription. However, the substitu- iologically inactive substance for a com- A positive patient-physician relation- tion of a placebo in place of effective pain parison with the physiologically active ship may enhance the placebo effect. medication has been widely recognized as substance. Placebo effect is the positive unethical, ineffective, and potentially psychosomatic response of an individual Addiction, Substance Abuse harmful.1-8(pp37-30) to a treatment.9 The placebo effect is an and Dependence, Tolerance, important adjunct in the symptomatic Withdrawal, and Pseudoaddiction treatment of patients. The alleviation of Some physicians inappropriately justify *For 2004-2005, the members of what is now the symptoms has an inherent positive psy- using placebo in pain management to American Osteopathic Association’s Council on chological component: Patients who per- avoid “addicting” the patient. Palliative Care Issues, were Karen J. Nichols, DO, chair (AOA Board of Trustees); Katherine E. Gal- luzzi, DO, vice-chair; Bruce P. Bates, DO; Benneth Ann Husted, DO; Jimmie P. Leleszi, DO, Cleanne This continuing medical education publication is supported by an educational grant Cass, DO; and Dennis Lavery (National Associa- from Purdue Pharma LP. tions of Osteopathic Foundations’ observer). Ken- neth Simon, DO, was a 2000-2004 member.

American Osteopathic Association • Position Statement on Use of Placebos JAOA • Supplement 4 • Vol 107 • No 6 • June 2007 • ES35 Addiction, as defined by a consensus the assessment of the patient in pain withdrawal symptoms, and pseudoad- document from the American Academy who has or may have the potential for a diction may help physicians understand of Pain Medicine, the American Pain substance abuse. The Diagnostic and Sta- and more effectively treat these patients. Society, and the American Society of tistical Manual of Mental Disorders, Fourth Tolerance represents a markedly Addiction Medicine12 is Edition (DSM-IV),13 lists definitive cri- diminished effect that can occur with teria for diagnosis of psychological and continued use of most medications; the ... a primary, chronic, neurobio- physical dependence on substances. This degree depends on the daily dose and logic disease, with genetic, psy- text categorizes “Substance-Related Dis- length of use. The need for medication chosocial, and environmental fac- orders” but does not use the term addic- titration, because of either development tors influencing its development tion; further, nowhere in the DSM-IV do of tolerance or incomplete responsive- and manifestations. It is charac- criteria for diagnosing and treating var- ness, is a part of routine medical care. terized by behaviors that include ious forms of substance abuse include Tolerance occurs as the result of com- one or more of the following: the administration of placebos. pensatory changes in receptors or impaired control over drug use, Substance dependence is defined as a increased clearance resulting from induc- compulsive use, continued use cluster of cognitive, behavioral, and phys- tion of various metabolic pathways, or despite harm, and craving. iologic symptoms. The essential feature both. The problem of tolerance therefore of a substance-dependent individual is should be anticipated as a possible out- Actually, it is rare for a person to develop continuous use of the substance despite come in patients treated with prescrip- an addiction to pain medications. significant substance-related problems tion pain medications. Substance abuse is defined as psycho- such as deleterious effects on occupation, Withdrawal is defined by the DSM- logical and physical dependence on sub- relationships, and health. IV13 as a maladaptive behavioral change stances. Some physicians are concerned Fearing that a patient is manifesting having physiologic and cognitive con- that prescribing narcotics may lead to a substance-related disorder, physicians comitants which occurs when blood or substance abuse and therefore may may become uncomfortable with tissue concentrations of a substance attempt to use a placebo to assess requests for increased dosages of pain decline in an individual who had main- whether the patient truly requires nar- medications. A better understanding of tained prolonged use of the substance, cotics for pain relief. However, no sci- the concepts of tolerance, physical frequently inappropriately. Examples of entific basis exists for using placebo in dependence, physiologic-dependence withdrawal include the onset of seizures

ES36 • JAOA • Supplement 4 • Vol 107 • No 6 • June 2007 American Osteopathic Association • Position Statement on Use of Placebos or delirium tremens in a newly national standard that uses clin- abstinent alcohol chemically ical guidelines as the determinant dependent individual. of ordinary care. This is seen in the Pseudoaddiction is the term used decision in the case of Nowatske v to describe the behavior of a Oserloh, where the court stated, patient in pain who is receiving “should customary medical prac- an insufficient amount or an inap- tice fail to keep pace with devel- propriate dosing frequency of opment and advances in medical administration (or both) of the pre- science, adherence to custom scribed pain medication. In an might constitute a failure to exer- effort to obtain relief, the patient cise ordinary care.”18 in pain will request more frequent Guidelines developed by the or increased medication, or both. then Agency for Health Care Such “drug-seeking behavior” has Policy and Research (now the been deemed as “proof” of “addic- Agency for Healthcare Research tion.” The reason for such requests and Quality),1 the Healthcare Facil- is frequently that the patient is ities Accreditation Program,19 the receiving an underdose because American Pain Society,8 as well as of administration of too little of the the National Pharmaceutical medication or because of too long Council and Joint Commission on a delay between doses of the pain Accreditation of Healthcare Orga- medication, or both. In such nizations20 are good examples of instances, the patient receives inap- sources the courts are using to propriate pain relief, which is not determine ordinary practice. These an appropriate criterion of a sub- guidelines do not support the use © 2007 Jupiterimages Corporation stance-abusing patient according of placebo in any fashion except to the DSM-IV.13 right of individuals suffering from in approved research studies when the pain to be informed of, choose, and appropriate patient informed consent Legal Considerations in the Use receive effective pain and has been obtained. Therefore, physicians of Placebos in Pain Management symptom evaluation, manage- cannot justify the use of placebo for pain Although there are no specific laws gov- ment, and ongoing monitoring as management by attempting to diagnose erning the use of placebos in any cir- part of basic medical care, even if “addiction” or with support from any cumstance, a considerable amount of such pain and symptom manage- of the aforementioned regulatory agen- legislation exists regarding a patient’s ment may result in analgesic tol- cies.5 right to pain management. Several states erance, physical dependence, or as Furthermore, under California’s elder have statutes that address this issue. an unintended consequence abuse statute,21 a physician was suc- Some of these statutes are based on the shortens the individual’s life. cessfully sued by the deceased’s family Federation of State Medical Boards’ for inadequate pain management at the (FSMB’s) Model Guidelines for the Use of Placebo substitution for active pain end of life.22 Controlled Substances for the Treatment of medicine without informed consent on Pain.14 The FSMB’s document clarifies the part of the patients clearly violates the Adverse Effects of Placebo Use that legislative statutes accepting these nature and substance of the ABA’s posi- Pain is a universal experience and is sub- guidelines understand the ongoing tion. Additionally, in two US Supreme jective by nature. Despite the common increased scientific knowledge of pain Court decisions regarding the right to colloquialism, “I feel your pain,” no indi- management and thus have no need to assisted suicide, the court promoted the vidual can truly experience another’s modify legislation as the science of pain right of individuals to appropriate pal- pain. There are no laboratory tests or management changes. The document liative care and pain management.16,17 consistently reliable physical findings does not mention placebo use. Although little case law exists con- for assessing pain. Patient self-report The American Bar Association cerning tort or administrative findings remains the “gold standard” for pain (ABA)15 adopted a resolution concerning against physicians for inadequate pain assessment.23 Use of a placebo in place of the promotion of pain management in all management, this is likely to change in an effective pain medication for patients with chronic pain. This policy the near future. The main barrier to mal- attempting to determine whether the resolution states: practice claims for inadequate pain man- patient at end of life is really in pain is agement is use of the customary local under no circumstances appropriate. ...the American Bar Association standard to determine what constitutes There is a concern that if a physician urges federal, state, and territorial ordinary care. The courts are steadily deceives the patient and substitutes a governments to support fully the moving away from this standard to a placebo treatment in the place of a

American Osteopathic Association • Position Statement on Use of Placebos JAOA • Supplement 4 • Vol 107 • No 6 • June 2007 • ES37 known effective treatment without Comment 10. Benedetti F, Amanzio M, Casadio C, Oliaro A, Maggi G. Blockade of nocebo hyperalgesia by the informing the patient, the physician- Exquisite management of end-of-life cholecystokinin antagonist proglumide. Pain. patient relationship will be irreparably pain is a medical imperative. Use of a 1997;71:135-140. damaged. Deception has no place within placebo in place of known effective pain 11. Brody H. Placebo response, sustained partner- the therapeutic relationship and is coun- medication for determining whether the ship, and emotional resilience in practice. J Am terproductive. A physician may counsel patient is really in pain is under no cir- Board Fam Pract. 1997;10:72-73. a patient that “this treatment may be cumstances appropriate. Use of placebos 12. American Academy of Pain Medicine, American effective in treating your condition,” but does not meet the accepted criteria to Pain Society, and American Society of Addiction Medicine. Statement on definitions related to the evidence-based medicine cannot guar- diagnose substance abuse, commonly use of opioids for the treatment of pain; 2001. antee a treatment outcome. referred to by some physicians as “addic- Available at: http://www.painmed.org/productpub In this era of informed consent, tion.” There is no medical justification /statements/pdfs/definition.pdf. Accessed March 7, 2005. deception of the patient poses many for the use of placebos to assess or treat 13. American Psychiatric Association. Diagnostic problems, including erosion of the trust patients in pain at end of life. and Statistical Manual of Mental Disorders. ed 4. individuals and society as a whole have The only appropriate use of a placebo Washington, DC: American Psychiatric Association; in physicians. Methods exist for using is in approved clinical research with 1994. placebos and the placebo effect that do informed consent. 14. Federation of State Medical Boards of the not involve deceit, eg, clinical trials or United States, Inc. Model Policy for the Use of Con- trolled Substances for the Control of Pain. May the use of placebo as one of the trial Acknowledgment 2004. Available at: http://www.fsmb.org/Policy% agents for neurolytic block. This one The Committee would like to thank Frederick J. 20Documents%20and%20White%20Papers/2004 narrow exception uses the placebo trial Goldstein, PhD, FCP, professor of Clinical Phar- _model_pain_policy.asp. Accessed March 3, 2005. as part of the treatment selection for neu- macology, Department of Neuroscience, Physi- 15. American Bar Association Resolution. Avail- rolytic blockade, a highly specialized ology and Pharmacology; director of Research, able at: http://www.abanet.org/poladv/congletters/106th/pain091400.html and http://www. procedure performed by a few skilled MEDNet; and director, Clinical Master of Science Program, Philadelphia College of Osteopathic abanet.org/poladv/congletters/106th/pain072800. pain management physicians with html. Accessed March 3, 2005. Medicine, for his contributions to this paper. The appropriate informed consent. Committee would also like to thank Michael A. 16. Vacco, Attorney General of New York v Quill, 000 US 95-1858 (1997). Substituting placebo for accepted Seffinger, DO, assistant professor of Family forms of pain treatment is undertreating Medicine/Osteopathic Manipulative Medicine, 17. Washington v Glucksberg, 000 US 96-110 (1997). the patient. Undertreatment of patients Western University of Health Sciences College of 18. Nowatske v Oserloh. 543 NW 2d 265, 267-72 in pain, as detailed in the ABA’s 2000 Osteopathic Medicine of the Pacific, Pomona, (Wis 1996). 24 report, is an ongoing problem. Calif. 19. Healthcare Facilities Accreditation Program. Although placebo efficacy in pain man- Accreditation Requirements for Healthcare Facili- References ties. Standard 15.01.10. Chicago, Ill: Healthcare agement has been reported, placebo con- Facilities Accreditation Program, American Osteo- 1. Jacox A, Carr DB, Payne R, Berde CB, Breitbart W, trol of pain occurs in fewer patients and pathic Association; February 2005;15-18–15-19. Cain JM, et al. Management of Cancer Pain. Clin- for shorter duration than do active pain ical Practice Guideline No. 9. AHCPR Publication 20. National Pharmaceutical Council and Joint treatment modalities.4,8,25 No. 94-0592. Rockville, Md: Agency for Health Care Commission on Accreditation of Healthcare Orga- It has also been argued that the pre- Policy and Research, US Department of Health and nizations. Pain: Current Understanding of Assess- Human Services, Public Health Service; March 1994. ment, Management and Treatments. December scription of an ineffective placebo in 2001. Available at: http://www.jcaho.org/news place of effective pain medication can 2. Brody H. Commentary on placebos. Hastings +room/health+care+issues/pain+mono_npc. Cent Rep. 1975;5(2):17-18. act as a “suicidogen,” whereby individ- 21. Cal Welf & Inst Code, § 15610.07. uals in pain who are given inadequate 3. Brody H. The lie that heals: the ethics of giving placebos. Ann Intern Med. 1982;97:112-118. 22. Bergman v Eden Medical Center, Cal Super Ct, medication for relief may be prompted No. H205732-1 (2001). to hasten their death.6 In the clinical set- 4. Jerome JA. Pain management. In: Ward RC, executive editor. Foundations for Osteopathic 23. Portenoy RK. Contemporary Diagnosis and ting, substitution of a placebo for an Medicine. 2nd ed. Philadelphia, Pa: Lippincott, Management of Pain in Oncologic and AIDS active pain medication, even with the Williams & Wilkins; 2003:212-226. Patients. Newtown, Pa: Handbooks in Health Care Co; 1998. consent of the patient, is clinically suspect 5. Furrow BR. Pain management and provider lia- because better treatment alternatives bility: no more excuses. J Law Med Ethics. 2001;29 24. American Bar Association. Proposed ABA Policy (1):28-51. on Legal Obstacles To Effective Pain Management. exist and there are risks associated with Adopted July 11, 2000. Available at: http:// www. the use of placebos. It is therefore inap- 6. Goldstein F. Inadequate pain management: a sui- abanet.org/aging/policyfinal.doc. cidogen (Dr. Jack Kevorkian: friend or foe?). J Clin propriate to substitute a placebo for a 25. Emmanuel LL, von Gunten C, Ferris FD. Module Pharmacol. 1997;37:1-3. medication known to be effective in the 4-4: Pain Managment. The Education for Physi- treatment of patients with the verified 7. Porter J, Jick H. Addiction rare in patients treated cians on End-of-Life Care (EPEC) Curriculum: The with narcotics. N Engl J Med. 1980;302:123. EPEC Project. The Robert Wood Johnson Founda- pain of a terminal illness. tion; 1999. Available at: http://www.epec.net Additionally, placebos are associated 8. The Principles of Analgesic Use in the Treat- /EPEC/ Webpages/Ecommerce/itemDetail.cfm? 3 ment of Acute Pain and Cancer Pain. 5th ed. Glen- productID=74. with side effects and potentially pre- view, Ill: American Pain Society; 2003. cipitate hyperalgesia26 or withdrawal in 26. Compton P, Athanasos P, Elashoff D. With- 9. Barsky AJ, Saintfort R, Rogers MP, Borus JF. Non- drawal hyperalgesia after acute opioid physical patients previously treated with pain specific medication side effects and the nocebo dependence in non-addict humans: A preliminary medications. phenomenon. JAMA. 2002;287:622-627. study. J Pain. 2003;4:511-519.

ES38 • JAOA • Supplement 4 • Vol 107 • No 6 • June 2007 American Osteopathic Association • Position Statement on Use of Placebos