The Placebo Effect in Alternative Medicine: Can the Performance of a In alternative medicine, the main question regarding placebo has …
COMPLEMENTARY AND ALTERNATIVE MEDICINE SERIES Series Editors: David M Eisenberg, MD, and Ted J Kaptchuk, OMD
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The Placebo Effect in Alternative Medicine: Can the Performance of a Healing Ritual Have Clinical Significance?
Ted J Kaptchuk, OMD
In alternative medicine, the main question regarding placebo has been whether a given therapy has more than a placebo effect Just as mainstream medicine ignores the clinical significance of its own placebo effect, the placebo effect of unconventional medicine is disregarded except for polemics This essay looks at the placebo effect of alternative medicine as a distinct entity This is done by reviewing current knowledge about the placebo effect and how it may pertain to alternative medicine The term placebo effect is taken to mean not only the narrow effect of a dummy intervention but also the broad array of nonspecific effects in the patient physician relationship, including attention; compassionate care; and the modulation of
expectations, anxiety, and self-awareness Five components of the placebo effect–patient, practitioner, patientpractitioner interaction, nature of the illness, and treatment and setting–are examined
Therapeutic patterns that heighten placebo effects are especially prominent in unconventional healing, and it seems possible that the unique drama of this realm may have enhanced placebo effects in particular conditions Ultimately, only prospective trials directly comparing the placebo effects of unconventional and mainstream medicine can provide reliable evidence to support such claims Nonetheless, the possibility of enhanced placebo effects raises complex conundrums Can an alternative ritual with only nonspecific psychosocial effects have more positive health outcomes than a proven, specific conventional treatment? What makes therapy legitimate, positive clinical outcomes or culturally acceptable methods of attainment? Who decides?
Ann Intern Med 2002;136:817-825 For the author
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fficacious therapy, in one biomedical definition, is therapy that has positive effects greater than those of an indistinguishable dummy treatment in a randomized, controlled trial RCT 13 Such specific efficacy is actually a comparative measure: intervention contrasted with placebo This relative effectiveness, which is estimated by statistical testing, is taken to indicate authenticity The clinical significance, that is, the outcome measured by using the patients original condition as a baseline, is usually a secondary consideration for determining legitimate medical interventions Any clinical impact due to the placebo, which is deemed to lack truthfulness, is even less notable and is valued only as a comparison baseline for genuine effects 3 Specific effects are by definition superior to nonspecific effects The clinical repercussions of the placebo are tolerated as necessary nuisance noise but are otherwise considered
inconsequential or treated with contempt 4 Given the privileged status of specific effects, it is not surprising that the clinical impact of alternative medicines placebo effects are routinely ignored 5 The only serious question has been whether alternative medicine has more than a placebo effect Discarding all placebo effects in a single trash basket of untruthfulness, however, diminishes our knowledge of important dimensions of health care This essay examines the neglected clinical significance of the placebo effect in alter-
E
native medicine and raises the possibility that some types of unconventional medicine may produce placebo outcomes that are dramatic and, from the patients perspective, especially compelling The term placebo effect is taken to mean not only the narrow effect of an imitation intervention but also the broad amalgam of nonspecific effects present in any patientpractitioner relationship, including attention; communication of concern; intense monitoring;
diagnostic procedures; labeling of complaint; and alterations produced in a patients expectancy, anxiety, and relationship to the illness This essay asks whether alternative medicine can have an enhanced placebo effect In some conditions, can any of alternative medicines particular rituals have a greater impact than the rituals of conventional medicine or than a proven physiologically active treatment? After all, as many of the examples in this essay will demonstrate, two interventions may have different effects on patient outcome even though both [are] equivalent to placebo in clinical trials 6 Dismissing a treatment as just a placebo may not be enough Alternative medicine may be an especially successful placebo-generating health care system Rather than specific biological consequences, which epidemiologists designate as fastidious efficacy 7, alternative medicine may administer an especially large dose of what anthropologists call performative efficacy 8 Performative
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College of PhysiciansAmerican Society of Internal Medicine 817
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The Placebo Effect in Alternative Medicine
efficacy relies on the power of belief, imagination, symbols, meaning, expectation, persuasion, and self-relationship This essay takes five components of the placebo drama–patient, practitioner, patientpractitioner interaction, nature of the illness, and treatment and setting– and examines their placebogenic potentials in unconventional healing practices Much of the evidence is derived from conventional research and is speculatively applied to alternative medicine Also, it should be noted that most of the placebo research discussed in this essay does not represent an artifactual placebo effect explainable by natural history or regression to the mean Rather, it usually involves comparative experiments with two different types of placebo or the same placebo delivered under different cognitive or emotional circumstances where two distinct placebo outcomes
would not support the idea of placebo effect as only natural history Finally, this essay argues mostly in generalities Obviously, the placebo effect is likely to be at least as heterogeneous in alternative medicine as in conventional medicine, but it is hoped that raising these questions will encourage further discussion and research
PATIENT CHARACTERISTICS Although the patient is the protagonist in the placebo drama, research has failed to find consistent placebo responders or to identify personality traits or other qualities of persons who frequently react to placebo 9 11 However, evidence shows that patient expectations influence outcomes of both placebo and active treatment Asthmatic patients who believe that an inert substance is a bronchodilator or a bronchoconstrictor respond accordingly 1214 In a small but classic crossover experiment, healthy volunteers received a placebo pill in which a magnet was embedded In random order, at different times, they were told that they were
receiving a relaxant, a stimulant, or a placebo Subsequent gastric motility was significantly consistent with patients expectations 15 Patient expectancies also significantly change or even reverse the actions of many potent pharmaceutical agents 16 19 Adherence to placebo may also be a surrogate marker for a patients own contribution to the activation of the placebo response 20, 21 In RCTs, such placebo adherence effects–the post hoc differences observed in the placebo arm between those who comply
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with taking placebo and those who do not–are associated not only with symptom relief but also with concrete end points, including survival 2224 Indeed, differences in adherence are associated with differences in outcomes that exceed the effects of many pharmaceutical agents 25 Patient preferences for one type of intervention, especially in participative interventions for example, exercise or diet programs, may contribute
significantly to outcomes, including increased placebo responses 26 28 In contrast to conventional medicine, with its measured objectivity, alternative medicine offers a charged constellation of expectations Alternative medicines romantic vision is inhabited by benevolent and intentional forces for example, the innate intelligence of chiropractic or the qi of acupuncture that are unrestrained by the laws of normative physics 29 An exaggerated notion of the possible readily elicits patients magical anticipation These unconventional concepts do not require absolute belief in the sense that their truth value is certified by logic or argument but rather requires moderate openness in the sense that they are taken into the imagination and lived with, if only for a time 30 Alternative medicine emphasizes personal responsibility, which can facilitate adherence Indeed, the act of switching to another medical system and exhibiting preference by action demonstrates an openness to active
participation and adherence and possibly enhances it Paying out-of-pocket and other signs of commitment, such as following daily lifestyle regimens, undoubtedly marshal adherence effects The reasons that patients choose alternative medicine may also potentiate a placebo response Patients with chronic diseases often turn to unconventional healing after long-term negative conditioning with mainstream medicine 31 In this situation, patients hope based on no previous experience with alternative medicine may provide an opportunity for deconditioning from previous unsuccessful medical experiences
PRACTITIONER CHARACTERISTICS The practitioner-healer must expertly play the role of heroic rescuer to facilitate a placebo effect 32 Numerous RCTs have compared optimistic or enthusiastic physician attitudes toward drug or placebo with neutral or doubtful physician attitudes Practitioners have had
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significant impact on
such clinical conditions as pain 3336, psychiatric illness 37 41, hypertension 42, 43, obesity 44, and perimenopause symptoms 45 Although some studies have shown no effect of physicians expectations on clinical end points 46 48, a systematic review of 85 studies found that although more research is needed, provider-induced expectancies are a mechanism for placebo effects, [which have] received support across a range of clinical areas in a variety of studies 49 A second review, which used more stringent entry criteria, found 25 RCTs that examined the impact of randomly assigning patients with physical illnesses to different levels of expectancy and emotional support Although researchers found inconsistent effects and determined that further research was needed, they also found that enhancing patients expectations through positive information about the treatment or illness, while providing support or reassurance, [seemed to] significantly influence health outcomes 50 Even in blinded
RCTs, practitioner certitude seems to influence the magnitude of the placebo effect In one RCT that simultaneously compared two double-blind RCTs, dental patients in one trial received placebo, narcotic analgesics, or narcotic antagonists and those in the other trial received only a placebo or a narcotic antagonist Dentists knew the possible interventions in both trials but remained blinded to administration of medication Pain in placebo recipients was significantly worse in the second trial, in which narcotic drugs were not an option, than in the first trial 51 An earlier RCT of the effect of physician expectations on hypertension drugs also found that practitioner belief can transform outcomes 52 Practitioners of unconventional medicine are less restrained by scientific objectivity than practitioners of conventional medicine The sensibilities of alternative practitioners are therefore often more optimistic and positive than those of their mainstream counterparts 53 The
characteristics thought to enhance the placebo effect and any active intervention seem to be fully operational in the offices of alternative medicine
PATIENTPRACTITIONER INTERACTION The placebo drama is probably more successful if the patient and practitioner find each others beliefs and actions mutually credible or at least intriguing Reciprowwwannalsorg
cal expectations need to be negotiated and joined in the patientphysician duet Many studies indicate that the patientpractitioner encounter is a potent factor in health outcomes 54 56 and that for many nonlifethreatening illnesses, clear diagnosis, assurance of recovery, opportunity for dialogue, and physicianpatient agreement about the nature of the problem hasten recovery or relief 57, 58 One study examined 200 patients who presented to general practitioners with symptoms but no abnormal physical signs and in whom no definite diagnosis could be made Patients were randomly assigned in a 2 2 design to treatment or no treatment and
to a positive consultation, in which they received a firm diagnosis and [were] told confidently that [they] would be better in a few days, or a negative consultation, in which they were told that their condition was uncertain Although provision of treatment made no difference, positive interaction produced significantly faster recovery 59 A similar experiment in 100 patients with acute tonsillitis had analogous results 60 Consultation in unconventional medicine is more likely than its mainstream counterpart to produce a precise diagnosis that matches patients perceptions In unconventional medicine, patient experience is never devalued or brushed aside as unreliable 61 Inevitably, since the alternative world is not as constrained by the dichotomy of objectivity and subjectivity, the chiropractor will find the subluxation, the acupuncturist will detect the yinyang disharmony, and the health food advocate will identify the transgression that makes sense of the patients life-world In
addition, if a patient is new to alternative medicine, an opportunity for exchange is invariably offered, providing the patient with theoretical explanations designed to take the mystery out of process and problems 62 When it is considered that 40 to 60 of patients may never receive a firm diagnosis in conventional medicine 63, 64, an alternative diagnosis may be a potent form of nonspecific healing that changes the circumstances under which the patient exists 65 67, including reducing the dysphoria of uncertainty 68 Besides diagnosis, the healing encounter also establishes therapeutic goals Paradoxically, while the alternative diagnosis tends to be precise, treatment aims can be diverse Because of such notions as holistic medicine and body, mind, spirit, alternative medicine can have extremely broad, indeterminate therapeutic targets and
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therefore, at
least from a cultural view, in some sense cannot fail 69 Such amorphous goals can provide additional maneuvering room for positive progress, or at least incremental change 70 If the patients symptoms do not directly improve, it is likely that something positive will happen and be attributed to the intervention even if the change pertains only to alternative constructs, such as the homeopathic spiritual force or the acupuncture qi Taken together, the alternative diagnosis, prognosis, and treatment aims serve to regulate symptom intensity and distress and create enough certainty to diminish the threat of the inchoate while preserving enough ambiguity to allow for fresh improvisation 71
THE NATURE OF THE ILLNESS The placebo effect may benefit from the types of illnesses that alternative medicine commonly treats Data indicate that the overwhelming majority of medical conditions treated by unconventional medicine fall into the following categories: highly subjective symptoms lacking
identifiable physiologic correlates, chronic conditions with a fluctuating course often influenced by selective attention, and affective disorders 2, 72 Not surprisingly, these conditions are precisely those that researchers believe are especially susceptible to inordinately strong placebo responses: back and chronic pain 7375, fatigue 76, 77, arthritis 78, 79 headache 80, 81, allergies 82, 83, hypertension in some situations 84, 85, insomnia 86, 87, asthma 13, 88, chronic digestive disorders 89, 90 depression 91, 92, and anxiety 93 Even researchers who question the existence or significance of a placebo effect–at least in the narrow sense of the outcome produced by a dummy intervention– concede its impact when outcomes are continuous and subjective 94 Also, persons with self-limiting diseases, such as the common cold and sprains and strains, also frequently use alternative medicine In these cases, the natural course of the disease undoubtedly creates the appearance of treatment
response and enhances the perception of unconventional medicines effectiveness TREATMENT AND SETTING Treatment paraphernalia and setting affect the impact of a placebo performance For placebo pills, a regimen of four times per day seems more effective than a regimen of twice per day 95 A brand-name therapy that includes
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either active or inert ingredients may often yield better results than an identical treatment that is not as well known 96, and devices or elaborate procedures can have greater placebo effects than pills 97, 98 Active placebos placebos containing medications, such as atropine, that are ineffective for the condition being studied but produce recognizable drug-related side effects seem to provide genuine treatment recognition that leads to heightened placebo effects 99, 100 With good showmanship, a well-designed, totally inert stage prop can offer this kind of feedback loop and can produce exaggerated
placebo effects Two RCTs– one of transcutaneous electrical nerve stimulation and one of placebo electronic machines– demonstrated that, with good staging, blank machines can provide feedback sensations In the first study, all patients reported an electrical sensation after adjustment of the dummy apparatus, which was equipped with visual and sound feedback 101 In the second trial which used only dummy machines under two different sets of expectations, a significant number of participants felt the nonexistent current, and some even volunteered that the sensation was just amazing 102 Biomedicine and alternative medicine each have a special allure of mystery and exotic power; it would be hard to argue that one backdrop consistently provides a superior placebo effect However, alternative medicine has the advantage of always having an intervention scenario Therapeutic passivity is rarely an option, and practitioners can, at a minimum, offer something that is likely to have a placebo
effect In some situations, and at least for continuous subjective outcomes, an intervention presumably has a greater effect than no treatment 94, 103 Also, to demonstrate active intervention, alternative medicine treatments have unique feedback loops that are likely to facilitate, if not heighten, substantial placebo responses For example, chiropractic adjustment often triggers an audible pop so that the patient can hear the subluxation being fixed 104, acupuncturists propagate a sensation of vital energy coursing through invisible meridians 105, and psychic healers summon tingling vibrations 106
DOES ALTERNATIVE MEDICINE HAVE ENHANCED PLACEBO EFFECTS? Despite the arguments and speculations already presented, there is scant empirical evidence that any particwwwannalsorg
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ular type of alternative medicine used for any particular condition has an augmented placebo effect Even concerning the placebo effect in general, the
evidence cited earlier is often methodologically weak and limited by small numbers and short follow-up periods Some social scientists argue that for the believer in science, medical care that appears to be scientific would provide a superior placebo; for the believer of whatever other cultural system of meaning and values, alternative medicine may provide a superior placebo 107 Perhaps biomedicines effort to eliminate ritual or placebo interventions itself produces an improved placebo effect Two examples from RCTs may help readers concretely envision an enhanced placebo effect In a fourarm crossover RCT involving 44 patients with chronic cervical osteoarthritis of more than 6 months duration, acupuncture, sham acupuncture, and diazepam were all equivalent and were superior to a placebo pill 108 In this study, the outcome of the ritual of acupuncture real and sham acupuncture were not different equaled the outcome of an effective drug In a second RCT, which studied spinal
manipulation, 256 patients with nonspecific back and neck disorders were randomly assigned to receive manual therapy the Dutch equivalent of chiropractic, physical therapy, placebo-device therapy with a detuned ultrasonography machine and detuned short-wave diathermy that emitted sounds and lights, or treatment from a general practitioner 109 Six weeks of manual therapy and physical therapy were equally and significantly better than the sham machine, which significantly outperformed the general practitioner It cannot be determined whether the manual and physical therapies had specific treatment effects or simply yielded better placebo effects than the inanimate gadget Nonetheless, in this experiment, treatment with a sham machine surpassed treatment from a competent physician for relief of low back pain To more rigorously test these possible relative nonspecific effects, my colleagues and I are performing a National Institutes of Healthfunded RCT that randomly assigns patients with
chronic pain to one of two parallel run-in phases Before entering two subsequent RCTs, one run-in group receives a conventional-appearing placebo pill and the other receives an alternative medicine sham procedure; the main goal of the run-in phases is to detect differing placebo effects 97 Any confident assertion about a placebo effect enhanced by
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alternative medicine would probably require many such experiments Some may dismiss these types of investigation as useless After all, a placebo is just a placebo Others would argue that such avoidance impoverishes and narrows the understanding of what patients receive from alternative medicine and, by extension, conventional medicine Even those who doubt the existence or significance of a narrow placebo effect seem open to the possibility of broad placebo effects embedded in the psychosocial context of the patientpractitioner relationship 110, 111
WHAT IS LEGITIMATE HEALING? Besides clinical and scientific value, the question
of enhanced placebo effects raises complex ethical questions concerning what is legitimate healing What should determine appropriate healing, a patients improvement from his or her own baseline clinical significance or relative improvement compared with a placebo fastidious efficacy? As one philosopher of medicine has asked, are results less important than method 3? Both performative and fastidious efficacy can be measured Which measurement represents universal science? Which measurement embodies cultural judgment on what is correct healing? Are the concerns of the physician identical to those of the patient? Is denying patients with nonspecific back pain treatment with a sham machine an ethical judgment or a scientific judgment? Should a patient with chronic neck pain who cannot take diazepam because of unacceptable side effects be denied acupuncture that may have an enhanced placebo effect because such an effect is bogus? Who should decide? Patients attitudes toward placebo
interventions especially enhanced interventions probably differ from physicians attitudes 112 This distinction is probably most evident in surgery, another field in which a heightened placebo effect is possible 97, 113, as illustrated by two RCTs that tested implantation of fetal dopaminergic cells for Parkinson disease Patients with Parkinson disease seem to have a robust placebo response 114, 115; the biochemical substrate of this response in relation to the release of dopamine in the striatum has recently been shown on positron emission tomography 116 At the conclusion of one of the two RCTs,
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patients were unblinded, and half were told they had received sham surgery that had performed the same as real surgery In the early reports from this study, both groups experienced significant clinical improvement The subsequent full report, which included
long-term data, reported a less durable placebo effect [117] When patients who had received the sham surgery were told that they could not receive the real but now discredited surgery, as they had been promised in the informed consent form, 70 were disappointed or outraged because of the dramatic benefits they had already received from sham surgery 118 120 They wanted the real procedure even if it was equivalent to the sham Of interest, the second RCT, which also found no difference between active and imitation surgery, demonstrated a stable and significant placebo effect after 18 months 121 For many patients, performative efficacy may be more critical than fastidious efficacy Obviously, this illustration is not meant to advocate ritualistic surgery Rather, it is meant to highlight the complex relationship among clinical, scientific, and ethical judgments
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CONCLUSION Alternative medicine may be composed of healing rituals that have especially potent performative efficacy Therapeutic characteristics that may enhance placebo effects seem especially prominent in unconventional healing Although more research into this question is necessary before any such assertion can be made with confidence, an enhanced placebo effect raises complex questions about what is legitimate therapy, and who decides
From Harvard Medical School, Boston, Massachusetts
Acknowledgment: The author thanks Robb Scholten, June Cobb, Pat
Wilkinson, John C Wilson, Maria Van Rompay, and Marcia Rich for editorial and research assistance
Grant Support: In part by the National Institutes of Health
1R01AT00402-01, U24 AR43441, and
1R21AT00553, the John E Fetzer Institute, the Waletzky Charitable Trust, the Friends of Beth Israel Deaconess Medical Center, and American Specialty Health Plan
Requests for Single Reprints: Ted J Kaptchuk, OMD, Beth Israel
Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215
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effects in pain treatment and research JAMA 1994;271:160914 [PMID: 7880221] 74 Wall PD Pain and the placebo response In: Bock G, Marsh J, eds Experimental and Theoretical Studies of Consciousness Ciba Foundation Symposium 174 New York: J Wiley; 1993 75 McQuay H, Carroll D, Moore A Variation in the placebo effect in randomised controlled trials of analgesics: all is as blind as it seems Pain 1996;64:331-5 [PMID: 8740611] 76 Lasagna L, Laties VG, Dohan JL Further studies on the pharmacology of placebo administration J Clin Invest 1958;37:533-7 77 Brodeur DW The effects of stimulant and tranquilizer placebos on healthy subjects in a real-life situation Psychopharmacologia 1965;7:444-52 [PMID: 4378577] 78 Morison RA, Woodmansey A, Young AJ Placebo responses in an arthritis trial Ann Rheum Dis 1961;20:178-85 79 Pillemer SR, Fowler SE, Tilley BC, Alarcon GS, Heyse SP, Trentham DE, et al Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial MIRA Trial Group
Minocycline in Rheumatoid Arthritis Arthritis Rheum 1997;40:419-25 [PMID: 9082927] 80 Couch JR Jr Placebo effect and clinical trials in migraine therapy Neuroepidemiology 1987;6:178-85 [PMID: 3317098] 81 Diener HC, Dowson AJ, Ferrari M, Nappi G, Tfelt-Hansen P Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials Cephalalgia 1999;19:699-700 [PMID: 10570722] 82 Kagan G, Dabrowicki E, Huddlestone L, Kapur TR, Wolstencroft P A double blind trial of terfenadine and placebo in hay fever using a substitution technique for non-responders J Int Med Res 1980;8:404-7 [PMID: 6108264] 83 DSouza MF, Emanuel MB, Gregg J, Charlton J, Goldschmidt J A method for evaluating therapy for hay fever A comparison of four treatments Clin Allergy 1983;13:329-35 [PMID: 6411382] 84 Preston RA, Materson BJ, Reda DJ, Williams DW Placebo-associated blood pressure response and adverse effects in the treatment of hypertension: observations
from a Department of Veterans Affairs Cooperative Study Arch Intern Med 2000;160:1449-54 [PMID: 10826457] 85 Suchman AL, Ader R Classic conditioning and placebo effects in crossover studies Clin Pharmacol Ther 1992;52:372-7 [PMID: 1424409] 86 Storms MD, Nisbett RE Insomnia and the attribution process J Pers Soc Psychol 1970;16:319-28 [PMID: 5479134] 87 Bootzin RR, Herman CP, Nicassio P The power of suggestion: another examination of misattribution and insomnia J Pers Soc Psychol 1976;34:673-9 [PMID: 993978] 88 Godfrey S, Silverman M Demonstration by placebo response in asthma by means of exercise testing J Psychosom Res 1973;17:293-7 [PMID: 4206466] 89 Moerman DE Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure Med Anthropol Q 2000;14:51-72 [PMID: 10812563] 90 Ilnyckyj A, Shanahan F, Anton PA, Cheang M, Bernstein CN Quantifi824 4 June 2002 Annals of Internal Medicine Volume 136 Number 11
cation of the placebo response in ulcerative colitis
Gastroenterology 1997;112: 1854-8 [PMID: 9178676] 91 Brown WA, Johnson MF, Chen MG Clinical features of depressed patients who do and do not improve with placebo Psychiatry Res 1992;41:203-14 [PMID: 1594707] 92 Kirsch I, Sapirstein G Listening to Prozac but hearing placebo: a metaanalysis of antidepressant medications In: Kirsch I, ed How Expectancies Shape Experience Washington, DC: American Psychological Assoc; 1999 93 Rosenberg NK, Mellergård M, Rosenberg R, Beck P, Ottosson JO Characteristics of panic disorder patients responding to placebo Acta Psychiatr Scand Suppl 1991;365:33-8 [PMID: 1862732] 94 Hrobjartsson A, Gøtzsche PC Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment N Engl J Med 2001;344: 1594-602 [PMID: 11372012] 95 de Craen AJ, Moerman DE, Heisterkamp SH, Tytgat GN, Tijssen JG, Kleijnen J Placebo effect in the treatment of duodenal ulcer Br J Clin Pharmacol 1999;48:853-60 [PMID: 10594490] 96 Branthwaite A, Cooper P Analgesic
effects of branding in treatment of headaches Br Med J Clin Res Ed 1981;282:1576-8 [PMID: 6786566] 97 Kaptchuk TJ, Goldman P, Stone DA, Stason WB Do medical devices have enhanced placebo effects? J Clin Epidemiol 2000;53:786-92 [PMID: 10942860] 98 de Craen AJ, Tijssen JG, de Gans J, Kleijnen J Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos J Neurol 2000;247:183-8 [PMID: 10787112] 99 Moncrieff J, Wessely S, Hardy R Meta-analysis of trials comparing antidepressants with active placebos Br J Psychiatry 1998;172:227-31 [PMID: 9614471] 100 Fisher S, Greenberg RP How sound is the double-blind design for evaluating psychotropic drugs? J Nerv Ment Dis 1993;181:345-50 [PMID: 8501455] 101 Marchand S, Charest J, Li J, Chenard JR, Lavignolle B, Laurencelle L Is TENS purely a placebo effect? A controlled study on chronic low back pain Pain 1993;54:99-106 [PMID: 8378107] 102 Schwitzgebel RK, Traugott M Initial note on the placebo effect of
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The Placebo Effect in Alternative Medicine
Academia and Clinic
111 Hrobjartsson A, Gøtzsche PC Core belief in powerful effects of placebo interventions is in conflict with no evidence of important effects in a large systematic review Advances in Mind-Body Medicine 2001;17:312-8 112 Lynoe N, Mattsson B, Sandlund M The attitudes of patients and physi cians towards placebo treatment–a comparative study Soc Sci Med 1993;36: 767-74 [PMID: 8480221] 113 Johnson AG Surgery as a placebo Lancet 1994;344:1140-2 [PMID: 7934500] 114 Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D The placebo response in Parkinsons disease Parkinson Study Group Clin Neuropharmacol 1999;22:207-12 [PMID: 10442249] 115 Goetz CG, Leurgans S, Raman R, Stebbins GT Objective changes in
motor function during placebo treatment in PD Neurology 2000;54:710-4 [PMID: 10680808] 116 de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ Expectation and dopamine release: mechanism of the placebo effect in
Parkinsons disease Science 2001;293:1164-6 [PMID: 11498597] 117 Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, et al Transplantation of embryonic dopamine neurons for severe Parkinsons disease N Engl J Med 2001;344:710-9 [PMID: 11236774] 118 Husten L Fetal-cell-implantation trial yields mixed results Lancet 1999; 353:1501 119 Macklin R The ethical problems with sham surgery in clinical research N Engl J Med 1999;341:992-6 [PMID: 10498498] 120 Johannes L Sham surgery is used to test effectiveness of novel operations Wall Street Journal 1998;11 December:A1, A8 121 Watts RL, Freeman RA, Hauser RA, Bakay SA, Ellias AJ, Stoessl AJ, et al A double-blind, randomized, controlled, multicenter clinical trial of the safety and efficacy of
stereotaxic intrastriatal implantation of fetal porcine ventral mesencephalic tissue NeurocellTM-PD vs imitation surgery in patients with Parkinsons disease PD [Abstract] Parkinsonism and Related Disorders 2001;7 Suppl:S87
Sometimes we no longer know what is true for us, in which direction our own integrity lies Reclaiming ourselves usually means coming to recognize and accept that we have in us both sides of everything We are capable of fear and courage, generosity and selfishness, vulnerability and strength These things do not cancel each other out but offer us a full range of power and response to life Life is as complex as we are One of the blessings of growing older is the discovery that many of the things I once believed to be my shortcomings have turned out in the long run to be my strengths, and other things of which I was unduly proud have revealed themselves in the end to be among my shortcomings What a blessing it is to outlive your self-judgments and harvest your
failures Rachel Naomi Remen, MD Kitchen Table Wisdom: Stories That Heal New York: Riverhead Books; 1996:35-8 Submitted by: George Ho Jr, MD East Carolina University School of Medicine Greenville, NC 27858
Submissions from readers are welcomed If the quotation is published, the senders name will be acknowledged Please include a complete citation along with page number on which the quotation was found, as done for any referenceThe Editor
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