COMPLEMENTARY AND ALTERNATIVE MEDICINE SERIES Series Editors: David M. Eisenberg, MD, and Ted J. Kaptchuk, OMD 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 Therapeutic patterns that heighten placebo effects are espe- been whether a given therapy has more than a placebo effect. Just cially prominent in unconventional healing, and it seems possible as mainstream medicine ignores the clinical significance of its that the unique drama of this realm may have “enhanced” pla- own placebo effect, the placebo effect of unconventional medicine cebo effects in particular conditions. Ultimately, only prospective is disregarded except for polemics. This essay looks at the placebo trials directly comparing the placebo effects of unconventional and effect of alternative medicine as a distinct entity. This is done by mainstream medicine can provide reliable evidence to support reviewing current knowledge about the placebo effect and how it such claims. Nonetheless, the possibility of enhanced placebo may pertain to alternative medicine. The term placebo effect is effects raises complex conundrums. Can an alternative ritual with taken to mean not only the narrow effect of a dummy intervention only nonspecific psychosocial effects have more positive health but also the broad array of nonspecific effects in the patient– outcomes than a proven, specific conventional treatment? What physician relationship, including attention; compassionate care; makes therapy legitimate, positive clinical outcomes or culturally and the modulation of expectations, anxiety, and self-awareness. acceptable methods of attainment? Who decides? Five components of the placebo effect—patient, practitioner, patient–practitioner interaction, nature of the illness, and treat- Ann Intern Med. 2002;136:817-825. www.annals.org ment and setting—are examined.
For the author affiliation and current address, see end of text. Efficacious therapy, in one biomedical definition, is native medicine and raises the possibility that some
therapy that has positive effects greater than those of
types of unconventional medicine may produce placebo
an indistinguishable dummy treatment in a randomized,
outcomes that are dramatic and, from the patient’s per-
controlled trial (RCT) (1–3). Such specific efficacy is
spective, especially compelling. The term placebo effect is
actually a comparative measure: intervention contrasted
taken to mean not only the narrow effect of an imitation
with placebo. This relative effectiveness, which is esti-
intervention but also the broad amalgam of nonspecific
mated by statistical testing, is taken to indicate “authen-
effects present in any patient–practitioner relationship,
ticity.” The clinical significance, that is, the outcome
including attention; communication of concern; intense
measured by using the patient’s original condition as a
monitoring; diagnostic procedures; labeling of com-
baseline, is usually a secondary consideration for deter-
plaint; and alterations produced in a patient’s expect-
mining “legitimate” medical interventions. Any clinical
ancy, anxiety, and relationship to the illness. This essay
impact due to the placebo, which is deemed to lack
asks whether alternative medicine can have an “en-
“truthfulness,” is even less notable and is valued only as
hanced” placebo effect. In some conditions, can any of
a comparison baseline for “genuine” effects (3). Specific
alternative medicine’s particular rituals have a greater
effects are by definition superior to nonspecific effects.
impact than the rituals of conventional medicine or than
The clinical repercussions of the placebo are tolerated as
a proven physiologically active treatment? After all, as
necessary nuisance noise but are otherwise considered
many of the examples in this essay will demonstrate,
inconsequential or treated with contempt (4).
“two interventions may have different effects on patient
Given the privileged status of specific effects, it is
outcome even though both [are] equivalent to placebo
not surprising that the clinical impact of alternative
in clinical trials” (6). Dismissing a treatment as “just a
medicine’s placebo effects are routinely ignored (5). The
only serious question has been whether alternative med-
Alternative medicine may be an especially successful
icine has more than a placebo effect. Discarding all pla-
placebo-generating health care system. Rather than spe-
cebo effects in a single trash basket of “untruthfulness,”
cific biological consequences, which epidemiologists des-
however, diminishes our knowledge of important di-
ignate as “fastidious efficacy” (7), alternative medicine
mensions of health care. This essay examines the ne-
may administer an especially large dose of what anthro-
glected clinical significance of the placebo effect in alter-
pologists call “performative efficacy” (8). Performative
2002 American College of Physicians–American Society of Internal Medicine 817
Academia and Clinic The Placebo Effect in Alternative Medicine
efficacy relies on the power of belief, imagination, sym-
with taking placebo and those who do not—are associ-
bols, meaning, expectation, persuasion, and self-relation-
ated not only with symptom relief but also with con-
ship. This essay takes five components of the placebo
crete end points, including survival (22–24). Indeed,
drama—patient, practitioner, patient–practitioner inter-
differences in adherence are associated with differences
action, nature of the illness, and treatment and setting—
in outcomes that exceed the effects of many pharmaceu-
and examines their “placebogenic” potentials in uncon-
tical agents (25). Patient preferences for one type of
ventional healing practices. Much of the evidence is
intervention, especially in participative interventions
derived from conventional research and is speculatively
(for example, exercise or diet programs), may contribute
applied to alternative medicine. Also, it should be noted
significantly to outcomes, including increased placebo
that most of the placebo research discussed in this essay
does not represent an “artifactual” placebo effect ex-
In contrast to conventional medicine, with its mea-
plainable by natural history or regression to the mean.
sured objectivity, alternative medicine offers a charged
Rather, it usually involves comparative experiments with
constellation of expectations. Alternative medicine’s ro-
two different types of placebo or the same placebo de-
mantic vision is inhabited by benevolent and intentional
livered under different cognitive or emotional circum-
forces (for example, the innate intelligence of chiroprac-
stances where two distinct placebo outcomes would not
tic or the qi of acupuncture) that are unrestrained by the
support the idea of placebo effect as only natural history.
laws of normative physics (29). An exaggerated notion
Finally, this essay argues mostly in generalities. Obvi-
of the possible readily elicits patients’ magical anticipa-
ously, the placebo effect is likely to be at least as heter-
tion. These unconventional concepts do not require ab-
ogeneous in alternative medicine as in conventional
solute belief “in the sense that their truth value is certi-
medicine, but it is hoped that raising these questions
fied by logic or argument” but rather requires moderate
will encourage further discussion and research.
openness “in the sense that they are taken into the imag-ination and lived with, if only for a time” (30).
Alternative medicine emphasizes personal responsi-
PATIENT CHARACTERISTICS
bility, which can facilitate adherence. Indeed, the act of
Although the patient is the protagonist in the pla-
switching to another medical system and exhibiting
cebo drama, research has failed to find consistent pla-
preference by action demonstrates an openness to active
cebo responders or to identify personality traits or other
participation and adherence and possibly enhances it.
qualities of persons who frequently react to placebo (9 –
Paying out-of-pocket and other signs of commitment,
11). However, evidence shows that patient expectations
such as following daily lifestyle regimens, undoubtedly
influence outcomes of both placebo and active treat-
marshal adherence effects. The reasons that patients
ment. Asthmatic patients who believe that an inert sub-
choose alternative medicine may also potentiate a pla-
stance is a bronchodilator or a bronchoconstrictor re-
cebo response. Patients with chronic diseases often turn
spond accordingly (12–14). In a small but classic
to unconventional healing after long-term negative con-
crossover experiment, healthy volunteers received a pla-
ditioning with mainstream medicine (31). In this situa-
cebo pill in which a magnet was embedded. In random
tion, patients’ hope (based on no previous experience
order, at different times, they were told that they were
with alternative medicine) may provide an opportunity
receiving a relaxant, a stimulant, or a placebo. Subse-
for “deconditioning” from previous unsuccessful medi-
quent gastric motility was significantly consistent with
patients’ expectations (15). Patient expectancies also sig-nificantly change or even reverse the actions of manypotent pharmaceutical agents (16 –19). PRACTITIONER CHARACTERISTICS
Adherence to placebo may also be a surrogate
The practitioner-healer must expertly play the role
marker for a patient’s own contribution to the activation
of heroic rescuer to facilitate a placebo effect (32). Nu-
of the placebo response (20, 21). In RCTs, such “place-
merous RCTs have compared optimistic or enthusiastic
bo adherence effects”—the post hoc differences ob-
physician attitudes toward drug or placebo with neutral
served in the placebo arm between those who comply
or doubtful physician attitudes. Practitioners have had
818 4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 www.annals.org
The Placebo Effect in Alternative Medicine Academia and Clinic
significant impact on such clinical conditions as pain
cal expectations need to be negotiated and joined in the
(33–36), psychiatric illness (37– 41), hypertension (42,
patient–physician duet. Many studies indicate that the
43), obesity (44), and perimenopause symptoms (45).
patient–practitioner encounter is a potent factor in
Although some studies have shown no effect of physi-
health outcomes (54 –56) and that for many non–life-
cians’ expectations on clinical end points (46 – 48), a
threatening illnesses, clear diagnosis, assurance of recov-
systematic review of 85 studies found that although
ery, opportunity for dialogue, and physician–patient
more research is needed, provider-induced “expectancies
agreement about the nature of the problem hasten re-
are a mechanism for placebo effects, [which have] re-
covery or relief (57, 58). One study examined 200 pa-
ceived support across a range of clinical areas in a variety
tients who presented to general practitioners with symp-
of studies” (49). A second review, which used more
toms but no abnormal physical signs and in whom no
stringent entry criteria, found 25 RCTs that examined
definite diagnosis could be made. Patients were ran-
the impact of randomly assigning patients with physical
domly assigned in a 2 ϫ 2 design to treatment or no
illnesses to different levels of expectancy and emotional
treatment and to a positive consultation, in which they
support. Although researchers found inconsistent effects
received “a firm diagnosis and [were] told confidently
and determined that further research was needed, they
that [they] would be better in a few days,” or a negative
also found that “enhancing patients’ expectations
consultation, in which they were told that their condi-
through positive information about the treatment or ill-
tion was uncertain. Although provision of treatment
ness, while providing support or reassurance, [seemed
made no difference, positive interaction produced signif-
to] significantly influence health outcomes” (50).
icantly faster recovery (59). A similar experiment in 100
Even in blinded RCTs, practitioner certitude seems
patients with acute tonsillitis had analogous results (60).
to influence the magnitude of the placebo effect. In one
Consultation in unconventional medicine is more
RCT that simultaneously compared two double-blind
likely than its mainstream counterpart to produce a pre-
RCTs, dental patients in one trial received placebo, nar-
cise diagnosis that matches patients’ perceptions. In un-
cotic analgesics, or narcotic antagonists and those in the
conventional medicine, patient experience is never de-
other trial received only a placebo or a narcotic antago-
valued or brushed aside as unreliable (61). Inevitably,
nist. Dentists knew the possible interventions in both
since the alternative world is not as constrained by the
trials but remained blinded to administration of medi-
dichotomy of objectivity and subjectivity, the chiroprac-
cation. Pain in placebo recipients was significantly worse
tor will find the subluxation, the acupuncturist will de-
in the second trial, in which narcotic drugs were not an
tect the yin–yang disharmony, and the health food ad-
option, than in the first trial (51). An earlier RCT of the
vocate will identify the transgression that makes sense of
effect of physician expectations on hypertension drugs
the patient’s life-world. In addition, if a patient is new
also found that practitioner belief can transform out-
to alternative medicine, an opportunity for exchange is
invariably offered, providing the patient with “theoreti-
Practitioners of unconventional medicine are less re-
cal explanations designed to take the mystery out of
strained by scientific objectivity than practitioners of
process and problems” (62). When it is considered that
conventional medicine. The sensibilities of alternative
40% to 60% of patients may never receive a firm diag-
practitioners are therefore often more optimistic and
nosis in conventional medicine (63, 64), an alternative
positive than those of their mainstream counterparts
diagnosis may be a potent form of nonspecific healing
(53). The characteristics thought to enhance the placebo
that changes the circumstances under which the patient
effect (and any active intervention) seem to be fully op-
exists (65– 67), including reducing the “dysphoria of un-
erational in the offices of alternative medicine.
Besides diagnosis, the healing encounter also estab-
lishes therapeutic goals. Paradoxically, while the alterna-
PATIENT–PRACTITIONER INTERACTION
tive diagnosis tends to be precise, treatment aims can be
The placebo drama is probably more successful if
diverse. Because of such notions as “holistic medicine”
the patient and practitioner find each other’s beliefs and
and “body, mind, spirit,” alternative medicine can have
actions mutually credible or at least intriguing. Recipro-
extremely broad, indeterminate therapeutic targets and
www.annals.org
4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 819
Academia and Clinic The Placebo Effect in Alternative Medicine
therefore, at least from a cultural view, “in some sense
either active or inert ingredients may often yield better re-
cannot fail” (69). Such amorphous goals can provide
sults than an identical treatment that is not as well known
additional maneuvering room for positive progress, or at
(96), and devices or elaborate procedures can have greater
least incremental change (70). If the patient’s symptoms
placebo effects than pills (97, 98). Active placebos (placebos
do not directly improve, it is likely that something pos-
containing medications, such as atropine, that are ineffec-
itive will happen and be attributed to the intervention
tive for the condition being studied but produce recogniz-
(even if the change pertains only to alternative con-
able drug-related side effects) seem to provide genuine
structs, such as the homeopathic spiritual force or the
treatment recognition that leads to heightened placebo ef-
acupuncture qi). Taken together, the alternative diagno-
fects (99, 100). With good showmanship, a well-designed,
sis, prognosis, and treatment aims serve “to regulate
totally inert stage prop can offer this kind of “feedback
symptom intensity and distress” and “create enough cer-
loop” and can produce exaggerated placebo effects.
tainty to diminish the threat of the inchoate while pre-
Two RCTs— one of transcutaneous electrical nerve
serving enough ambiguity to allow for fresh improvisa-
stimulation and one of “placebo electronic machines”—
demonstrated that, with good staging, blank machinescan provide feedback sensations. In the first study, all
patients reported an electrical sensation after adjustment
HE NATURE OF THE ILLNESS
of the dummy apparatus, which was equipped with vi-
The placebo effect may benefit from the types of ill-
sual and sound feedback (101). In the second trial
nesses that alternative medicine commonly treats. Data in-
(which used only dummy machines under two different
dicate that the overwhelming majority of medical condi-
sets of expectations), a significant number of partici-
tions treated by unconventional medicine fall into the
pants “felt” the nonexistent current, and some even vol-
following categories: highly subjective symptoms lacking
unteered that the sensation was “just amazing” (102).
identifiable physiologic correlates, chronic conditions with
Biomedicine and alternative medicine each have a
a fluctuating course often influenced by selective attention,
special allure of mystery and exotic power; it would be
and affective disorders (2, 72). Not surprisingly, these con-
hard to argue that one backdrop consistently provides a
ditions are precisely those that researchers believe are espe-
superior placebo effect. However, alternative medicine
cially susceptible to inordinately strong placebo responses:
has the advantage of always having an intervention sce-
back and chronic pain (73–75), fatigue (76, 77), arthritis
nario. Therapeutic passivity is rarely an option, and
(78, 79) headache (80, 81), allergies (82, 83), hypertension
practitioners can, at a minimum, offer something that is
(in some situations) (84, 85), insomnia (86, 87), asthma
likely to have a placebo effect. In some situations, and at
(13, 88), chronic digestive disorders (89, 90) depression
least for continuous subjective outcomes, an interven-
(91, 92), and anxiety (93). Even researchers who question
tion presumably has a greater effect than no treatment
the existence or significance of a placebo effect—at least in
(94, 103). Also, to demonstrate “active” intervention,
the narrow sense of the outcome produced by a dummy
alternative medicine treatments have unique feedback
intervention— concede its impact when outcomes are con-
loops that are likely to facilitate, if not heighten, sub-
tinuous and subjective (94). Also, persons with self-limiting
stantial placebo responses. For example, chiropractic ad-
diseases, such as the common cold and sprains and strains,
justment often triggers an audible “pop” so that the
also frequently use alternative medicine. In these cases, the
patient can hear the subluxation being fixed (104), acu-
natural course of the disease undoubtedly creates the ap-
puncturists propagate a sensation of vital energy cours-
pearance of treatment response and enhances the percep-
ing through invisible meridians (105), and psychic heal-
tion of unconventional medicine’s effectiveness.
ers summon tingling vibrations (106). TREATMENT AND SETTING
Treatment paraphernalia and setting affect the impact
DOES ALTERNATIVE MEDICINE HAVE ENHANCED
of a placebo performance. For placebo pills, a regimen of
PLACEBO EFFECTS?
four times per day seems more effective than a regimen of
Despite the arguments and speculations already pre-
twice per day (95). A “brand-name” therapy that includes
sented, there is scant empirical evidence that any partic-
820 4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 www.annals.org
The Placebo Effect in Alternative Medicine Academia and Clinic
ular type of alternative medicine used for any particular
alternative medicine would probably require many such
condition has an augmented placebo effect. Even con-
cerning the placebo effect in general, the evidence cited
Some may dismiss these types of investigation as
earlier is often methodologically weak and limited by
useless. After all, a placebo is just a placebo. Others
small numbers and short follow-up periods. Some social
would argue that such avoidance impoverishes and nar-
scientists argue that “for the believer in science, medical
rows the understanding of what patients receive from
care that appears to be scientific would provide a supe-
alternative medicine (and, by extension, conventional
rior placebo; for the believer . . . of whatever other
medicine). Even those who doubt the existence or sig-
cultural system of meaning and values,” alternative med-
nificance of a “narrow” placebo effect seem open to the
icine may “provide a superior placebo” (107). Perhaps
possibility of “broad” placebo effects embedded in the
biomedicine’s effort to eliminate ritual or placebo inter-
psychosocial context of the patient–practitioner relation-
ventions itself produces an improved placebo effect.
Two examples from RCTs may help readers con-
cretely envision an enhanced placebo effect. In a four-arm crossover RCT involving 44 patients with chronic
WHAT IS LEGITIMATE HEALING?
cervical osteoarthritis of more than 6 months’ duration,
Besides clinical and scientific value, the question of
acupuncture, sham acupuncture, and diazepam were all
enhanced placebo effects raises complex ethical ques-
equivalent and were superior to a placebo pill (108). In
tions concerning what is “legitimate” healing. What
this study, the outcome of the ritual of acupuncture
should determine appropriate healing, a patient’s im-
(real and sham acupuncture were not different) equaled
provement from his or her own baseline (clinical signif-
the outcome of an effective drug. In a second RCT,
icance) or relative improvement compared with a pla-
which studied spinal manipulation, 256 patients with
cebo (fastidious efficacy)? As one philosopher of
nonspecific back and neck disorders were randomly as-
medicine has asked, are results less important than
signed to receive manual therapy (the Dutch equivalent
method (3)? Both performative and fastidious efficacy
of chiropractic), physical therapy, placebo-device ther-
can be measured. Which measurement represents uni-
apy with a “detuned” ultrasonography machine and
versal science? Which measurement embodies cultural
“detuned” short-wave diathermy that emitted sounds
judgment on what is “correct” healing? Are the concerns
and lights, or treatment from a general practitioner
of the physician identical to those of the patient? Is
(109). Six weeks of manual therapy and physical therapy
denying patients with nonspecific back pain treatment
were equally and significantly better than the sham ma-
with a sham machine an ethical judgment or a scientific
chine, which significantly outperformed the general
judgment? Should a patient with chronic neck pain who
practitioner. It cannot be determined whether the man-
cannot take diazepam because of unacceptable side ef-
ual and physical therapies had specific treatment effects
fects be denied acupuncture that may have an “en-
or simply yielded better placebo effects than the inani-
hanced placebo effect” because such an effect is “bogus”?
mate gadget. Nonetheless, in this experiment, treatment
with a sham machine surpassed treatment from a com-
Patients’ attitudes toward placebo interventions (es-
petent physician for relief of low back pain.
pecially enhanced interventions) probably differ from
To more rigorously test these possible relative non-
physicians’ attitudes (112). This distinction is probably
specific effects, my colleagues and I are performing a
most evident in surgery, another field in which a height-
National Institutes of Health–funded RCT that ran-
ened placebo effect is possible (97, 113), as illustrated by
domly assigns patients with chronic pain to one of two
two RCTs that tested implantation of fetal dopaminer-
parallel run-in phases. Before entering two subsequent
gic cells for Parkinson disease. Patients with Parkinson
RCTs, one run-in group receives a conventional-appear-
disease seem to have a robust placebo response (114,
ing placebo pill and the other receives an alternative
115); the biochemical substrate of this response in rela-
medicine sham procedure; the main goal of the run-in
tion to the release of dopamine in the striatum has re-
phases is to detect differing placebo effects (97). Any
cently been shown on positron emission tomography
confident assertion about a placebo effect enhanced by
(116). At the conclusion of one of the two RCTs,
www.annals.org
4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 821
Academia and Clinic The Placebo Effect in Alternative Medicine
patients were unblinded, and half were told they had
References
received sham surgery that had performed the same as
1. Temple RJ. When are clinical trials of a given agent vs. placebo no longer
real surgery. In the early reports from this study, both
appropriate or feasible? Control Clin Trials. 1997;18:613-20. [PMID: 9408723] 2. Kaptchuk TJ, Edwards RA, Eisenberg DM. Complementary medicine: effi-
groups experienced significant clinical improvement.
cacy beyond the placebo effect. In: Ernst E, ed. Complementary Medicine:
(The subsequent full report, which included long-term
An Objective Appraisal. Oxford: Butterworth-Heinemann; 1996.
data, reported a less durable placebo effect [117].) When
3. Sullivan MD. Placebo controls and epistemic control in orthodox medicine.
patients who had received the sham surgery were told
J Med Philos. 1993;18:213-31. [PMID: 8315363]
that they could not receive the real but now “discredit-
4. wan Weel C. Examination of context of medicine. Lancet. 2001;357:733-4. [PMID: 11253959]
ed” surgery, as they had been promised in the informed
5. Kaptchuk TJ. Powerful placebo: the dark side of the randomised controlled
consent form, 70% were disappointed or “outraged” be-
trial. Lancet. 1998;351:1722-5. [PMID: 9734904]
cause of the dramatic benefits they had already received
6. Vickers AJ, de Craen AJ. Why use placebos in clinical trials? A narrative review
from sham surgery (118 –120). They wanted the “real”
of the methodological literature. J Clin Epidemiol. 2000;53:157-61. [PMID:10729687]
procedure even if it was equivalent to the sham. Of
7. Feinstein AR. Clinical Epidemiology. Philadelphia: WB Saunders; 1985.
interest, the second RCT, which also found no differ-
8. Tambiah SJ. Magic, Science, Religion, and the Scope of Rationality. Cam-
ence between active and imitation surgery, demon-
bridge, United Kingdom: Cambridge Univ Pr; 1990.
strated a stable and significant placebo effect after 18
9. Shapiro AK, Shapiro E. The Powerful Placebo: From Ancient Priest to Mod-
months (121). For many patients, performative efficacy
ern Physician. Baltimore: Johns Hopkins Univ Pr; 1997.
may be more critical than fastidious efficacy. Obviously,
10. Wolf S, Doering CR, Clark ML, Hagans JA. Chance distribution and the placebo “reactor.” J Lab Clin Med. 1957;49:837-41.
this illustration is not meant to advocate ritualistic sur-
11. Liberman RP. The elusive placebo reactor. Neuropsychopharmacology.
gery. Rather, it is meant to highlight the complex rela-
tionship among clinical, scientific, and ethical judg-
12. Luparello TJ, Leist N, Lourie CH, Sweet P. The interaction of psychologic
stimuli and pharmacologic agents on airway reactivity in asthmatic subjects. Psychosom Med. 1970;32:509-13. [PMID: 4097491] 13. Butler C, Steptoe A. Placebo responses: an experimental study of psycho-
physiological processes in asthmatic volunteers. Br J Clin Psychol. 1986;25(Pt
ONCLUSION
Alternative medicine may be composed of healing
14. Sodergren SC, Hyland ME. Expectancy and asthma. In: Kirsch I, ed. How
rituals that have especially potent performative efficacy.
Expectancies Shape Experience. Washington, DC: American Psychological Assoc;
Therapeutic characteristics that may enhance placebo ef-
1999. 15. Sternbach RA. The effects of instructional sets on autonomic responsivity.
fects seem especially prominent in unconventional heal-
ing. Although more research into this question is neces-
16. Kaptchuk TJ. The double-blind, randomized, placebo-controlled trial. Gold
sary before any such assertion can be made with
standard or golden calf? J Clin Epidemiol. 2001;54:541-9. [PMID: 11377113]
confidence, an enhanced placebo effect raises complex
17. Mitchell SH, Laurent CL, de Wit H. Interaction of expectancy and the
questions about what is legitimate therapy, and who de-
pharmacological effects of d-amphetamine: subjective effects and self-administra-tion. Psychopharmacology (Berl). 1996;125:371-8. [PMID: 8826542]
18. Flaten MG, Simonsen T, Olsen H. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom Med.
From Harvard Medical School, Boston, Massachusetts.
1999;61:250-5. [PMID: 10204979] 19. Dworkin SF, Chen AC, Schubert MM, Clark DW. Cognitive modification Acknowledgment: The author thanks Robb Scholten, June Cobb, Pat
of pain: information with N2O. Pain. 1984;19:339-51. [PMID: 6483450]
Wilkinson, John C. Wilson, Maria Van Rompay, and Marcia Rich for
20. Horwitz RI, Horwitz SM. Adherence to treatment and health outcomes.
Arch Intern Med. 1993;153:1863-8. [PMID: 8250647] 21. Czajkowski SM, Chesney MA. Adherence and the placebo effect. In: Shu- maker SA, Schron EB, Ockene JK, eds. The Handbook of Health Behavior Grant Support: In part by the National Institutes of Health
(1R01AT00402-01, U24 AR43441, and 1R21AT00553), the John E.
22. Influence of adherence to treatment and response of cholesterol on mortality
Fetzer Institute, the Waletzky Charitable Trust, the Friends of Beth
in the coronary drug project. N Engl J Med. 1980;303:1038-41. [PMID:
Israel Deaconess Medical Center, and American Specialty Health Plan.
6999345] 23. Horwitz RI, Viscoli CM, Berkman L, Donaldson RM, Horwitz SM, Requests for Single Reprints: Ted J. Kaptchuk, OMD, Beth Israel Murray CJ, et al. Treatment adherence and risk of death after a myocardial
Deaconess Medical Center, Harvard Medical School, 330 Brookline Av-
infarction. Lancet. 1990;336:542-5. [PMID: 1975045]
24. Gallagher EJ, Viscoli CM, Horwitz RI. The relationship of treatment 822 4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 www.annals.org
The Placebo Effect in Alternative Medicine Academia and Clinic
adherence to the risk of death after myocardial infarction in women. JAMA.
sic effect of tramadol in chronic pain patients: a 2 ϫ 2 factorial, randomised,
placebo-controlled, double-blind trial. In: Placebos and Placebo Effects in Clini-
25. Mattocks KM, Horwitz RI. Placebos, active control groups, and the unpre-
cal Trials [Dissertation]. Amsterdam: Univ of Amsterdam; 1998.
dictability paradox. Biol Psychiatry. 2000;47:693-8. [PMID: 10773175]
47. Cooper WD, Currie WJ, Vandenburg MJ. The influence of physicians’
26. Wennberg JE. What is outcomes research? In: Gelijns AC, ed. Modern
instructions on the outcome of antihypertensive therapy. Br J Clin Pract. 1983;
Methods of Clinical Investigation. Washington, DC: National Academy Pr;
48. Kincheloe JE, Mealiea WL Jr, Mattison GD, Seib K. Psychophysical mea-
27. McPherson K, Britton AR, Wennberg JE. Are randomized controlled trials
surement on pain perception after administration of a topical anesthetic. Quin-
controlled? Patient preferences and unblind trials. J R Soc Med. 1997;90:652-6.
tessence Int. 1991;22:311-5. [PMID: 1891606]
49. Crow R, Gage H, Hampson S, Hart J, Kimber A, Thomas H. The role of
28. Brewin CR, Bradley C. Patient preferences and randomised clinical trials.
expectancies in the placebo effect and their use in the delivery of health care: a
systematic review. Health Technol Assess. 1999;3:1-96. [PMID: 10448203]
29. Kaptchuk TJ. History of vitalism. In: Micozzi MS, ed. Fundamentals of
50. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of
Complementary and Alternative Medicine. New York: Churchill Livingstone;
context effects on health outcomes: a systematic review. Lancet. 2001;357:757-
30. Kirmayer LJ. Healing and the invention of metaphor: the effectiveness of
51. Gracely RH, Dubner R, Deeter WR, Wolskee PJ. Clinicians’ expectations
symbols revisited. Cult Med Psychiatry. 1993;17:161-95. [PMID: 7693395]
influence placebo analgesia [Letter]. Lancet. 1985;1:43. [PMID: 2856960]
31. Zollman C, Vickers A. ABC of complementary medicine. Complementary
52. Shapiro AP, Myer T, Reiser MF, Ferris EB. Comparison of blood pressure
medicine and the patient. BMJ. 1999;319:1486-9. [PMID: 10582937]
response to Veriloid and to the doctor. Psychosom Med. 1954;16:478-88.
32. Shapiro AK. Iatroplacebogenics. International Pharmacopsychiatry. 1969;2:
53. Kaptchuk TJ, Eisenberg DM. The persuasive appeal of alternative medicine.
Ann Intern Med. 1998;129:1061-5. [PMID: 9867762]
33. Gryll SL, Katahn M. Situational factors contributing to the placebos effect.
54. Stewart MA. Effective physician-patient communication and health out-
Psychopharmacology (Berl). 1978;57:253-61. [PMID: 97705] .
comes: a review. CMAJ. 1995;152:1423-33. [PMID: 7728691]
34. Hashish I, Hai HK, Harvey W, Feinmann C, Harris M. Reduction of
55. Ong LM, de Haes JC, Hoos AM, Lammes FB. Doctor-patient communi-
postoperative pain and swelling by ultrasound treatment: a placebo effect. Pain.
cation: a review of the literature. Soc Sci Med. 1995;40:903-18. [PMID:
35. Ho KH, Hashish I, Salmon P, Freeman R, Harvey W. Reduction of post-
56. Kaplan SH, Greenfield S, Ware JE Jr. Assessing the effects of physician-
operative swelling by a placebo effect. J Psychosom Res. 1988;32:197-205.
patient interactions on the outcomes of chronic disease. Med Care. 1989;27:
36. Bergmann JF, Chassany O, Gandiol J, Deblois P, Kanis JA, Segrestaa JM,
57. Finkler K, Correa M. Factors influencing patient perceived recovery in Mex- et al. A randomised clinical trial of the effect of informed consent on the analgesic
ico. Soc Sci Med. 1996;42:199-207. [PMID: 8928029]
activity of placebo and naproxen in cancer pain. Clin Trials Metaanal. 1994;29:
58. Bass MJ, Buck C, Turner L, Dickie G, Pratt G, Robinson HC. The
physician’s actions and the outcome of illness in family practice. J Fam Pract.
37. Uhlenhuth EH, Rickels K, Fisher S, Park LC, Lipman RS, Mock J. Drug,
doctor’s verbal attitude and clinic setting in the symptomatic response to phar-
59. Thomas KB. General practice consultations: is there any point in being
macotherapy. Psychopharmacologia. 1966;9:392-418. [PMID: 4872909]
positive? Br Med J (Clin Res Ed). 1987;294:1200-2. [PMID: 3109581]
38. Fisher S, Cole JO, Rickels K, Uhlenhuth EH. Drug-set interaction: the
60. Olsson B, Olsson B, Tibblin G. Effect of patients’ expectations on recovery
effect of expectations on drug response in outpatients. Neuropsychopharmacol-
from acute tonsillitis. Fam Pract. 1989;6:188-92. [PMID: 2792618]
61. Hahn RA. “Treat the patient, not the lab:” internal medicine and the concept
39. Wheatley D. Influence of doctors’ and patients’ attitudes in the treatment of
of ‘person’. Cult Med Psychiatry. 1982;6:219-36. [PMID: 7172711]
neurotic illness. Lancet. 1967;2:1133-5. [PMID: 4168567]
62. Oths K. Communication in a chiropractic clinic: how a D.C. treats his
40. Rabkin JG, McGrath PJ, Quitkin FM, Tricamo E, Stewart JW, Klein DF.
patients. Cult Med Psychiatry. 1994;18:83-113. [PMID: 8082319]
Effects of pill-giving on maintenance of placebo response in patients with chronic
63. Thomas KB. The placebo in general practice. Lancet. 1994;344:1066-7.
mild depression. Am J Psychiatry. 1990;147:1622-6. [PMID: 2244639]
41. Affleck DC, Eaton MT, Mansfield E. The action of a medication and the
64. Adler HM, Hammett VB. The doctor-patient relationship revisited. An
physician’s expectations. Nebr State Med J. 1966;51:331-4. [PMID: 4227004]
analysis of the placebo effect. Ann Intern Med. 1973;78:595-8. [PMID:
42. Agras WS, Horne M, Taylor CB. Expectation and the blood-pressure-
lowering effects of relaxation. Psychosom Med. 1982;44:389-95. [PMID: 6755527]
65. Sox HC Jr, Margulies I, Sox CH. Psychologically mediated effects of diag-
43. Amigo I, Cuesta V, Ferna´ndez A, Gonza´lez A. The effect of verbal instruc-
nostic tests. Ann Intern Med. 1981;95:680-5. [PMID: 7305144]
tions on blood pressure measurement. J Hypertens. 1993;11:293-6. [PMID:
66. Adler HM. The history of the present illness as treatment: who’s listening,
and why does it matter? J Am Board Fam Pract. 1997;10:28-35. [PMID:
44. Freund J, Krupp G, Goodenough D, Preston LW. The doctor-patient
relationship and drug effect. Clin Pharmacol Ther. 1972;13:172-80. [PMID:
67. Brody H, Waters DB. Diagnosis is treatment. J Fam Pract. 1980;10:445-9.
45. Wied GI. U
¨ ber die Bedeutung der Suggestion in der Therapie klimak-
68. Novack DH. Therapeutic aspects of the clinical encounter. J Gen Intern
terischer Ausfallerscheinungen. Arztliche Wochenschrift. 1953;8:623-5.
46. de Craen AJM. Impact of experimentally induced expectancy on the analge-
69. Csordas TJ. The rhetoric of transformation in ritual healing. Cult Med www.annals.org
4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 823
Academia and Clinic The Placebo Effect in Alternative Medicine
Psychiatry. 1983;7:333-75. [PMID: 6661923]
cation of the placebo response in ulcerative colitis. Gastroenterology. 1997;112:
70. Csordas TJ. Elements of charismatic persuasion and healing. Med Anthropol
91. Brown WA, Johnson MF, Chen MG. Clinical features of depressed patients
71. Kirmayer LJ. Improvisation and authority in illness meaning. Cult Med
who do and do not improve with placebo. Psychiatry Res. 1992;41:203-14.
Psychiatry. 1994;18:183-214. [PMID: 7924400]
72. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M,
92. Kirsch I, Sapirstein G. Listening to Prozac but hearing placebo: a meta- et al. Trends in alternative medicine use in the United States, 1990-1997: results
analysis of antidepressant medications. In: Kirsch I, ed. How Expectancies Shape
of a follow-up national survey. JAMA. 1998;280:1569-75. [PMID: 9820257]
Experience. Washington, DC: American Psychological Assoc; 1999.
73. Turner JA, Deyo RA, Loeser JD, Von Korff M, Fordyce WE. The impor-
93. Rosenberg NK, Mellergård M, Rosenberg R, Beck P, Ottosson JO. Char-
tance of placebo effects in pain treatment and research. JAMA. 1994;271:1609-
acteristics of panic disorder patients responding to placebo. Acta Psychiatr Scand
74. Wall PD. Pain and the placebo response. In: Bock G, Marsh J, eds. Exper-
94. Hro´bjartsson A, Gøtzsche PC. Is the placebo powerless? An analysis of
imental and Theoretical Studies of Consciousness. Ciba Foundation Symposium
clinical trials comparing placebo with no treatment. N Engl J Med. 2001;344:
75. McQuay H, Carroll D, Moore A. Variation in the placebo effect in random-
95. de Craen AJ, Moerman DE, Heisterkamp SH, Tytgat GN, Tijssen JG,
ised controlled trials of analgesics: all is as blind as it seems. Pain. 1996;64:331-5. Kleijnen J. Placebo effect in the treatment of duodenal ulcer. Br J Clin Pharma-
76. Lasagna L, Laties VG, Dohan JL. Further studies on the “pharmacology” of
96. Branthwaite A, Cooper P. Analgesic effects of branding in treatment of
placebo administration. J Clin Invest. 1958;37:533-7.
headaches. Br Med J (Clin Res Ed). 1981;282:1576-8. [PMID: 6786566]
77. Brodeur DW. The effects of stimulant and tranquilizer placebos on healthy
97. Kaptchuk TJ, Goldman P, Stone DA, Stason WB. Do medical devices have
subjects in a real-life situation. Psychopharmacologia. 1965;7:444-52. [PMID:
enhanced placebo effects? J Clin Epidemiol. 2000;53:786-92. [PMID:
78. Morison RA, Woodmansey A, Young AJ. Placebo responses in an arthritis
98. de Craen AJ, Tijssen JG, de Gans J, Kleijnen J. Placebo effect in the acute
trial. Ann Rheum Dis. 1961;20:178-85.
treatment of migraine: subcutaneous placebos are better than oral placebos.
79. Pillemer SR, Fowler SE, Tilley BC, Alarco´n GS, Heyse SP, Trentham DE,
J Neurol. 2000;247:183-8. [PMID: 10787112]
et al . Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial.
99. Moncrieff J, Wessely S, Hardy R. Meta-analysis of trials comparing antide-
MIRA Trial Group. Minocycline in Rheumatoid Arthritis. Arthritis Rheum.
pressants with active placebos. Br J Psychiatry. 1998;172:227-31. [PMID:
80. Couch JR Jr. Placebo effect and clinical trials in migraine therapy. Neuroepi-
100. Fisher S, Greenberg RP. How sound is the double-blind design for evalu-
demiology. 1987;6:178-85. [PMID: 3317098]
ating psychotropic drugs? J Nerv Ment Dis. 1993;181:345-50. [PMID:
81. Diener HC, Dowson AJ, Ferrari M, Nappi G, Tfelt-Hansen P. Unbalanced
randomization influences placebo response: scientific versus ethical issues around
101. Marchand S, Charest J, Li J, Chenard JR, Lavignolle B, Laurencelle L. Is
the use of placebo in migraine trials. Cephalalgia. 1999;19:699-700. [PMID:
TENS purely a placebo effect? A controlled study on chronic low back pain. Pain.
82. Kagan G, Dabrowicki E, Huddlestone L, Kapur TR, Wolstencroft P. A
102. Schwitzgebel RK, Traugott M. Initial note on the placebo effect of ma-
double blind trial of terfenadine and placebo in hay fever using a substitution
chines. Behav Sci. 1968;13:267-73. [PMID: 5663895]
technique for non-responders. J Int Med Res. 1980;8:404-7. [PMID: 6108264]
103. Ernst E, Resch KL. Concept of true and perceived placebo effects. BMJ.
83. D’Souza MF, Emanuel MB, Gregg J, Charlton J, Goldschmidt J. A method
for evaluating therapy for hay fever. A comparison of four treatments. Clin Al-
104. Kaptchuk TJ, Eisenberg DM. Chiropractic: origins, controversies, and
contributions. Arch Intern Med. 1998;158:2215-24. [PMID: 9818801]
84. Preston RA, Materson BJ, Reda DJ, Williams DW. Placebo-associated
105. Kaptchuk TJ. The Web That Has No Weaver: Understanding Chinese
blood pressure response and adverse effects in the treatment of hypertension:
Medicine. Chicago: Contemporary; 2000.
observations from a Department of Veterans Affairs Cooperative Study. Arch
106. McGuire MB. Ritual Healing in Suburban America. New Brunswick, NJ:
Intern Med. 2000;160:1449-54. [PMID: 10826457]
85. Suchman AL, Ader R. Classic conditioning and placebo effects in crossover
107. Riley JN. Western medicine’s attempt to become more scientific: examples
studies. Clin Pharmacol Ther. 1992;52:372-7. [PMID: 1424409]
from the United States and Thailand [1]. Soc Sci Med. 1977;11:549-60. [PMID:
86. Storms MD, Nisbett RE. Insomnia and the attribution process. J Pers Soc
108. Thomas M, Eriksson SV, Lundeberg T. A comparative study of diazepam
87. Bootzin RR, Herman CP, Nicassio P. The power of suggestion: another
and acupuncture in patients with osteoarthritis pain: a placebo controlled study.
examination of misattribution and insomnia. J Pers Soc Psychol. 1976;34:673-9.
Am J Chin Med. 1991;19:95-100. [PMID: 1816730]
109. Koes BW, Bouter LM, van Mameren H, Essers AH, Verstegen GM,
88. Godfrey S, Silverman M. Demonstration by placebo response in asthma by Hofhuizen DM, et al. The effectiveness of manual therapy, physiotherapy, and
means of exercise testing. J Psychosom Res. 1973;17:293-7. [PMID: 4206466]
treatment by the general practitioner for nonspecific back and neck complaints.
89. Moerman DE. Cultural variations in the placebo effect: ulcers, anxiety, and
A randomized clinical trial. Spine. 1992;17:28-35. [PMID: 1531552]
blood pressure. Med Anthropol Q. 2000;14:51-72. [PMID: 10812563]
110. Hro´bjartsson A, Gøtzsche PC. Is the placebo powerless? [Letter] N Engl
90. Ilnyckyj A, Shanahan F, Anton PA, Cheang M, Bernstein CN. Quantifi- 824 4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 www.annals.org
The Placebo Effect in Alternative Medicine Academia and Clinic
111. Hro´bjartsson A, Gøtzsche PC. Core belief in powerful effects of placebo
Parkinson’s disease. Science. 2001;293:1164-6. [PMID: 11498597]
interventions is in conflict with no evidence of important effects in a large sys-
117. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, et al.
tematic review. Advances in Mind-Body Medicine. 2001;17:312-8.
Transplantation of embryonic dopamine neurons for severe Parkinson’s disease.
112. Lyno¨e N, Mattsson B, Sandlund M. The attitudes of patients and physi-
N Engl J Med. 2001;344:710-9. [PMID: 11236774]
cians towards placebo treatment—a comparative study. Soc Sci Med. 1993;36:
118. Husten L. Fetal-cell-implantation trial yields mixed results. Lancet. 1999;
113. Johnson AG. Surgery as a placebo. Lancet. 1994;344:1140-2. [PMID:
119. Macklin R. The ethical problems with sham surgery in clinical research.
N Engl J Med. 1999;341:992-6. [PMID: 10498498]
114. Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D. The placebo
120. Johannes L. Sham surgery is used to test effectiveness of novel operations.
response in Parkinson’s disease. Parkinson Study Group. Clin Neuropharmacol.
Wall Street Journal. 1998;11 December:A1, A8.
121. Watts RL, Freeman RA, Hauser RA, Bakay SA, Ellias AJ, Stoessl AJ, et al.
115. Goetz CG, Leurgans S, Raman R, Stebbins GT. Objective changes in
A double-blind, randomized, controlled, multicenter clinical trial of the safety
motor function during placebo treatment in PD. Neurology. 2000;54:710-4.
and efficacy of stereotaxic intrastriatal implantation of fetal porcine ventral mes-
encephalic tissue (NeurocellTM-PD) vs. imitation surgery in patients with Parkin-
116. de la Fuente-Ferna´ndez R, Ruth TJ, Sossi V, Schulzer M, Calne DB,
son’s disease (PD) [Abstract]. Parkinsonism and Related Disorders. 2001;7
Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in
Sometimes we no longer know what is true for us, in which direction our ownintegrity lies . . . Reclaiming ourselves usually means coming to recognize and acceptthat 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 canceleach other out but offer us a full range of power and response to life. Life is ascomplex as we are.
One of the blessings of growing older is the discovery that many of the things I oncebelieved 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 endto be among my shortcomings . . . What a blessing it is to outlive yourself-judgments and harvest your failures.
Rachel Naomi Remen, MDKitchen Table Wisdom: Stories That HealNew York: Riverhead Books; 1996:35-8
Submitted by:George Ho Jr., MDEast Carolina University School of MedicineGreenville, NC 27858
Submissions from readers are welcomed. If the quotation is published, the sender’s name will beacknowledged. Please include a complete citation (along with page number on which the quotation wasfound), as done for any reference.–The Editorwww.annals.org
4 June 2002 Annals of Internal Medicine Volume 136 • Number 11 825
The Break-up of the Ksar: Settlement Change and Common Property Institutions on the Saharan Frontier Draft Paper Not For Citation The IASCP Conference ABSTRACT In spite of the French colonial intrusion, up to 1950s, resource management in Saharan villages constituted what some have called the syndrome of collectivity. The syndrome of collectivity was the product of three i
Mobbing gegen Christoph Mörgeli am Medizinhisto- rischen Institut und Museum Gegen Christoph Mörgeli wurde speziell seit Februar 2010 und damit seit der Direktionsstellvertretung durch Iris Ritzmann und verstärkt seit Februar 2011 anlässlich der Direktionsübernahme von Flurin Condrau ein intensives Mob- bing betrieben. Die im folgenden nachgewiesenen systematischen, feindseli- gen und v