Annals of Internal Medicine 2002 (Jun 4); 136 (11): 817–825 ~ FULL TEXT
Ted J. Kaptchuk, OMD
Harvard Medical School,
Boston, Massachusetts, USA.
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, patient-practitioner 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?
From the FULL TEXT Article:
Efficacious 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). [1–3] 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 patient’s 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.  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. 
Given the privileged status of specific effects, it is
not surprising that the clinical impact of alternative
medicine’s placebo effects are routinely ignored.  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 alternative
medicine and raises the possibility that some
types of unconventional medicine may produce placebo
outcomes that are dramatic and, from the patient’s 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 patient–practitioner relationship,
including attention; communication of concern; intense
monitoring; diagnostic procedures; labeling of complaint;
and alterations produced in a patient’s expectancy,
anxiety, and relationship to the illness.
asks whether alternative medicine can have an “enhanced”
placebo effect. In some conditions, can any of
alternative medicine’s 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”.  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” , alternative medicine
may administer an especially large dose of what anthropologists
call “performative efficacy”.  Performative
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, patient–practitioner interaction,
nature of the illness, and treatment and setting —
and examines their “placebogenic” potentials in unconventional
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.
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. [12–14] 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.  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 patient’s 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
with taking placebo and those who do not — are associated
not only with symptom relief but also with concrete
end points, including survival. [22–24] Indeed,
differences in adherence are associated with differences
in outcomes that exceed the effects of many pharmaceutical
agents.  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
In contrast to conventional medicine, with its measured
objectivity, alternative medicine offers a charged
constellation of expectations. Alternative medicine’s 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.  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”. 
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.  In this situation,
patients’ hope (based on no previous experience
with alternative medicine) may provide an opportunity
for “deconditioning” from previous unsuccessful medical
The practitioner-healer must expertly play the role
of heroic rescuer to facilitate a placebo effect.  Numerous
RCTs have compared optimistic or enthusiastic
physician attitudes toward drug or placebo with neutral
or doubtful physician attitudes. Practitioners have had
significant impact on such clinical conditions as pain [36–36], psychiatric illness [37–41], hypertension [42, 43], obesity , and perimenopause symptoms. 
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”.  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”. 
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.  An earlier RCT of the
effect of physician expectations on hypertension drugs
also found that practitioner belief can transform outcomes. 
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.  The characteristics thought to enhance the placebo
effect (and any active intervention) seem to be fully operational
in the offices of alternative medicine.
The placebo drama is probably more successful if
the patient and practitioner find each other’s beliefs and
actions mutually credible or at least intriguing. Reciprocal
expectations need to be negotiated and joined in the
patient–physician duet. Many studies indicate that the
patient–practitioner encounter is a potent factor in
health outcomes [54–56] and that for many non–lifethreatening
illnesses, clear diagnosis, assurance of recovery,
opportunity for dialogue, and physician–patient
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 2X2 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.  A similar experiment in 100
patients with acute tonsillitis had analogous results. 
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.  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 yin–yang disharmony, and the health food advocate
will identify the transgression that makes sense of
the patient’s 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”.  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”. 
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
therefore, at least from a cultural view, “in some sense
cannot fail”.  Such amorphous goals can provide
additional maneuvering room for positive progress, or at
least incremental change.  If the patient’s 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”. 
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 [73–75],
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
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.  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 medicine’s 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.  A “brand-name” therapy that includes
either active or inert ingredients may often yield better results
than an identical treatment that is not as well known , 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.  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”. 
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 , acupuncturists
propagate a sensation of vital energy coursing
through invisible meridians , and psychic healers
summon tingling vibrations. 
DOES ALTERNATIVE MEDICINE HAVE ENHANCED PLACEBO EFFECTS?
Despite the arguments and speculations already presented,
there is scant empirical evidence that any particular 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”.  Perhaps
biomedicine’s 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.  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.  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 Health–funded 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.  Any
confident assertion about a placebo effect enhanced by
alternative medicine would probably require many such
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 patient–practitioner 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 patient’s 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?  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.  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.  At the conclusion of one of the two RCTs,
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. ) 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.  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.
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.
The author thanks Robb Scholten, June Cobb, Pat
Wilkinson, John C. Wilson, Maria Van Rompay, and Marcia Rich for
editorial and research assistance.
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.
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