An exploration of the relationship between placebo and ... · the brain’s ‘‘inner...
Transcript of An exploration of the relationship between placebo and ... · the brain’s ‘‘inner...
CLINICAL REVIEW
An exploration of the relationship
between placebo and
homeopathy and the implications
for clinical trial design
Claire Haresnape
Barts and the London School of Medicine and Dentistry, Queen Mary University of London, William Harvey Research
Institute, London, EC1M 6BQ, UK
Correspondence to: Claire Haresnape. Email: [email protected]
Summary
Placebo appears to be a real neurobiological phenomenon that has
evolved through the selection pressure to be able to heal ourselves.
The complex language and social structures of humans means that we can
attribute meaning to therapeutic encounters with culturally sanctioned
authority figures and we can use our attachment to such figures to gen-
erate hope for recovery. Different mechanisms may be involved in the
neurobiological aspect of placebo including anxiety, learning, condition-
ing as well as individual genetic variation. Examination of the published
work shows that while some trials do seem to indicate a specific mode of
action for homeopathic remedies other trials do not and this is an issue
that needs to be addressed at the trial design stage. A clinical trial that
includes both a placebo group and a non-participating control arm is the
most powerful design for separating the non-specific and polymorphic
placebo effect from the specific effects of trial medication. The control
variables in a trial of homeopathic medication should also include the
process of consultation as this may assume a meaning for the individual
that can also be associated with a placebo effect.
Introduction
It is a commonly held belief that homeopathy is
‘nothing more’ than a placebo effect, a turn of
phrase which seems to dismiss as ineffective both
homeopathy and the role of the placebo in healing.The aim of this short report is to explore the
relationship between homeopathy and placebo,
how these are connected to self-healing and how
we can design a clinical trial to measure these
interconnected effects.
Recent insights into the changes associated
with placebo may explain why the placebo
response trait could be positively selected for
during our evolutionary history:
‘It is becoming ever more apparent that ‘the
placebo effect’ is polymorphic in both its trig-
ger and its expression, and that the mechan-
isms for placebo responses within the body are
diverse. It is also clear that in all societies heal-
ing modalities have developed to maximize
DECLARATIONS
Competing interests
This article has
been funded by a
grant from
Biological Heilmittel
Heel GmbH and the
author has worked
on a consultancy
basis for BioPathica
Ltd, Ashford, Kent
Funding
This work was sup-
ported by an educa-
tional grant from
Biologische
Heilmittel Heel
GmbH,
Dr.-Reckeweg-Str.
2-4,76532 Baden-
Baden, Deutschland
Ethical approval
Not applicable
Guarantor
CH
Contributorship
Sole authorship
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 1
the placebo response in an attempt to over-
come assaults to well being. This raises the
question as to whether the placebo response,
like other self-healing mechanisms, may be an
evolutionary adaptation.’1
Given the extreme plasticity of the human brain in
response to experience and the potential differences
due to genetic variation, it is clear that the old
‘nature vs. nurture’ debate has some relevance to
our understanding of placebo. If the range of indi-
vidual placebo responses is wide then this also has
implications for the large sample sizes needed for
meaningful analysis of clinical trial data.
Methods
The evidence for this review was gathered from a
search of the PubMed database (http://www.
ncbi.nlm.nih.gov/pubmed), using the terms
‘homeopathy’, ‘self-healing’ and ‘placebo’, which
yielded 19 published papers.In order to review the trial design of published
trials of homeopathy with a non-treatment group,
a PubMed search was conducted using the search
terms ‘homeopathy’ and ‘clinical trials’ with the
filter ‘last five years’ and excluding surveys with
no placebo, animals and plant studies. This gen-
erated 41 papers for analysis.
In order to find material about trials that showa specific effect for homeopathy, a PubMed search
using the terms ‘homeopathy’þ ‘specific’ and fil-
tered to show clinical trials over the last five years
in human subject returned only 10 studies.
Additional inspiration and material was
sourced at the inaugural meeting of the Pain
Medicine Section of the Royal Society of
Medicine ‘The role of the placebo in clinical care’which was held on Friday 18 November 2011.
Professor Atholl Johnston provided the link to
the data on the discovery of the genetic basis for
the placebo effect in IBS patients. The information
about homeopathy was cited using books from
the author’s own library and details are included
in the bibliography.
Genetic individuality
The individual nature of each patient’s response
has some basis in genetic variation and this is
identified as a fruitful new avenue of research
by Benedetti and Amanzio.2 In a recent study
from Beth Israel Deaconess Medical Centre
(BIDMC) and Harvard Medical School (HMS), sci-
entists claim to have identified genetic differences
between people who respond to placebos during
trials and those who do not.3
Placebo, semiotics andmeaning
Medical or therapeutic treatment happens to
unique individuals, each with their own interpret-
ation of the experience. Walach4 recognizes that
the individual psychological and psychosomaticreceptive action on the part of the patient is rele-
vant to therapeutic success.
Meissner et al.5 confirms that the placebo effect
is ‘a real neurobiological phenomenon and that
the brain’s ‘‘inner pharmacy’’ is a critical deter-
minant for the occurrence of psychobiological
and behavioral changes relevant to healing pro-
cesses and wellbeing’.Meissner6 proposes that verbal suggestions
during placebo interventions may activate associ-
ation networks in the brain that store memories of
the appropriate autonomic response. Organ func-
tions regulated by the Autonomic Nervous
System (ANS) including the cardiovascular,
gastrointestinal and pulmonary systems are
amenable to both placebo and nocebointerventions.
Benedetti and how placeboschange the patient’s brain
The 2011 review of neurobiological findings by
Benedetti et al.7 provides a compelling view of
placebo as a psychosocial context effect wheresocial stimuli such as words and rituals of the
therapeutic act may change the chemistry and cir-
cuitry of the patient’s brain. Benedetti et al. show
that drugs are administered into a complex bio-
chemical environment that varies according to the
patient’s cognitive/affective state and previous
exposure to other pharmacological agents. The
mechanisms activated by placebo are the sameas those activated by drugs, which suggests a cog-
nitive/affective interference with drug actions.
Rather than one common mechanism of action,
they suggest that there is a whole ‘melting pot’ of
different placebo effects operate at different times
Acknowledgements
The author would
like to acknowledge
the help of Prof
Atholl Johnston, Dr
Art Tucker, Dr Carol
Rivas, Mrs Virginia
Shankland, Dr Len
Parkyn, Neil
MacLachlan, Dr Neil
Elnaggar, Sister
Michelle Thomas,
Mr and Mrs Roger
Wilson and Dr
Istvan Zatik
Provenance
Submitted; peer
reviewed by
Heather Goodare
Journal of the Royal Society of Medicine Short Reports
2 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
and under different circumstances. Sometimes
anxiety is modulated, at other times reward mech-
anisms are involved and in other circumstances
different types of learning, conditioning or even
genetic variants may play a role in placebo
responsiveness.
Placebo in relation to evolution
The role of expectation of benefit and the hope of
healing have also been examined by Benedetti and
Amanzio.2 The expectation of future events is
known to modulate anxiety and to induce physio-
logical changes through reward mechanisms. Thenocebo effect, which is the opposite of the placebo
effect, provides some of the best evidence of the
role that anxiety plays in placebo responses.
There is a survival value to the ability to pre-
pare the body to anticipate and cope with a future
event. The main purpose of perception is to help
predict the future,8 if expectations about the
future change the body’s defensive emotional,behavioural and physiological responses then pla-
cebo responsiveness could be seen as a trait
favoured by natural selection.
From the evolutionary perspective individuals
who can protect themselves, heal themselves and
recuperate from infections, injury and illness are
more likely to survive and reproduce and there-
fore pass these adaptive traits on to theiroffspring.
The connection betweenillness and disease
One of the themes of this approach is the distinc-
tion between disease and illness. Disease may be
considered to be patho-physiological whereas ill-ness is phenomenological. Illness is the lived
experience (emotions) of detriment to health
including the symptomatic manifestation of dis-
ease. Miller et al.9 suggest that the placebo effect
operates predominantly by producing symptom-
atic relief of illness rather than modifying the
physiology of disease.
The role of the ‘healer’ inplacebo
Because the symptoms of illness have themselves
a survival value, it is reasonable to suppose that it
will only be ‘safe’ to ‘turn them off’ when sanc-
tioned by a ‘healer’ or practitioner.
‘From a psychodynamic perspective the hea-
ler’s authority and ability to comfort may be
a projection of parental care, operating by a
process of transference.’10
Ernst and Resch11 have noted that procedures
intimately involving the patient as well as those
that are invasive, like acupuncture or ultrasound
are associated with a more powerful true placebo
effect than oral drug treatment. In these situations
the ‘healer’ is playing an immediate and activerole and the ‘patient’ is interpreting this as some-
how more powerful, direct and significant.
The context of the clinical encounter and the
relationship between the healer and the patient
are imbued with meaning and enshrined in
ritual. Dr Cecil Helman12 relates how his consult-
ing room is a type of stage-set where small human
dramas are played out every day. ‘Props, cos-tumes, sets and a precise choreography’ achieve
the creation of a ‘certain atmosphere of belief and
expectation’.
Self-healing and homeopathy
‘We are inclined to attribute recovery from dis-
ease to the ministrations of healers when, in
point of fact, it is often due to self-limiting dis-
eases and the automatic natural healing of the
organism.’9
It is important to distinguish interpersonal heal-
ing from two other forms of healing, natural healing
and technological healing, because homeopathy is
often described as ‘natural’ and perceived as analternative to ‘technological’ healing options:
‘Natural healing is the spontaneous or automatic
response of the body to disease or injury, exem-
plified by internal mechanisms of fighting infec-
tion and wound healing. Technological healing
consists of the full array of medical and surgical
treatment that have pharmacological or physio-
logical properties capable of promoting cure,
disease control, or symptomatic relief.’9
The homeopathic consultation process is a two-
way process in which the patient narrative
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 3
is received by the therapist and generates ques-
tions or reflections. This must involve a psycho-
logical transaction between patient and therapist
that will be perceived through the frame of their
previous experiences. The patient is conscious,
active and ‘being heard’.Benedetti has explored the role of the pre-
frontal cortex in placebo responses and concluded
that if prefrontal functioning is impaired, placebo
responses are reduced or totally lacking, as occurs
in dementia of the Alzheimer’s type.7
The homeopathic clinical encounter will
involve healing on many levels as there will be
interpersonal transactions including psycho-dynamic effects, the ritual associated with con-
sultation and perhaps lifestyle advice and
education. The patients may also be receiving con-
current technological healing from their medical
practitioners as well as being prescribed a homeo-
pathic preparation to aid ‘natural healing’.
The philosophy of homeopathy
The philosophy of homeopathy is built around the
concept of vital force, this is understood to be a
dynamic life force which ‘steers all the functions
of life’.13 The concept of vital force was introduced
by Hahnemann in the early editions of the
Organon,14 and is based on the concept of
‘Vitalism’ which existed at that time.
‘The task of the vital force is to maintain har-
mony and order in the organism. Every com-
ponent of the organism, every organ and every
cell is influenced and guarded by the vital
force. The vital force protects us from ill.’13
According to this homeopathic approach, theorigin of disease lies in the disturbance of this
energy matrix not in the organic physical matrix
of the body, ‘The origins of illness are to be found in theweakened vital force.’13 Healing therefore must also
influence this vital force and homeopathic medi-
cines are believed to stimulate and strengthen the
vital force to promote self-healing and returning
them to equilibrium of mind, body and spirit.
‘The goal of homoeopathic treatment is not
to directly remove or suppress a symptom
rather to strengthen and harmonize the vital
force.’13
Later homeopaths such as Vithoulkas15 have ela-
borated on this concept to propose the primary
and secondary action of homeopathic remedies:
‘Every agent that acts upon the vitality, every
medicine, deranges more or less the vital
forces, and causes a certain alteration in the
health of the individual for a longer or shorter
period. This is termed primary action.
Although a product of the medicine and vital
powers conjointly, it is principally due to the
former power. To its action our vital force
endeavors to oppose its own energy. This
resistant action is a property, is indeed an auto-
matic action of our life-preserving power,
which goes by the name of secondary action
or counteraction.’15
The capacity to self-heal is therefore seen as an
innate ‘energy’ which can be strengthened and
stimulated by the application of the homeopathic
medicine because the medicine itself has been pre-pared by a series of dilutions and succussions to
reduce its primary effect of medication and
awaken its latent dynamic power:
‘By means of this manipulation of crude drugs
are produced preparations which only in
this way reach the full capacity to forcibly
influence the suffering parts of the sick organ-
ism.’ §27014
The correct selection of that medicine is of para-
mount importance because the choice requires the
therapies to take a detailed individual case history
during which the patient is required to describe
their symptoms. It has been suggested16 that
‘The non-specific therapeutic effects of the
doctor-patient relationship are likely to be
increased by the patient’s expectations of the
homeopathic method which meshes with the
specific therapeutic effects of the medicines.’
Self-healing and homeopathy
It is clear that homeopathy includes the concept of
self-healing in its philosophy and practice, and
there is a recognition that the ability to self-regu-
late or return to health is innate in humans.
Journal of the Royal Society of Medicine Short Reports
4 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Homeopaths attribute this to a ‘vital force’ and
believe that this innate process can be aided by
the administration of a specially prepared
‘remedy’ that supports the body in the process.
Homeopathy pays attention to the idea that phys-
ical changes relate to a prior ‘energetic’ change andthat good health encompasses spiritual, mental,
emotional and physical dimensions (Table 1).
Designing a clinical trial tomeasure the true placeboeffect
An important question remains as to how we sep-arate and measure the specific ‘medicine’ effects
from the non-specific ‘brain’ effects when we
attempt to evaluate homeopathy?
This dilemma was highlighted as early as
199511 when it was suggested that most authors
confuse the perceived placebo effect with the trueplacebo effect. The true placebo effect can only be
identified by including an untreated controlgroup in clinical trials. By doing so the other non-
specific effects that contribute to the perceived
placebo effect (such as natural course, regression
to the mean, other time effects and unidentified
parallel interventions), can be excluded.
Clinical trials
Two types of trial are therefore of interest when
considering these issues: those trials of homeop-
athy that compare a placebo group, active drug
group with a no treatment group and trials that
seek to reproduce specific effects of homeopathic
remedies.
In order to investigate the first group I con-
ducted a PubMed search of published work inthe last five years using the keywords
Homeopathy and Clinical Trials, excluding surveys
with no placebo, and those with animal and plant
subjects. Forty trials were identified of which only
three (7.5%) included a non-intervention group.
This analysis of the published work shows that
only a small percentage of trials of homeopathic
medicine use a non-participating control groupand that that this kind of group may be used for
different reasons. Future studies of homeopathy
should seek to include an untreated control
group in order to help distinguish the true placebo
effect from other nonspecific effects.
Trials that seek to reproducespecific effects of homeo-pathic remedies
A PubMed search using the terms ‘homeop-
athy’þ ‘specific’ and filtered to show clinicaltrials over the last five years in human subjects
returned only 10 studies (Table 2).
The eczema study17 showed that both homeo-
pathic and conventional treatment groups
improved similarly over a 12-month period but
as this was a observational study of a cohort
there was no control group and no placebo.
A migraine study18 showed improvement forpatients seeking homeopathic relief but the study
was designed to observe real-life conditions and
did not aim to determine the specific effect of a
homeopathic remedy. The study was also not
designed to measure the placebo effect.
The fifth study from the Institute for Social
Medicine, Epidemiology and Health Economics;
Charite University Medical Center; D-10098Berlin, Germany, concluded that while their
results confirm the toxicological and clinical
effects of Galphimia glauca compared to placebo,
the ICCH criteria for proving symptoms were not
suitable to distinguish between specific and
unspecific symptoms.
The work of Bell et al.19,20 explores the role of
electroencephalography (EEG) as a sensitive toolfor measuring the specific changes due to the
administration of homeopathic remedies.
Walach et al. take the most direct approach to
the question of specific vs. non-specific symptoms
of homeopathy. The 2001 study of the effects of
homeopathic Belladonna 30CH in healthy volun-
teers21 tested the hypothesis that symptoms pat-
terns are due to specific effects of a homeopathicremedy but found no indication that Belladonna
30CH produces symptoms different from placebo.
This was followed in 2004 by a pilot study
using a small number of participants and the
remedy Cantharis22 showed that homeopathic
proving symptoms appeared to be specific but
the trial needed replication. This was achieved
in 200823 and 200924 when they used a three-armed, double-blind, placebo-controlled rando-
mized study design in which volunteers took
either one of two homoeopathic remedies,
Natrum muriaticum or Arsenicum album in
30CH or identical placebo. Their main outcome
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 5
Tabl
e1.
Pub
Med
sear
chfo
rho
meo
path
y.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
Mul
tiwee
kre
stin
gEE
Gco
rdan
cech
ange
patt
erns
from
repe
ated
olfa
c-to
ryac
tivat
ion
with
two
cons
titut
ion-
ally
salie
ntho
meo
path
icre
med
ies
inhe
alth
yyo
ung
adul
ts.
Bel
lIR
,H
ower
ter
A,
Jack
son
N,
Bro
oks
AJ,
Sch
war
tzG
E.J
Alte
rnC
ompl
emen
tM
ed.
2012
May
;18(
5):4
45–5
3.P
MID
:22
5946
48[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Nin
ety-
seve
nyo
ung
adul
ts(N¼
97,m
ean
age
19ye
ars,
55%
wom
en)
with
good
self-
rate
dgl
obal
heal
than
dsc
reen
edfo
rho
meo
path
icco
nstit
utio
nalt
ypes
cons
iste
ntw
ithon
eof
two
rem
edie
s(e
ither
Sul
phur
orP
ulsa
tilla
)un
derw
ent
thre
ew
eekl
yla
bora
tory
sess
ions
.A
tea
chvi
sit,
subj
ects
had
5-m
inre
stin
g,ey
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lose
dEE
Gre
cord
ings
befo
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ter
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aceb
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ntro
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yac
tivat
ion
task
with
thei
rco
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nally
rele
vant
veru
mre
med
y.O
nere
med
ypo
tenc
y(6
c,12
c,or
30c)
used
per
wee
k,w
aspr
esen
ted
ina
rand
omiz
edor
der
over
the
thre
ese
ssio
ns.P
refr
onta
lres
ting
EEG
cord
ance
valu
esat
Fp1
and
Fp2
wer
eco
mpu
ted
from
arte
fact
-fre
e2-
min
EEG
sam
ples
from
the
pres
niff
ing
and
post
sniff
ing
rest
peri
ods.
Cor
danc
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rive
sfr
oman
algo
-ri
thm
that
inco
rpor
ates
abso
lute
and
rela
tive
EEG
valu
es.
No
Freq
uent
lyoc
curr
ing
pola
rsy
mpt
oms
asse
ssed
bysu
cces
sful
case
s.R
utte
nLA
,Fr
eiH
.H
omeo
path
y.20
12A
pr;1
01(2
):103
–11.
PM
ID:
2248
7370
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ina
pilo
tst
udy
30qu
estio
nsou
tof
ast
anda
rdqu
estio
nnai
rein
102
case
sre
spon
ding
wel
lto
five
med
icin
esw
ere
ana-
lyse
dan
dco
mpa
red
with
aco
ntro
lgro
upof
100
cons
ecut
ive
new
case
s.O
utco
mes
ofa
pivo
tta
ble,
Like
lihoo
dR
atio
(LR
)ca
lcul
atio
nsan
dM
ultiv
aria
teA
naly
sis
(MV
A)
wer
eco
mpa
red.
No
Hom
eopa
thic
med
icin
essu
bsta
ntia
llyre
duce
the
need
for
clot
ting
fact
orco
ncen
trat
esin
haem
ophi
liapa
tient
s:re
sults
ofa
blin
ded
plac
ebo
cont
rolle
dcr
oss
over
tria
l.
Kun
duT,
Sha
ikh
A,K
utty
A,
Nal
vade
A,
Kul
karn
iS
,K
ulka
rni
R,
Gho
shK
.H
omeo
path
y.20
12Ja
n;10
1(1)
:38–
43.
PM
ID:
2222
6313
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ina
sing
lebl
ind
plac
ebo
cont
rolle
dcr
oss
over
tria
l,28
cons
ecut
ive
pers
ons
with
haem
ophi
lia(P
WH
)w
ithse
vere
(24)
orm
oder
atel
yse
vere
(4)
dise
ase
rece
ived
stan
dard
man
agem
ent
with
plac
ebo
hom
eopa
thy
for
one
year
and
activ
eho
meo
path
ictr
eatm
ent
inth
esu
bseq
uent
year
with
the
sam
eco
nven
tiona
lm
anag
emen
t.Th
ere
was
now
ash
out
peri
od.
They
rece
ived
stan
dard
man
agem
ents
for
any
acut
eem
erge
ncy
duri
ngth
est
udy
peri
od.
Dev
elop
men
tof
inhi
bito
rdu
ring
the
stud
ype
riod
was
aw
ithdr
awal
crite
rion
.S
ampl
esi
zefo
rth
etr
ial
was
calc
ulat
edas
24P
WH
.Tr
ansf
usio
nre
quir
emen
ts,
blee
ding
scor
es,
pain
scor
esw
ere
eval
uate
dbl
ind
byin
depe
nden
tex
pert
s.H
omeo
path
icm
edic
ines
wer
ese
lect
edby
expe
rien
ced
hom
eopa
thic
phys
icia
nsde
pend
ing
oncl
inic
alco
nditi
onof
the
patie
nt.
Chi
-squ
ared
and
pair
edt
test
sw
ere
used
inst
atis
tical
anal
ysis
.
No
(continued)
Journal of the Royal Society of Medicine Short Reports
6 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
Rea
l-lif
eef
fect
ofcl
assi
cal
hom
eop-
athy
inth
etr
eatm
ent
ofal
lerg
ies:
am
ultic
ente
rpr
ospe
ctiv
eob
serv
atio
nal
stud
y.
Gru
ndlin
gC
,S
chim
etta
W,
Fras
sM
.W
ien
Klin
Woc
hens
chr.
2012
Jan;
124(
1–2)
:11–
17.
Epub
2011
Dec
8.P
MID
:22
1387
96[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Apr
ospe
ctiv
em
ultic
ente
rob
serv
atio
nal
stud
yw
asco
n-du
cted
byge
nera
lpra
ctiti
oner
ssp
ecia
lisin
gin
hom
eopa
thy
inni
neA
ustr
ian
test
cent
res.
Per
sona
lda
taan
dsy
mpt
oms
ofal
lerg
icpa
tient
sdi
agno
sed
with
alle
rgic
conj
unct
iviti
s,al
lerg
icrh
initi
s,br
onch
ial
asth
ma
and
neur
oder
mat
itis
befo
rean
daf
ter
hom
eopa
thic
trea
tmen
tw
ere
asse
ssed
bym
eans
ofqu
estio
nnai
res
(cla
ssifi
catio
nof
patie
nts’
cond
i-tio
nby
usin
gvi
sual
anal
ogue
scal
es/V
AS
).
No
Man
agem
ent
ofdi
stre
ssdu
ring
cli-
mac
teri
cye
ars
byho
meo
path
icth
erap
y.
Nay
akC
,Sin
ghV,
Sin
ghK
,S
ingh
H,
Gup
taJ,
Lam
baC
D,
Sha
rma
A,
Sha
rma
B,
Indi
raB
,B
huva
nesh
war
iS
,B
indr
aS
K,
Luxm
iK
S.
JA
ltern
Com
plem
ent
Med
.20
11N
ov;1
7(11
):103
7–42
.P
MID
:22
0876
13[P
ubM
ed–
inde
xed
for
MED
LIN
E]
An
open
,mul
ticen
tre,
pros
pect
ive,
obse
rvat
iona
lstu
dyw
asca
rrie
dou
tto
asce
rtai
nth
eus
eful
ness
ofho
meo
path
ictr
eatm
ent
indi
stre
ssdu
ring
clim
acte
ric
year
s(D
DC
Y).
Pat
ient
sw
ere
enro
lled
from
the
gene
ral
outp
atie
ntde
part
-m
ent
ofth
esi
xIn
stitu
tes/
Uni
tsof
Cen
tral
Cou
ncil
for
Res
earc
hin
Hom
oeop
athy
(CC
RH
)an
dw
ere
requ
ired
toco
mpl
ete
afo
llow
-up
peri
odof
one
year
aspe
rth
epr
otoc
olde
sign
edby
the
CC
RH
.A
unifo
rmqu
estio
nnai
reas
sess
ing
15pr
edef
ined
sym
ptom
sof
men
opau
sew
asad
opte
d,w
ithas
sess
men
tof
each
sym
ptom
atev
ery
visi
t.Le
vels
ofse
rum
FSH
and
lipid
prof
ilew
ere
mon
itore
dat
entr
yan
dat
com
-pl
etio
n.Ef
fect
size
ofth
est
udy
was
also
calc
ulat
ed.
CA
RA
Sof
twar
ew
asus
edfo
rre
pert
oriz
atio
nof
the
pres
entin
gsy
mpt
oms
ofm
enop
ause
alon
gw
ithth
ech
arac
teri
stic
attr
ibut
esof
each
patie
ntto
arri
veat
asi
mill
imum
.Th
ese
lect
edm
edic
ine
was
pres
crib
edin
asi
ngle
dose
aspe
rth
eho
meo
path
icpr
inci
ples
.Th
eas
sess
men
tof
the
resu
ltsw
asm
ade
thro
ugh
stat
istic
alan
alys
isus
ing
the
Wilc
oxon
sign
ed-r
ank
test
onS
tatis
tical
Pac
kage
for
Soc
ialS
cien
ces
(SP
SS
)co
mpa
ring
sym
ptom
scor
eat
entr
yan
dco
mpl
etio
nof
one
year
oftr
eatm
ent
and
tte
stfo
ran
alys
ing
impr
ove-
men
tin
labo
rato
ryfin
ding
s.
No
Mea
suri
ngth
eef
fect
iven
ess
ofho
meo
path
icca
reth
roug
hob
ject
ive
and
shar
edin
dica
tors
.
Leon
eL,
Mar
chiti
ello
M,
Nat
illi
M,
Rom
ano
MF.
Hom
eopa
thy.
2011
Oct
;100
(4):2
12–1
9.P
MID
:21
9621
95[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Indi
cato
rsof
hosp
italis
atio
nan
ddr
ugus
ew
ere
obta
ined
from
the
Hea
lthS
tatis
tical
Doc
umen
tatio
nS
yste
mof
Tusc
any
for
two
hom
eopa
thic
cent
res
inth
eLo
cal
Hea
lthA
utho
rity
ofP
isa,
Ital
y.C
ompa
red
hom
eopa
thic
user
sw
ithth
ege
nera
lpo
pula
tion
inth
esa
me
area
and
byco
mpa
ring
patie
nts
befo
rean
daf
ter
hom
eopa
thic
trea
tmen
t.
Yes
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 7
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
An
expl
orat
ory
stud
yon
scie
ntifi
cin
vest
igat
ions
inho
meo
path
yus
ing
med
ical
anal
yzer
.
Mis
hra
N,
Mur
alee
dhar
anK
C,
Par
anjp
eA
S,
Mun
taD
K,
Sin
ghH
,N
ayak
C.
JA
ltern
Com
plem
ent
Med
.20
11A
ug;1
7(8)
:705
–10.
PM
ID:
2178
7219
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Pre
-an
dpo
stin
terv
entio
nal
vari
abili
tysp
ectr
aof
hear
tra
tean
dbl
ood
flow
of77
subj
ects
wer
ere
cord
edw
ithth
eM
edic
alA
naly
zer
Sys
tem
,ad
min
iste
ring
hom
eopa
thic
prep
arat
ions
ofA
coni
tum
nape
llus
(6c,
10M
),A
rsen
icum
albu
m(2
00c,
1M
),G
else
miu
mse
mpe
rvir
ens
(200
c,1
M),
Pho
spho
rus
(200
c,1
M),
Pul
satil
lani
gric
ans
(200
c)an
dS
ulph
ur(2
00c,
1M
)ve
rsus
plac
ebo
cont
rol.
The
ampl
itude
ofth
epe
aks
viz.
low
-fre
quen
cy,
med
ium
-fre
quen
cy,
and
high
-fre
quen
cyw
asm
easu
red
for
post
inte
rven
tion
anal
ysis
.A
nin
crea
sein
the
ampl
itude
ofan
yva
lidpe
akby
100%
ora
decr
ease
by50
%w
asco
nsid
ered
assi
gnifi
cant
chan
ge.
No
The
feas
ibili
tyof
apr
agm
atic
rand
o-m
ised
cont
rolle
dtr
ialt
oco
mpa
reus
ual
care
with
usua
lca
repl
usin
divi
dua-
lised
hom
eopa
thy,
inch
ildre
nre
quir
ing
seco
ndar
yca
refo
ras
thm
a.
Thom
pson
EA,
Sha
wA
,N
icho
lJ,
Hol
lingh
urst
S,
Hen
ders
onA
J,Th
omps
onT,
Sha
rpD
.H
omeo
path
y.20
11Ju
l;100
(3):1
22–3
0.P
MID
:21
7843
28[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Ina
prag
mat
icpa
ralle
lgr
oup
rand
omis
edco
ntro
lled
tria
l(R
CT)
desi
gn,
child
ren
onst
ep2
orab
ove
ofth
eB
ritis
hTh
orac
icS
ocie
tyA
sthm
aG
uide
lines
(BTG
)w
ere
rand
omly
allo
cate
dto
UC
orU
Cpl
usa
five
visi
tpa
ckag
eof
hom
eo-
path
icca
re(H
C).
Out
com
em
easu
res
incl
uded
the
Juni
per
Ast
hma
Con
trol
Que
stio
nnai
re,Q
ualit
yof
Life
Que
stio
nnai
rean
da
reso
urce
use
ques
tionn
aire
.Q
ualit
ativ
ein
terv
iew
sw
ere
used
toga
infa
mili
es’a
ndhe
alth
prof
essi
onal
s’vi
ews
and
expe
rien
ces.
No
Hom
eopa
thic
Plu
mbu
mm
etal
licum
for
lead
pois
onin
g:a
rand
omiz
edcl
inic
altr
ial.
Pad
ilha
RQ
,R
iera
R,
Ata
llah
AN
.H
omeo
path
y.20
11Ju
l;100
(3):1
16–2
1.P
MID
:21
7843
27[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Dou
ble-
blin
dra
ndom
ized
tria
l.N
o
Hom
eopa
thic
ear
drop
sas
anad
junc
tto
stan
dard
ther
apy
inch
ildre
nw
ithac
ute
otiti
sm
edia
.
Tayl
orJA
,Ja
cobs
J.H
omeo
path
y.20
11Ju
l;100
(3):1
09–1
5.P
MID
:21
7843
26[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Chi
ldre
nw
ithA
OM
wer
een
rolle
din
the
stud
yat
the
time
ofdi
agno
sis
and
rand
omis
edto
rece
ive
eith
erst
anda
rdth
er-
apy
alon
eor
stan
dard
ther
apy
plus
aho
meo
path
icea
rdr
opso
lutio
nth
atw
asto
beus
edon
asne
eded
basi
sfo
rup
tofiv
eda
ys.P
aren
tsof
child
ren
inbo
thtr
eatm
entg
roup
sra
ted
the
seve
rity
of5
AO
Msy
mpt
oms
twic
eda
ilyfo
rfiv
eda
ysin
asy
mpt
omdi
ary.
Asy
mpt
omsc
ore
was
com
pute
dfo
rea
chas
sess
men
tw
ithlo
wer
scor
esde
notin
gle
ssse
vere
sym
p-to
ms.
Par
ents
ofch
ildre
nra
ndom
ised
tore
ceiv
eea
rdr
ops
also
reco
rded
info
rmat
ion
rega
rdin
gsy
mpt
oms
bein
gtr
ea-
ted
and
resp
onse
totr
eatm
ent.
No
(continued)
Journal of the Royal Society of Medicine Short Reports
8 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
An
initi
alre
port
onth
eef
ficac
yof
am
illes
imal
pote
ncy
Ars
enic
umA
lbum
LM0/
3in
amel
iora
ting
arse
nic
toxi
city
inhu
man
sliv
ing
ina
high
-ris
kar
seni
cvi
llage
.
Khu
da-B
ukhs
hA
R,
Ban
erje
eA
,B
isw
asS
J,K
arm
akar
SR
,B
aner
jee
P,P
atha
kS
,G
uha
B,
Haq
ueS
,D
asD
,D
eA
,D
asD
,B
ouje
dain
iN
.X
iZ,
He
YJan
dB
aoX
.20
11Ju
n;9(
6):5
96–6
04.
PM
ID:
2166
9162
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
This
stud
yw
asca
rrie
dou
ton
volu
ntee
rsliv
ing
inan
arse
nic-
affe
cted
villa
gew
here
noar
seni
c-fr
eedr
inki
ngw
ater
isav
aila
ble.
Twen
ty-e
ight
volu
ntee
rsfr
omth
evi
llage
ofD
asdi
ya,
inH
arin
ghat
abl
ock
unde
rN
adia
Dis
tric
t,W
est
Ben
gal,
Indi
a,an
arse
nic-
cont
amin
ated
villa
gew
here
wel
lsco
ntai
n55
to95m
g/L
arse
nic,
wer
ese
lect
edto
unde
rtak
ea
doub
le-b
lind
and
plac
ebo-
cont
rolle
dtr
ial.
The
subj
ects
prov
ided
sam
ples
ofbl
ood
and
urin
ebe
fore
and
afte
rtw
om
onth
sof
taki
ngei
ther
‘ver
um’
or‘p
lace
bo’.
Ano
ther
18su
bjec
tsliv
ing
inan
arse
nic-
free
villa
gese
rved
asth
ene
gativ
eco
ntro
ls.
Yes
Pul
pade
ntis
D30
for
acut
ere
vers
ible
pulp
itis:
apr
ospe
ctiv
eco
hort
stud
yin
rout
ine
dent
alpr
actic
e.
Ham
reH
J,M
ittag
I,G
lock
man
nA
,K
iene
H,
Trog
erW
.A
ltern
Ther
Hea
lthM
ed.
2011
Jan–
Feb;
17(1
):16–
21.
PM
ID:
2161
4940
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Pro
spec
tive,
obse
rvat
iona
l,op
en-l
abel
,si
ngle
-arm
coho
rtst
udy.
No
Hom
eopa
thy
for
depr
essi
on–
DEP
-H
OM
:stu
dypr
otoc
olfo
ra
rand
omiz
ed,
part
ially
doub
le-b
lind,
plac
ebo
con-
trol
led,
four
arm
edst
udy.
Adl
erU
C,
Kru
ger
S,
Teut
M,
Ludt
keR
,B
arts
chI,
Sch
utzl
erL,
Mel
cher
F,W
illic
hS
N,
Lind
eK
,W
ittC
M.
Tria
ls.2
011
Feb
14;1
2(1)
:43.
PM
ID:
2132
0338
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ara
ndom
ised
,pa
rtia
llydo
uble
-blin
d,pl
aceb
o-co
ntro
lled,
four
-arm
edtr
ial
usin
ga
2�
2fa
ctor
ial
desi
gnw
itha
six-
wee
kst
udy
dura
tion
per
patie
ntw
illbe
perf
orm
ed.
228
patie
nts
diag
nose
dw
ithm
ajor
depr
essi
on(m
oder
ate
epi-
sode
)by
aps
ychi
atri
stw
illbe
incl
uded
.Th
epr
imar
yen
d-po
int
isth
eto
tal
scor
eon
the
17-i
tem
Ham
ilton
Dep
ress
ion
Rat
ing
Sca
leaf
ter
six
wee
ks.
Sec
onda
ryen
dpo
ints
are:
Ham
ilton
Dep
ress
ion
Rat
ing
Sca
leto
tals
core
afte
rtw
oan
dfo
urw
eeks
;res
pons
ean
dre
mis
sion
rate
s,B
eck
Dep
ress
ion
inve
ntor
yto
tal
scor
e,qu
ality
oflif
ean
dsa
fety
attw
o,fo
uran
dsi
xw
eeks
.S
tatis
tical
anal
yses
will
beby
inte
ntio
n-to
-tr
eat.
The
mai
nen
dpoi
ntw
illbe
anal
ysed
bya
two-
fact
oria
lan
alys
isof
cova
rian
ce.
With
inth
ism
odel
gene
ralis
edes
ti-m
atio
neq
uatio
nsw
illbe
used
toes
timat
edi
ffer
ence
sbe
twee
nve
rum
and
plac
ebo,
and
betw
een
both
type
sof
case
hist
ory.
No
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 9
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
Hom
eopa
thy
has
clin
ical
bene
fits
inrh
eum
atoi
dar
thri
tispa
tient
sth
atar
eat
trib
utab
leto
the
cons
ulta
tion
pro-
cess
but
not
the
hom
eopa
thic
rem
edy:
ara
ndom
ized
cont
rolle
dcl
inic
altr
ial.
Bri
enS
,La
chan
ceL,
Pre
scot
tP,
McD
erm
ott
C,
Lew
ithG
.R
heum
atol
ogy
(Oxf
ord)
.20
11Ju
n;50
(6):1
070–
82.
Epub
2010
Nov
13.
PM
ID:
2107
6131
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Expl
orat
ory
doub
le-b
lind,
rand
omis
edpl
aceb
o-co
ntro
lled
tria
lco
nduc
ted
from
Janu
ary
2008
toJu
ly20
08,
inpa
tient
sw
ithac
tive
stab
leR
Are
ceiv
ing
conv
entio
nal
ther
apy.
Eigh
ty-t
hree
part
icip
ants
from
thre
ese
cond
ary
care
UK
outp
atie
ntcl
inic
sw
ere
rand
omiz
edto
24w
eeks
oftr
eatm
ent
with
eith
erho
meo
path
icco
nsul
tatio
n(f
urth
erra
ndom
ized
toin
divi
dual
ized
hom
eopa
thy,
com
plex
hom
eopa
thy
orpl
a-ce
bo)
orno
n-ho
meo
path
icco
nsul
tatio
n(f
urth
erra
ndom
ized
toco
mpl
exho
meo
path
yor
plac
ebo)
.Co-
prim
ary
outc
omes
:A
CR
20%
impr
ovem
ent
(AC
R20
)cr
iteri
aan
dpa
tient
mon
thly
glob
alas
sess
men
t(G
A).
Sec
onda
ryou
tcom
es:2
8-jo
int
DA
S(D
AS
-28)
,te
nder
and
swol
len
join
tco
unt,
dise
ase
seve
rity
,pa
in,
wee
kly
patie
ntan
dph
ysic
ian
GA
and
pain
,an
din
flam
mat
ory
mar
kers
.
No
Effe
cts
ofho
meo
path
icm
edic
ines
onpo
lyso
mno
grap
hic
slee
pof
youn
gad
ults
with
hist
orie
sof
coff
ee-r
elat
edin
som
nia.
Bel
lIR
,H
ower
ter
A,
Jack
son
N,
Aic
kin
M,
Bal
dwin
CM
,B
ootz
inR
R.
Sle
epM
ed.
2011
May
;12(
5):5
05–1
1.Ep
ub20
10Ju
l29
.P
MID
:20
6736
48[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Youn
gad
ults
ofbo
thse
xes
(age
s18
–31)
with
abov
e-av
erag
esc
ores
onst
anda
rdiz
edpe
rson
ality
scal
esfo
rei
ther
cyni
cal
host
ility
oran
xiet
yse
nsiti
vity
(but
not
both
)an
da
hist
ory
ofco
ffee
-ind
uced
inso
mni
apa
rtic
ipat
edin
the
mon
th-l
ong
stud
y.A
t-ho
me
poly
som
nogr
aphi
cre
cord
ings
wer
eob
tain
edon
succ
essi
vepa
irs
ofni
ghts
once
per
wee
kfo
ra
tota
lof
eigh
tre
cord
ings
(nig
hts
1,2,
8,9,
15,
16,
22,
23).
Sub
ject
s(N¼
54)
rece
ived
plac
ebo
pelle
tson
nigh
t8
(sin
gle-
blin
d)an
dve
rum
pelle
tson
nigh
t22
(dou
ble-
blin
d)in
30c
dose
sof
one
oftw
oho
meo
path
icre
med
ies,
Nux
Vom
ica
orC
offe
aC
ruda
.S
ubje
cts
com
plet
edda
ilym
orni
ngsl
eep
diar
ies
and
wee
kly
Pitt
sbur
ghsl
eep
qual
ityin
dex
scal
es,
asw
ell
aspr
ofile
ofm
ood
stat
essc
ales
atbe
dtim
eon
poly
som
nogr
aphy
nigh
ts.
No
Pro
toco
lfo
ra
phas
e1
hom
eopa
thic
drug
prov
ing
tria
l.Te
utM
,H
irsc
hber
gU
,Lu
edtk
eR
,S
chne
ggC
,D
ahle
rJ,
Alb
rech
tH
,W
ittC
M.
Tria
ls.
2010
Jul
22;1
1:80
.P
MID
:20
6499
79[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Mul
ti-ce
ntre
,ra
ndom
ised
,do
uble
-blin
d,pl
aceb
o-co
ntro
lled
phas
e1
tria
lwith
30he
alth
yvo
lunt
eers
.The
stud
yco
nsis
tsof
ase
ven
day
run-
inpe
riod
,a
five-
day
inte
rven
tion
peri
odan
da
16-d
aypo
st-i
nter
vent
ion
obse
rvat
ion
peri
od.S
ubje
cts,
inve
stig
ator
san
dth
est
atis
ticia
nsar
ebl
inde
dfr
omth
eal
loca
tion
toth
est
udy
arm
and
from
the
iden
tity
ofth
eho
meo
path
icdr
ug.
The
inte
rven
tion
isa
high
lydi
lute
dho
meo
path
icdr
ug(p
oten
cyC
12¼
1024
),D
ose:
five
glob
ules
take
nfiv
etim
espe
rda
yov
era
max
imum
peri
odof
five
days
.
No
(continued)
Journal of the Royal Society of Medicine Short Reports
10 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
The
plac
ebo
cons
ists
ofan
optic
ally
iden
tical
carr
ier
sub-
stan
ce(s
ucro
segl
obul
es).
Sub
ject
sdo
cum
ent
the
sym
p-to
ms
they
expe
rien
cein
ase
mi-
stru
ctur
edon
line
diar
y.Th
epr
imar
you
tcom
epa
ram
eter
isth
enu
mbe
rof
spec
ific
sym
ptom
sth
atch
arac
teri
seth
ein
terv
entio
nco
mpa
red
toth
epl
aceb
oaf
ter
ape
riod
ofth
ree
wee
ks.
Sec
onda
ryou
t-co
me
para
met
ers
are
qual
itativ
edi
ffer
ence
sin
prof
iles
ofch
arac
teri
stic
and
prov
ing
sym
ptom
san
dth
eto
tal
num
ber
ofal
lpr
ovin
gsy
mpt
oms.
The
num
ber
ofsy
mpt
oms
will
bequ
antit
ativ
ely
anal
ysed
onan
inte
ntio
n-to
-tre
atba
sis
usin
gA
NC
OV
Aw
ithth
esu
bjec
t’sex
pect
atio
nan
dba
selin
eva
lues
asco
vari
ates
.C
onte
ntan
alys
isac
cord
ing
toM
ayri
ngis
adap
ted
tosu
itth
eho
meo
path
icqu
alita
tive
anal
ysis
proc
edur
e.
Hom
eopa
thic
trea
tmen
tof
patie
nts
with
mig
rain
e:a
pros
pect
ive
obse
rva-
tiona
lst
udy
with
a2-
year
follo
w-u
ppe
riod
.
Witt
CM
,Lu
dtke
R,
Will
ich
SN
.J
Alte
rnC
ompl
emen
tM
ed.
2010
Apr
;16(
4):3
47–5
5.P
MID
:20
4232
06[P
ubM
ed–
inde
xed
for
MED
LIN
E]
This
was
apr
ospe
ctiv
em
ultic
ente
rob
serv
atio
nal
stud
y.C
onse
cutiv
epa
tient
sbe
ginn
ing
hom
eopa
thic
trea
tmen
tin
prim
ary
care
prac
tices
wer
eev
alua
ted
over
two
year
sus
ing
stan
dard
ized
ques
tionn
aire
s.Th
eda
tare
cord
edin
clud
eddi
agno
ses
(Int
erna
tiona
lC
lass
ifica
tion
ofD
isea
ses,
Nin
thR
evis
ion)
and
curr
ent
com
plai
nts,
incl
udin
gth
eir
seve
rity
(num
eric
ratin
gsc
ale¼
0–10
),he
alth
-rel
ated
qual
ityof
life
(QoL
,36
-ite
mS
hort
-For
mH
ealth
Sur
vey)
,m
edic
alhi
stor
y,co
nsul
tatio
ns,
hom
eopa
thic
and
conv
entio
nal
trea
tmen
ts,
asw
ell
asot
her
heal
thse
rvic
eus
e.
No
Trau
mee
lS
for
pain
relie
ffo
llow
ing
hallu
xva
lgus
surg
ery:
ara
ndom
ized
cont
rolle
dtr
ial.
Sin
ger
SR
,A
mit-
Koh
nM
,W
eiss
S,
Ros
enbl
umJ,
Mao
zG
,S
amue
lsN
,Lu
kasi
ewic
zE,
Free
dman
L,P
altie
lO
,It
zcha
kiM
,N
iska
M,
Obe
rbau
mM
.B
MC
Clin
Pha
rmac
ol.2
010
Apr
12;1
0:9.
PM
ID:
2038
0750
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
We
perf
orm
eda
rand
omiz
ed,
doub
le-b
lind,
plac
ebo-
con-
trol
led
tria
lto
eval
uate
the
effic
acy
ofth
eho
meo
path
icpr
epar
atio
nTr
aum
eel
Sin
min
imis
ing
post
-ope
rativ
epa
inan
dan
alge
sic
cons
umpt
ion
follo
win
gsu
rgic
alco
rrec
tion
ofha
llux
valg
us.E
ight
yco
nsec
utiv
epa
tient
sw
ere
rand
omiz
edto
rece
ive
eith
erTr
aum
eel
tabl
ets
oran
indi
stin
guis
habl
epl
aceb
o,an
dto
okpr
imar
yan
dre
scue
oral
anal
gesi
csas
need
ed.
Max
imum
num
eric
alpa
insc
ores
atre
stan
dco
n-su
mpt
ion
ofor
alan
alge
sics
wer
ere
cord
edon
day
ofsu
r-ge
ryan
dfo
r13
days
follo
win
gsu
rger
y.
No
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 11
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
No
effe
ctof
aho
moe
opat
hic
com
bin-
atio
nof
Arn
ica
mon
tana
and
Bry
onia
alba
onbl
eedi
ng,
infla
mm
atio
n,an
dis
chae
mia
afte
rao
rtic
valv
esu
rger
y.
Cor
nuC
,Jos
eph
P,G
ailla
rdS
,B
auer
C,
Ved
rinn
eC
,B
isse
ryA
,M
elot
G,
Bos
sard
N,
Bel
onP,
Leho
tJJ
.B
rJ
Clin
Pha
rmac
ol.
2010
Feb;
69(2
):136
–42.
PM
ID:
2023
3176
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
One
day
befo
resu
rger
y,92
adul
tpa
tient
sw
ere
rand
omly
assi
gned
toa
doub
le-b
lind
para
llel
tria
lw
ithei
ther
hom
-oe
opat
hic
gran
ules
ora
mat
chin
gpl
aceb
oun
til4
days
afte
rsu
rger
y.Th
epr
imar
you
tcom
ew
asth
evo
lum
eof
bloo
d/liq
uid
inth
edr
ains
atth
eir
rem
oval
.Th
ese
cond
ary
out-
com
esin
clud
edpo
stop
erat
ive
bloo
d/liq
uid
loss
esat
12an
d24
has
wel
las
C-r
eact
ive
prot
ein
(CR
P),
pain
,te
mpe
ratu
rean
dpl
asm
atr
opon
inIc
.
No
Hom
eopa
thic
trea
tmen
tof
elde
rly
patie
nts
–a
pros
pect
ive
obse
rvat
iona
lst
udy
with
follo
w-u
pov
era
two
year
peri
od.
Teut
M,
Ludt
keR
,S
chna
bel
K,
Will
ich
SN
,W
ittC
M.
BM
CG
eria
tr.
2010
Feb
22;1
0:10
.P
MID
:20
1758
87[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Inth
issu
bgro
upan
alys
isof
apr
ospe
ctiv
e,m
ultic
entr
eco
hort
stud
yto
tally
incl
udin
g39
81pa
tient
str
eate
dby
hom
eopa
thic
phys
icia
nsin
prim
ary
care
prac
tices
inG
erm
any
and
Sw
itzer
land
,da
taw
asan
alys
edfr
omal
lpa
tient
s>
70ye
ars
cons
ultin
gth
eph
ysic
ian
for
the
first
time.
The
mai
nou
tcom
em
easu
res
wer
e:as
sess
men
tby
patie
ntof
the
seve
rity
ofco
mpl
aint
s(n
umer
icra
ting
scal
es)
and
qual
ityof
life
(SF-
36)a
ndby
the
phys
icia
nof
the
seve
rity
ofdi
agno
ses
(num
eric
ratin
gsc
ales
)atb
asel
ine,
and
afte
r3,
12,
and
24m
onth
s.
No
Chr
onic
prim
ary
inso
mni
a:ef
ficac
yof
hom
eopa
thic
sim
illim
um.
Nau
deD
F,S
teph
anie
Cou
chm
anIM
,M
ahar
ajA
.
Hom
eopa
thy.
2010
Jan;
99(1
):63–
8.Er
ratu
min
:H
omeo
path
y.20
10A
pr;9
9(2)
:151
.P
MID
:20
1291
78[P
ubM
ed–
inde
xed
for
MED
LIN
E]
30pa
rtic
ipan
tsw
ere
sele
cted
inac
cord
ance
with
DS
M-I
VTR
(200
0)(1
)cr
iteri
on30
7.42
Pri
mar
yIn
som
nia
and
then
rand
omly
divi
ded
betw
een
trea
tmen
tan
dpl
aceb
ogr
oups
.Th
em
easu
rem
ent
tool
sus
edw
ere
aS
leep
Dia
ry(S
D)
and
the
Sle
epIm
pair
men
tIn
dex
(SII
).(2
)A
fter
anin
itial
con-
sulta
tion,
two
follo
w-u
pco
nsul
tatio
nsat
two-
wee
kin
terv
als
took
plac
e.H
omeo
path
icm
edic
atio
nw
aspr
escr
ibed
atth
efir
stan
dse
cond
cons
ulta
tions
.Th
eS
IIw
asco
mpl
eted
atea
chco
nsul
tatio
nan
dpa
rtic
ipan
tsw
ere
inst
ruct
edat
the
first
cons
ulta
tion
tost
art
the
SD
.
No
[Eff
ectiv
enes
sof
acl
assi
cal
hom
eo-
path
ictr
eatm
ent
inat
opic
ecze
ma.
Ara
ndom
ised
plac
ebo-
cont
rolle
ddo
uble
-blin
dcl
inic
altr
ial].
Sie
benw
irth
J,Lu
dtke
R,
Rem
yW
,Rak
oski
J,B
orel
liS
,R
ing
J.Fo
rsch
Kom
plem
entm
ed.
2009
Oct
;16(
5):3
15–2
3.Ep
ub20
09S
ep3.
Ger
man
.P
MID
:19
8878
10[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Sin
gle-
cent
re,
rand
omis
ed,
doub
le-b
lind
clin
ical
tria
lco
m-
pari
ngho
meo
path
icre
med
ies
with
plac
ebo
inyo
ung
adul
ts(a
ge18
–35)
with
atop
icde
rmat
itis.
Hom
eopa
thic
rem
edie
sw
ere
indi
vidu
ally
adm
inis
tere
dac
cord
ing
toth
eru
les
ofcl
assi
calh
omeo
path
y.A
fter
anun
trea
ted
base
line
peri
odof
four
wee
ks,
all
patie
nts
wer
etr
eate
dan
dm
onito
red
for
32w
eeks
.Thr
ough
outt
hest
udy,
co-m
edic
atio
nw
asal
low
ed
No
(continued)
Journal of the Royal Society of Medicine Short Reports
12 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
only
with
indi
ffer
ent
emol
lient
s.Th
em
ain
outc
ome
para
m-
eter
was
dise
ase
seve
rity
asas
sess
edby
Cos
taan
dS
aura
t’sm
ulti-
para
met
erat
opic
derm
atiti
ssc
ore
(MP
-sc
ore)
.
Hom
oeop
athi
cve
rsus
conv
entio
nal
ther
apy
for
atop
icec
zem
ain
child
ren:
med
ical
and
econ
omic
resu
lts.
Witt
CM
,B
rink
haus
B,
Pac
hD
,Rei
nhol
dT,
Wru
ckK
,R
oll
S,
Jack
elT,
Sta
abD
,W
egsc
heid
erK
,W
illic
hS
N.
Der
mat
olog
y.20
09;2
19(4
):329
–40.
Epub
2009
Oct
13.
PM
ID:
1982
8937
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ina
pros
pect
ive
mul
ticen
tre
com
para
tive
obse
rvat
iona
lno
n-ra
ndom
ised
stud
y,13
5ch
ildre
n(h
omeo
path
yn¼
48vs
.co
nven
tiona
ln¼
87)
with
mild
tom
oder
ate
atop
icec
zem
aw
ere
incl
uded
.Th
epr
imar
you
tcom
ew
asth
eS
CO
RA
D(S
cori
ngA
topi
cD
erm
atiti
s)at
6m
onth
s.Fu
rthe
rou
tcom
esat
six
and
12m
onth
sal
soin
clud
edqu
ality
oflif
eof
pare
nts
and
child
ren,
use
ofco
nven
tiona
lm
edic
ine,
trea
tmen
tsa
fety
and
dise
ase-
rela
ted
cost
s.
No
Effe
ctiv
enes
sof
the
hom
eopa
thic
prep
arat
ion
Neu
rexa
nco
mpa
red
with
that
ofco
mm
only
used
vale
rian
-bas
edpr
epar
atio
nsfo
rth
etr
eatm
ent
ofne
r-vo
usne
ss/r
estle
ssne
ss–
anob
serv
a-tio
nal
stud
y.
Hub
ner
R,
van
Has
elen
R,
Kle
inP.
Sci
entif
icW
orld
Jour
nal.
2009
Aug
11;9
:733
–45.
PM
ID:
1970
5035
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Apr
ospe
ctiv
e,no
nran
dom
ized
,no
nint
erve
ntio
nal,
obse
rva-
tiona
lst
udy,
usin
gco
nven
tiona
lor
CA
Mpr
actic
es,
was
cond
ucte
din
49G
erm
anpr
actic
es.
Each
prac
tice
coul
din
clud
eup
to15
subj
ects
trea
ted
with
eith
erth
eho
meo
-pa
thic
prep
arat
ion
Neu
rexa
nor
with
com
bina
tion
form
ula-
tions
base
don
vale
rian
extr
acts
.Th
ere
was
nopl
aceb
ogr
oup.
No
Hom
eopa
thic
trea
tmen
tof
min
orap
h-th
ous
ulce
r:a
rand
omiz
ed,
plac
ebo-
cont
rolle
dcl
inic
altr
ial.
Mou
savi
F,M
ojav
erYN
,A
sadz
adeh
M,
Mir
zaza
deh
M.
Hom
eopa
thy.
2009
Jul;9
8(3)
:137
–41.
PM
ID:
1964
7206
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ara
ndom
ized
,si
ngle
blin
d,pl
aceb
o-co
ntro
lled
clin
ical
tria
lof
indi
vidu
alis
edho
meo
path
y.O
nehu
ndre
dpa
tient
sw
ithm
inor
apht
hous
ulce
rw
ere
trea
ted
with
indi
vidu
alis
edho
meo
path
icm
edic
ines
orpl
aceb
oan
dfo
llow
edup
for
six
days
.P
atie
nts
rece
ived
two
dose
sof
indi
vidu
alis
edho
meo
path
icm
edic
ines
inth
e6
Cpo
tenc
yas
oral
liqui
dat
base
line
and
12h
late
r.P
ain
inte
nsity
and
ulce
rsi
zew
ere
reco
rded
atba
selin
edu
ring
and
atth
een
dof
the
tria
l(m
orni
ngs
ofda
ys4
and
6).
No
Mon
thly
itrac
onaz
ole
vers
uscl
assi
cho
meo
path
yfo
rth
etr
eatm
ent
ofre
curr
ent
vulv
ovag
inal
cand
idia
sis:
ara
ndom
ised
tria
l.
Witt
A,
Kau
fman
nU
,B
itsch
nau
M,
Tem
pfer
C,
Ozb
alA
,H
ayto
uglu
E,G
rego
rH
,K
iss
H.
BJO
G.
2009
Oct
;116
(11)
:149
9–50
5.Ep
ub20
09Ju
l7.
PM
ID:
1958
3713
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Wom
enw
ere
rand
omis
edin
toth
ree
grou
ps:
itrac
onaz
ole
with
lact
obac
illi
(gro
up1)
,itr
acon
azol
ew
ithou
tla
ctob
acill
i(g
roup
2)an
dC
H(g
roup
3).I
trac
onaz
ole
trea
tmen
tof
acut
ein
fect
ion
was
follo
wed
bya
6-m
onth
mai
nten
ance
regi
men
with
mon
thly
sing
le-d
ayitr
acon
azol
e(2
00m
gbi
d).W
omen
ingr
oup
1w
ere
give
nad
ditio
nalv
agin
alla
ctob
acill
ifor
6da
yspe
rm
onth
thro
ugho
utth
em
aint
enan
cere
gim
enTh
erea
fter
,pa
tient
sw
ere
follo
wed
with
out
trea
tmen
tfo
rsi
xm
onth
s.C
Htr
eatm
ent
was
perf
orm
edfo
r12
mon
ths
No
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 13
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
Hom
eopa
thic
path
ogen
etic
tria
lspr
o-du
cesp
ecifi
csy
mpt
oms
diff
eren
tfr
ompl
aceb
o.
Mol
linge
rH
,S
chne
ider
R,
Wal
ach
H.
Fors
chK
ompl
emen
tmed
.20
09A
pr;1
6(2)
:105
–10.
Epub
2009
Apr
9.P
MID
:19
4209
56[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Thre
ear
med
,do
uble
-blin
d,pl
aceb
oco
ntro
lled
rand
omis
edex
peri
men
tal
path
ogen
etic
stud
yin
25he
alth
yvo
lunt
eers
who
took
eith
eron
eof
two
hom
eopa
thic
rem
edie
s,N
atru
mm
uria
ticum
and
Ars
enic
umal
bum
in30
CH
orid
entic
alpl
a-ce
bo.M
ain
outc
ome
para
met
erw
asth
enu
mbe
rof
rem
edy-
spec
ific
sym
ptom
spe
rgr
oup.
No
Hea
lthca
repr
ovid
edby
aho
meo
path
asan
adju
nct
tous
ual
care
for
Fibr
omya
lgia
(FM
S):
resu
ltsof
api
lot
Ran
dom
ised
Con
trol
led
Tria
l.
Rel
ton
C,
Sm
ithC
,R
awJ,
Wal
ters
C,
Ade
bajo
AO
,Th
omas
KJ,
Youn
gTA
.H
omeo
path
y.20
09A
pr;9
8(2)
:77–
82.
PM
ID:
1935
8959
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ina
prag
mat
icpa
ralle
lgr
oup
RC
Tde
sign
,ad
ults
with
adi
agno
sis
ofFM
S(A
CR
crite
ria)
wer
era
ndom
lyal
loca
ted
tous
ual
care
orus
ual
care
plus
adju
nctiv
eca
reby
aho
meo
-pa
th.
Adj
unct
ive
care
cons
iste
dof
five
inde
pth
inte
rvie
ws
and
indi
vidu
alis
edho
meo
path
icm
edic
ines
.Th
epr
imar
you
tcom
em
easu
rew
asth
edi
ffer
ence
inFi
brom
yalg
iaIm
pact
Que
stio
nnai
re(F
IQ)
tota
lsc
ore
at22
wee
ks.
No
Hom
eopa
thic
trea
tmen
tof
patie
nts
with
dysm
enor
rhea
:a
pros
pect
ive
obse
rvat
iona
lst
udy
with
2ye
ars
follo
w-u
p.
Witt
CM
,Lu
dtke
R,
Will
ich
SN
.A
rch
Gyn
ecol
Obs
tet.
2009
Oct
;280
(4):6
03–1
1.Ep
ub20
09Fe
b20
.P
MID
:19
2295
44[P
ubM
ed–
inde
xed
for
MED
LIN
E]
Pro
spec
tive
mul
ticen
ter
obse
rvat
iona
lstu
dyin
prim
ary
care
,us
ing
stan
dard
ized
ques
tionn
aire
sto
reco
rdfo
rtw
oye
ars
dise
ases
,qu
ality
oflif
e,m
edic
alhi
stor
y,co
nsul
tatio
ns,
all
trea
tmen
ts,
othe
rhe
alth
serv
ices
use.
No
Igna
tiain
the
trea
tmen
tof
oral
liche
npl
anus
.M
ousa
viF,
She
rafa
tiS
,M
ojav
erYN
.H
omeo
path
y.20
09Ja
n;98
(1):4
0–4.
PM
ID:
1913
5958
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Inth
issi
ngle
blin
dra
ndom
ized
cont
rol
clin
ical
tria
l,30
cons
ecut
ive
patie
nts
with
oral
lesi
ons
cons
iste
ntcl
inic
ally
and
hist
olog
ical
lyw
ither
osiv
ean
d/or
atro
phic
OLP
wer
ere
crui
ted.
The
patie
nts
wer
era
ndom
lydi
vide
din
totw
ogr
oups
tore
ceiv
eIg
natia
orpl
aceb
o.Th
eyw
ere
trea
ted
for
four
mon
ths.
No
Eval
uatio
nof
the
qual
ityof
life
afte
rin
divi
dual
ized
hom
eopa
thic
trea
tmen
tfo
rse
ason
alal
lerg
icrh
initi
s.A
pro-
spec
tive,
open
,no
n-co
mpa
rativ
est
udy.
Goo
ssen
sM
,Lae
kem
anG
,A
ertg
eert
sB
,B
untin
xF;
AR
CH
stud
ygr
oup.
Hom
eopa
thy.
2009
Jan;
98(1
):11–
16.
PM
ID:
1913
5954
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Apr
ospe
ctiv
e,op
en,n
on-c
ompa
rativ
est
udy
was
cond
ucte
din
Bel
gium
.Pat
ient
sag
edbe
twee
n14
and
68ye
ars
with
SA
Rw
ere
trea
ted
byon
eof
seve
nho
meo
path
icph
ysic
ians
.P
atie
nts
com
plet
edth
eR
QLQ
atba
selin
ean
dag
ain
afte
rth
ree
and
four
wee
ksof
hom
eopa
thic
trea
tmen
t.
No
(continued)
Journal of the Royal Society of Medicine Short Reports
14 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
How
heal
thy
are
chro
nica
llyill
patie
nts
afte
rei
ght
year
sof
hom
eopa
thic
trea
tmen
t?–
Res
ults
from
alo
ngte
rmob
serv
atio
nal
stud
y.
Witt
CM
,Lu
dtke
R,
Men
gler
N,
Will
ich
SN
.B
MC
Pub
licH
ealth
.20
08D
ec17
;8:4
13.
PM
ID:
1909
1085
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ina
pros
pect
ive,
mul
ticen
tre
coho
rtst
udy
with
103
hom
eopa
thic
prim
ary
care
prac
tices
inG
erm
any
and
Sw
itzer
land
,dat
afr
omal
lpat
ient
s(a
ge>
1ye
ar)
cons
ultin
gth
eph
ysic
ian
for
the
first
time
wer
eob
serv
ed.
The
mai
nou
tcom
em
easu
res
wer
e:th
epa
tient
s’pe
rcei
ved
chan
gein
com
plai
ntse
veri
ty(n
umer
icra
ting
scal
esfr
om0¼
noco
mpl
aint
to10¼
max
imal
seve
rity
)an
dqu
ality
oflif
eas
mea
sure
dby
the
SF-
36at
base
line,
and
afte
rtw
oan
dei
ght
year
s.
No
Aho
moe
opat
hic
prov
ing
ofG
alph
imia
glau
ca.
Teut
M,D
ahle
rJ,
Sch
negg
C;
Wils
ede
Stu
dyG
roup
for
Hom
oeop
athi
cP
rovi
ngs.
Fors
chK
ompl
emen
tmed
.20
08A
ug;1
5(4)
:211
–17.
Epub
2008
Aug
15.
PM
ID:
1878
7330
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Ran
dom
ised
,do
uble
-blin
d,pl
aceb
o-co
ntro
lled
tria
lw
itha
one-
wee
kba
selin
e,fo
ur-w
eek
prov
ing,
and
two-
wee
kpo
st-
obse
rvat
iona
lpe
riod
.S
ubje
cts:
15he
alth
yph
ysic
ians
and
med
ical
stud
ents
volu
ntee
red
aspr
over
s;11
wer
era
ndo-
mis
edto
veru
man
dfo
urto
plac
ebo.
Pro
ving
subs
tanc
e:ga
lphi
mia
glau
caC
12co
mpa
red
topl
aceb
o;m
axim
umin
take
offiv
eda
ys.
Out
com
em
easu
res:
prov
ing
sym
ptom
sac
cord
ing
toIC
CH
defin
ition
and
the
num
ber
ofpr
ovin
gsy
mpt
oms.
The
prov
ing
sym
ptom
sw
ere
anal
ysed
qual
ita-
tivel
yus
ing
the
Boe
nnin
ghau
sen
met
hod.
No
Hom
eopa
thic
path
ogen
etic
tria
lspr
o-du
cem
ore
spec
ific
than
non-
spec
ific
sym
ptom
s:re
sults
from
two
doub
le-
blin
dpl
aceb
oco
ntro
lled
tria
ls.
Wal
ach
H,
Mol
linge
rH
,S
herr
J,S
chne
ider
R.
JP
sych
opha
rmac
ol.
2008
Jul;2
2(5)
:543
–52.
PM
ID:
1870
1641
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
We
cond
ucte
dtw
opa
ralle
l,bl
inde
dho
meo
path
icpa
tho-
gene
tictr
ials
cond
ucte
dat
two
diff
eren
tsi
tes
tode
term
ine
whe
ther
sym
ptom
sre
port
edby
heal
thy
volu
ntee
rsw
ere
sign
ifica
ntly
diff
eren
tfo
rho
meo
path
icre
med
ies
than
for
plac
ebos
.S
tudy
1us
eda
two-
arm
edde
sign
,te
stin
goz
one
agai
nst
plac
ebo.
Stu
dy2
used
ath
ree-
arm
edde
sign
,tes
ting
ozon
ean
dir
idiu
mag
ains
tpl
aceb
o.
No
The
role
ofa
hom
oeop
athi
cpr
epar
-at
ion
com
pare
dw
ithco
nven
tiona
lth
erap
yin
the
trea
tmen
tof
inju
ries
:an
obse
rvat
iona
lco
hort
stud
y.
Sch
neid
erC
,Sch
neid
erB
,H
anis
chJ,
van
Has
elen
R.
Com
plem
ent
Ther
Med
.20
08Fe
b;16
(1):2
2–7.
Epub
2007
Jul
12.
PM
ID:
1834
6625
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
Mul
ti-ce
ntre
,pr
ospe
ctiv
e,co
mpa
rativ
eob
serv
atio
nal
coho
rtst
udy
ofpa
tient
sw
ithva
riou
sm
uscu
losk
elet
alin
ju-
ries
.G
erm
anph
ysic
ians
who
wer
eus
ing
hom
eopa
thy
inad
ditio
nto
conv
entio
nal
med
icin
ein
clud
edpa
tient
s.P
atie
nts
trea
ted
with
Trau
mee
lw
ere
com
pare
dw
ithpa
tient
sm
anag
edco
nven
tiona
lly.
The
prim
ary
outc
ome
mea
sure
was
the
rate
ofre
solu
tion
ofth
epr
inci
pal
sym
p-to
ms
(i.e.
pain
and
infla
mm
ator
ysy
mpt
oms)
atth
een
dof
ther
apy.
No
beca
use
ther
eco
uld
bea
plac
ebo
effe
ctin
both
grou
psso
ther
eis
noco
ntro
lfo
rpl
aceb
o
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 15
Tabl
e1.
Con
tinu
ed.
Title
Aut
hors
and
refe
renc
eTr
ial
desi
gnN
on-t
reat
men
tgr
oup
used
asa
com
pari
son
Effe
ctof
hom
eopa
thy
onan
alge
sic
inta
kefo
llow
ing
knee
ligam
ent
reco
n-st
ruct
ion:
aph
ase
III
mon
ocen
tre
ran-
dom
ized
plac
ebo
cont
rolle
dst
udy.
Par
isA
,G
onne
tN
,C
haus
sard
C,
Bel
onP,
Roc
ourt
F,S
arag
aglia
D,
Cra
cow
ski
JL.
Br
JC
linP
harm
acol
.20
08Fe
b;65
(2):1
80–7
.P
MID
:18
2517
57[P
ubM
ed–
inde
xed
for
MED
LIN
E]
This
was
anad
d-on
rand
omiz
edco
ntro
lled
stud
yw
ithth
ree
para
llelg
roup
s:a
doub
le-b
lind
hom
eopa
thic
orpl
aceb
oar
man
dan
open
-lab
elno
nint
erve
ntio
nal
cont
rol
arm
.El
igib
lepa
tient
sw
ere
18–6
0ye
ars
old
cand
idat
esfo
rsu
rger
yof
the
ante
rior
cruc
iate
ligam
ent.
Trea
tmen
tw
asad
min
iste
red
the
even
ing
befo
resu
rger
yan
dco
ntin
ued
for
thre
eda
ys.
The
prim
ary
end-
poin
twas
cum
ulat
edm
orph
ine
inta
kede
liver
edby
PC
Adu
ring
the
first
24h
infe
rior
orsu
peri
or/e
qual
to10
mg
day(�
1).
Yes
The
effe
ctof
addi
ngho
meo
path
ictr
eatm
ent
tore
habi
litat
ion
onm
uscl
eto
neof
child
ren
with
spas
ticce
rebr
alpa
lsy.
Saj
edi
F,A
lizad
V,A
laed
dini
F,Fa
tem
iR
,M
azah
erin
ezha
dA
.C
ompl
emen
tTh
erC
linP
ract
.20
08Fe
b;14
(1):3
3–7.
Epub
2007
Dec
27.
PM
ID:
1824
3940
[Pub
Med
–in
dexe
dfo
rM
EDLI
NE]
This
stud
yw
asa
doub
le-b
lind
clin
ical
tria
l.Tw
enty
-fou
rsu
bjec
tsw
ere
recr
uite
dfr
oma
deve
lopm
enta
ldi
sord
ers
clin
icin
Tehr
anin
2004
.Sub
ject
sw
ere
divi
ded
into
case
and
cont
rol
grou
ps.
The
rout
ine
reha
bilit
atio
nte
chni
ques
wer
eca
rrie
dou
tfo
rfo
urm
onth
son
both
the
grou
ps.T
heco
ntro
lgr
oup
rece
ived
plac
ebo
and
the
case
grou
pre
ceiv
edho
m-
eopa
thy
drug
s.B
oth
grou
psw
ere
eval
uate
dan
dco
mpa
red
for
mus
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tone
befo
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onth
saf
ter
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ing
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Mod
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Ash
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Trea
ting
hot
flush
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sal
wom
enw
ithho
meo
path
ictr
eatm
ent
–re
sults
ofan
obse
rvat
iona
lst
udy.
Bor
det
MF,
Col
asA
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arijn
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Mas
son
J,Tr
icha
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.H
omeo
path
y.20
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n;97
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inde
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Ope
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mat
ican
dno
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para
tive
obse
rvat
iona
lst
udy
ofho
meo
path
ictr
eatm
ents
pres
crib
edan
dth
eir
effe
ctiv
enes
s,ob
serv
ing
thei
rim
pact
onqu
ality
oflif
e.
No
Hom
otox
icol
ogic
alre
med
ies
vers
usde
smop
ress
inve
rsus
plac
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inth
etr
eatm
ent
ofen
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-blin
d,co
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ara
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man
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icol
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A,
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lini
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ub20
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The
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hom
otox
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ies
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P)
inth
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ent
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atic
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NE)
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ted
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oubl
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le-d
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lin
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ndom
lyas
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edto
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ive
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otox
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alre
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dDA
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No
Filte
rsactivate
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inth
ela
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years
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linic
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nim
aland
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ntstu
die
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stu
die
sbased
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tionnaire
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cebo
contr
olled
tria
loccurr
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Journal of the Royal Society of Medicine Short Reports
16 J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927
Tabl
e2.
Pub
Med
sear
chfo
r‘h
omeo
path
y’þ
‘spe
cifi
c’.
No.
Title
ofst
udy
Aut
hor
Sou
rce
1M
ultiw
eek
rest
ing
EEG
cord
ance
chan
gepa
tter
nsfr
omre
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edol
fac-
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nw
ithtw
oco
nstit
utio
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salie
ntho
meo
path
icre
med
ies
inhe
alth
yyo
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adul
ts
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ower
ter
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Jack
son
N,
Bro
oks
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war
tzG
E.S
ourc
eD
epar
tmen
tof
Fam
ily&
Com
mun
ityM
edic
ine,
The
Uni
vers
ityof
Ari
zona
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olle
geof
Med
icin
e,Tu
cson
,A
Z85
719,
US
A.
ibel
l@em
ail.a
rizo
na.e
du
JA
ltern
Com
plem
ent
Med
.20
12M
ay;1
8(5)
:445
–53.
doi:
10.1
089/
acm
.201
1.09
31
2S
hort
-ter
mef
fect
sof
repe
ated
olfa
ctor
yad
min
istr
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nof
hom
eopa
thic
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hur
orpu
lsat
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ectr
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epha
lo-
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alph
apo
wer
inhe
alth
yyo
ung
adul
ts
Bel
lIR
,B
rook
sA
J,H
ower
ter
A,
Jack
son
N,
Sch
war
tzG
E.S
ourc
eD
epar
tmen
tof
Fam
ily&
Com
mun
ityM
edic
ine,
The
Uni
vers
ityof
Ari
zona
Col
lege
ofM
edic
ine,
1450
NC
herr
yA
venu
e,Tu
cson
,A
Z85
719,
US
A.
ibel
l@em
ail.a
rizo
na.e
du
Hom
eopa
thy.
2011
Oct
;100
(4):2
03–1
1.do
i:10
.101
6/j.h
omp.
2011
.06.
005.
3H
omeo
path
yfo
rde
pres
sion
–D
EP-
HO
M:
stud
ypr
otoc
olfo
ra
rand
omiz
ed,
part
ially
doub
le-b
lind,
plac
ebo
con-
trol
led,
four
arm
edst
udy.
Adl
erU
C,
Kru
ger
S,
Teut
M,
Ludt
keR
,B
arts
chI,
Sch
utzl
erL,
Mel
cher
F,W
illic
hS
N,
Lind
eK
,W
ittC
M.
Sou
rce
Inst
itute
for
Soc
ial
Med
icin
e,Ep
idem
iolo
gyan
dH
ealth
Econ
omic
s;C
hari
teU
nive
rsity
Med
ical
Cen
ter;
D-1
0098
Ber
lin,
Ger
man
y.ub
irat
an.a
dler
@ch
arite
.de
Tria
ls.
2011
Feb
14;1
2(1)
:43.
doi:
10.1
186/
1745
-621
5-12
-43.
4P
roto
col
for
aph
ase
1ho
meo
path
icdr
ugpr
ovin
gtr
ial.
Inst
itute
for
Soc
ial
Med
icin
e,Ep
idem
iolo
gyan
dH
ealth
Econ
omic
s,C
hari
teU
nive
rsity
Med
ical
Cen
ter,
Ber
lin,
Ger
man
y.m
icha
el.te
ut@
char
ite.d
e
Tria
ls.
2010
Jul
22;1
1:80
.do
i:10
.118
6/17
45-6
215-
11-8
0.
5H
omeo
path
ictr
eatm
ent
ofpa
tient
sw
ithm
igra
ine:
apr
ospe
ctiv
eob
serv
atio
nal
stud
yw
itha
2-ye
arfo
llow
-up
peri
od.
Witt
CM
,Lu
dtke
R,
Will
ich
SN
.S
ourc
eIn
stitu
tefo
rS
ocia
lM
edic
ine,
Epid
emio
logy
and
Hea
lthEc
onom
ics,
Cha
rite
Uni
vers
ityM
edic
alC
ente
r,B
erlin
,G
erm
any.
clau
dia.
witt
@ch
arite
.de
JA
ltern
Com
plem
ent
Med
.20
10A
pr;1
6(4)
:347
–55.
doi:
10.1
089/
acm
.200
9.03
76.
6H
omeo
path
icpa
thog
enet
ictr
ials
pro-
duce
spec
ific
sym
ptom
sdi
ffer
ent
from
plac
ebo.
Mol
linge
rH
,S
chne
ider
R,
Wal
ach
H.
Sou
rce
Dep
artm
ent
ofH
uman
Sci
ence
s,U
nive
rsity
ofO
snab
ruck
,G
erm
any.
Fors
chK
ompl
emen
tmed
.20
09A
pr;1
6(2)
:105
–10.
doi:
10.1
159/
0002
0938
6.Ep
ub20
09A
pr9.
7D
iscl
osur
eto
phys
icia
nsof
CA
Mus
eby
brea
stca
ncer
patie
nts:
findi
ngs
from
the
Wom
en’s
Hea
lthy
Eatin
gan
dLi
ving
Stu
dy.
Dep
artm
ent
ofFa
mily
and
Pre
vent
ive
Med
icin
e,M
oore
sU
CS
DC
ance
rC
ente
r,C
ance
rP
reve
ntio
nan
dC
ontr
ol,
Uni
vers
ityof
Cal
iforn
iaS
anD
iego
,La
Jolla
,C
A92
093-
0901
,U
SA
.gs
axe@
ucsd
.edu
Inte
grC
ance
rTh
er.
2008
Sep
;7(3
):122
–9.
(continued)
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 17
parameter was the number of remedy-specific
symptoms per group. They concluded that
homeopathic remedies do produce different
symptoms from placebo.
The specific effects of the homeopathic consult-
ation itself have been examined by Brien et al.25
who conducted a double-blind, randomized pla-
cebo-controlled trial in patients with active stable
rheumatoid arthritis (RA). They concluded that
the impact of the homeopathic consultation is of
clinical relevance to patients and clinicians and
that a further study would be justified.
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hom
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159/
0001
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5.Ep
ub20
08A
ug15
.
9H
omeo
path
icpa
thog
enet
ictr
ials
pro-
duce
mor
esp
ecifi
cth
anno
n-sp
ecifi
csy
mpt
oms:
resu
ltsfr
omtw
odo
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� 2013 The Author(s)
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non-commercial use, distribution and reproduction in any medium, provided the original work is
properly cited.
An exploration of the relationship between placebo and homeopathy
J R Soc Med Sh Rep 2013: 4: 1–19. DOI: 10.1177/2042533313490927 19