Evidence for the efficacy of complementary and
alternative medicines in the management of
fibromyalgia: a systematic review
Vijitha De Silva1,2, Ashraf El-Metwally1, Edzard Ernst3, George Lewith4and Gary
J. Macfarlane1, on behalf of the Arthritis Research Campaign working group on
complementary and alternative medicines*
Objective. To critically evaluate the evidence regarding complementary and alternative medicines (CAMs)
taken orally or applied topically for the treatment of FM.
Methods. Randomized controlled trials of FM using CAMs, in comparison with other treatments or
placebo, published in English up to March 2009, were eligible for inclusion. They were identified using
systematic searches of bibliographic databases and manual searching of reference lists. Information was
extracted on outcomes, and statistical significance, in comparison with alternative treatment or placebo,
and side effects were reported. The methodological quality of the primary studies was determined.
Results. Single studies on four CAMs, and three on different approaches to homeopathic care were
identified. Their methodological quality was moderate. The homeopathy studies were small, but each
reported an improvement in pain. The effects of anthocyanidins, capsaicin and S-adenosylmethionine
each showed at least one statistically significant improved outcome compared with placebo. However,
the studies of anthocyanidins and capsaicin only demonstrated an improvement in a single outcome,
sleep disturbance and tenderness, respectively, of several outcomes considered. No evidence of efficacy
was found regarding Soy in a single study. Most of these CAMs were free of major adverse effects and
usually associated with only minor adverse effects such as dizziness, nausea and stomach upsets.
Conclusion. There is insufficient evidence on any CAM, taken orally or applied topically, for FM. The small
number of positive studies lack replication. Further high-quality trials are necessary to determine whether
these initial findings can be supported by a larger evidence base.
words: Fibromyalgia,Complementaryandalternativemedicine,Anthocyanidins, Capsaicin,Soy,
FM is a chronic, generalized pain syndrome that affects
the musculoskeletal system. It is characterized by
widespread pain, the presence of multiple tender points,
fatigue and sleep disturbances without any structural or
inflammatory cause . It is a common problem among
the attendeesto rheumatology clinics
amounts to 10–20% of new visits . In 1990, the ACR
proposed classification criteria for FM: these required
chronic widespread pain, i.e. pain on both sides, upper
and lower parts of the body and in the axial skeleton for at
least 3 months, and presence of tenderness at 11 or more
1Aberdeen Pain Research Collaboration (Epidemiology Group), School
of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK,
2Department of Community Medicine, University of Ruhuna, Sri Lanka,
3Complementary Medicine, Peninsula Medical School, University of
Exeter, Exeter and4Complementary and Integrated Medicine
Research Unit, University of Southampton, Southampton, UK.
Correspondence to: Gary J. Macfarlane, Epidemiology Group, School
of Medicine and Dentistry, University of Aberdeen, Polwarth Building
(Room 1:068), Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
*See Appendix 1 for the members of the Arthritis Research Campaign
working group on complementary and alternative medicines.
Submitted 28 September 2009; revised version accepted
13 January 2010.
! The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org
Advance Access publication 3 March 2010
SCIENCE by guest on December 23, 2015
of 18 specific sites . Prevalence in the general popula-
tion has been reported as 2% in the USA and 3.3% in
Canada and 0.7% in Denmark and Sweden [2, 4–6].
Studies consistently demonstrate a female predominance
of the disease [2, 4–6] and show that FM is more frequent
in older age and with lower levels of education .
A large number of different therapies for FM have
Rheumatism (EULAR) has reviewed the available evidence
and published guidelines for the treatment of FM in 2008
. This guideline consists of nine specific recommenda-
Due to the chronic nature of the disease, its effects on
quality of life, and the fact that most treatments will result
only in modest improvement in symptoms and function,
patients commonly try alternative methods of treatment
. These treatment methods are commonly categorized
as complementary and alternative medicines (CAMs). The
World Health Organization has defined CAM as ‘A broad
set of health care practices that are not part of the coun-
try’s own tradition and are not integrated into the domi-
nant healthcare system’ . Usage of CAM seems to be
increasing in industrialized countries . In the UK, for
example, 46% of people use CAM during their lifetime and
about 10% of the population will visit a complementary
medical practitioner each year .
CAM is most popular among patients who are suffer-
ing from diseases for which conventional therapies
have failed to offer a cure or satisfactory control .
Rheumatological problems are among the commonest
disease conditions encountered by CAM practitioners
with around four in five of their consultations related to
rheumatological conditions . For FM patients, CAM
usage can be close to 100% [14, 15].
Given this popularity, it is important that patients and
practitioners have accessible and clear evaluation of the
efficacy and safety of these treatments. The purpose of
the review is to summarize and critically evaluate the evi-
dence from randomized controlled trials (RCTs) regarding
CAMs taken orally or applied topically for the treatment of
FM. We have ensured that, where possible, we report
the conduct and results of the review according to the
recently published guidelines on Transparent Reporting
of Systematic Reviews and Meta-Analyses (PRISMA;
The following criteria were used to select the articles:
(i) the study was an RCT involving a CAM; (ii) the route
of administration was oral or topical; (iii) comparison was
made with placebo or other treatment; (iv) a complemen-
tary medicine substance was available in the UK;
(v) involved human subjects with FM; (vi) the study used
recognized criteria for FM; and (vii) the study was pub-
lished in English. Publications up until the end of March
2009 were included in the review.
Publications included in the present review were retrieved
using computerized searches of the following databases:
EMBASE (1980 to March 2009), Ovid MEDLINE (1950 to
March 2009), Allied and Complementary Medicine (1985
to March 2009), EBM Reviews—ACP Journal Club (1991
to March2009),EBM Reviews—Cochrane
Register of Controlled Trials (First Quarter 2009), EBM
Reviews—Cochrane Database of Systematic Reviews
(First Quarter 2009) and EBM Reviews—Database of
Abstracts of Reviews of Effects (First Quarter 2009).
Two hundred and eighteen names of complementary
medicinal substances that are commonly used in rheu-
matic diseases and the key words: alternative medicine,
controlled) trials, (systematic) reviews and meta-analysis
were used in the search.
Two reviewers independently screened the titles of the
selected articles and excluded duplicates and those
obviously irrelevant. Abstracts of the selected articles
were examined independently by two reviewers who
applied the selection criteria. If the information in the
abstracts was insufficient to make a decision, full papers
were retrieved and used for this purpose. The references
of all selected relevant articles including systematic
reviews and meta-analysis were manually searched to
obtain additional relevant publications. During consensus
meetings, disagreements of selections were resolved.
Dataextraction and items
Data were extracted by a single reviewer and checked by
a second reviewer. Data extracted were: CAMs under
investigation, number of persons recruited to the trial,
length of follow-up, outcome measurements studied,
data on statistical significance of change of CAM treat-
ment in relation to the comparator and side effects
reported. The 5-point Jadad scoring system was used
to assess the methodological quality of the selected
trials with increasing score indicating a higher quality of
A total of 60 citations were identified through our
searches. From these, 38 were excluded by examination
of their titles. Excluded studies were mainly duplicates,
studies on rheumatic diseases other than FM, study
designs other than RCTs, studies on fractures, studies
of other forms of complementary medicine such as acu-
puncture and massage, studies on animals and studies
published in languages other than English. Abstracts of
the remaining 22 articles and studies identified by the
screening of references of relevant original and review
articles were scrutinized by the two reviewers. From this
Vijitha De Silva et al.
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process, a total of seven RCTs were included in the
review. The process of identifying relevant studies is
detailed in Fig. 1.
Studycharacteristics and results
There were single RCTs identified for four CAMs used in
FM and three RCTs concerning different approaches to
homeopathic care (Table 1).
Anthocyanidins. This is a food supplement that belongs
to the flavonoid group of plant-derived chemicals. It has
been commonly used for the treatment of chronic dis-
eases. We found one RCT that tested the efficacy of
anthocyanidins in the treatment of FM compared with a
placebo group. The product used in this study is available
in the UKunderthe trade
Anthocyanidins in this product were derived from grape
seeds, bilberries and cranberries. Only 12 patients parti-
cipated in a cross-over study, where all patients received
four different treatments in sequence. The order of
assignment to treatment was randomly determined:
anthocyanidins 120, 80 and 40mg/day or an indistinguish-
able placebo capsule. The total trial period was 52 weeks
with each treatment given for 12 weeks, preceded by a
4-week baseline period. There were no wash-out periods
between treatments. Pain, fatigue and sleep disturbances
were measured as the outcomes, and all were recorded
using a 5-point scale: for pain and fatigue, from ’no
symptoms’ to ‘very severe symptoms’ and for sleep,
from ‘sleep well all night’ to ‘sleep very severely affected
by FM’. Only sleep disturbance was significantly improved
by active treatment. The largest improvement was
observed with the dose of 80mg/day (P = 0.004). No
significant improvements were observed in pain or fatigue
scores. Minor adverse effects such as indigestion, nausea
and sinusitis were reported .
Capsaicin. This is a herbal medicinal extract from chili
peppers. One RCT tested the efficacy of the local appli-
cation of 0.025% capsaicin in the treatment of FM com-
pared with a placebo cream. The product used in this
study is available under the trade name of Zostrix.
Forty-five patients were randomly assigned to one of the
four groups: (i) right side, 0.025% capsaicin; left side, con-
trol; (ii) right, placebo; left, control; (iii) right, control; left,
0.025% capsaicin; and (iv) right, control; left, placebo.
After 4 weeks of double-blind treatment, patients were
reassessed for pain, tenderness and quality of sleep.
Pain and quality of sleep were assessed using a visual
analogue scale (VAS), whereas tenderness was measured
FIG. 1 Process of selecting articles for inclusion in the review.
Computerized search of
databases: 60 citations
Twenty-two abstracts and (if
necessary) full papers were read
by two reviewers independently
Five full papers identified as
Two additional full papers
identified as eligible
or unrelated to the
included in review
CAM in management of FM
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using a dolorimeter. Significant improvement of tender-
ness was associated with capsaicin. However, there
was no improvement in pain or quality of sleep.
Transient stinging or burning at the application sites
were reported as adverse effects. Due to the burning
effect of capsaicin on the skin, it is questionable whether
this trial was double-blind .
Soy. The efficacy of this commonly used dietary supple-
ment has been tested in one RCT. Fifty patients were
randomly assigned to receive either Soy or placebo
shakes (casein) once a day for a period of 6 weeks.
Questionnaire (FIQ) and the Centre of Epidemiologic
Studies Depression (CES-D) scale at baseline and after
6 weeks of treatment. There was no statistically significant
benefit of Soy compared with placebo. No adverse effects
were reported .
S-adenosylmethionine. The chemical compound of this
nutritional supplement is derived from two acids: methio-
nine,an amino acid, and
a nucleic acid. One RCT compared the efficacy of
S-adenosylmethionine (SAMe) with placebo. Forty-four
patients with FM were randomly assigned to receive
either SAMe 400mg tablet or identical placebo tablets
twice a day for a period of 6 weeks. Pain, fatigue, quality
of sleep and clinical disease activity were measured using
a VAS. After the treatment, significant improvements were
observed in pain experienced during the last week
(P=0.002), clinical disease activity (P=0.04), morning
stiffness (P=0.03), fatigue (P=0.02) and mood evaluated
by face scale (P=0.006) among the SAMe-treated
patients compared with the placebo group. However,
there was no significant difference in tender point score,
mood (evaluated by the Beck Depression Inventory) or
isokinetic muscle strength. Mild adverse effects such as
stomach upset and dizziness were reported .
Homeopathy. Three RCTs compared the efficacy, against
placebo, of three different homeopathic approaches. In
the first trial, 30 patients were randomly assigned to
receive either Rhus toxicodendron (6c potency) put up
on 125mg lactose or identical placebo tablets three
times per day . This was a cross-over study with treat-
ment phases of 1 month each in random sequence.
Patients receiving the active treatment had significantly
fewer tender points (P<0.005), improved pain and sleep
(P<0.005), as assessed by VAS. Only patients in whom
‘Rhus toxicodendron was positively indicated after a
homeopathic consultation’ were included in this trial. In
the second trial, 24 patients were allocated to receive
one remedy from Arnica montana, Bryonia alba and R.
toxicodendron (all of 6c potency) based on a homeopathic
consultation or a matching placebo . All the patients
received the same treatment throughout a 3-month
period. Homeopathic treatments significantly improved
pain (P<0.05) and sleep (P<0.05) compared with pla-
cebo as assessed by VAS. This study received the
lowest quality score. In the third trial, 62 patients were
TABLE 1 RCTs of CAMs in the treatment of FM
Outcome of the study in CAM
treatment vs comparison group
Edwards et al. 
Pain, fatigue, sleep
Significant improvement in sleep
McCarty et al. 
Capsaicin topical application
Pain, tenderness quality of
Significant improvement in tenderness
Wahner-Roedler et al. 
Soy dietary supplement
Scores of FIQ and CES-D
No significant difference in outcome
Jacobsen et al. 
Tenderness, pain, fatigue,
morning stiffness, mood,
clinical disease activity,
tender point score, muscle
Significant improvements in pain, fati-
gue, morning stiffness, mood and
clinical disease activity
Fisher et al. 
Tenderness, pain, sleep
Significant improvement in tenderness,
pain and sleep was observed
Homeopathy (Arnica, Bryonia,
Significant improvement in pain and
Bell et al. 
Tenderness, tender point pain,
tender point count, quality of
life, global health, depression
Significant improvement in tender point
pain, tender point count, quality of life
and global health and depression
Vijitha De Silva et al.
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randomly assigned to receive either an individually
selected homeopathic remedy or placebo . In this
Questionnaire , quality of life was assessed using
the FM quality of life scale  and global health was
assessed using a global self-rated health scale .
After 4 months of treatment, patients who received
homeopathic remedies demonstrated significantly better
improvements in tender point pain, tender point count,
quality of life, global health and depression compared
with patients who received placebo. This study received
the highest quality score. Allergic reactions were reported
as adverse effects.
The present review was carried out to determine the
efficacy of CAMs in treating FM using the available evi-
dence in the form of published RCTs. The review was
limited to CAMs that were used orally or topically. The
major finding of the review is that there is little evidence
available to permit firm conclusions about the efficacy of
any CAM in the treatment of FM.
There was some evidence from three small studies
regarding three different homeopathic approaches. Each
demonstrated an improvement in pain in those receiving
the standardized or individualized homeopathic remedy
(compared with placebo) and two studies demonstrated
improvement in sleep. While one of these trials received
the lowest of all Jadad scores , another received the
maximum score . The third study  has been
independently re-analysed and ‘no firm support for the
efficacy of homeopathic treatment’ was found .
The effects of anthocyanidins, capsaicin and SAMe
have only been reported in a single study, each of
which showed some positive results. However, studies
of anthocyanidins and capsaicin only demonstrated an
improvement in a single outcome, sleep disturbance
and tenderness, respectively, of several outcomes con-
sidered. No evidence of efficacy was found regarding
Soy in a single study. Most of these CAM compounds
were free of major adverse effects; minor effects reported
Capsaicin cream was associated with transient stinging
or burning at the application sites.
Interpretation and utilization of the above evidence, in
practice, must be carried out with caution given some
methodological concerns: there is insufficient evidence
base for any compound; evidence regarding all CAMs
except homeopathy are based on a single trial; and
most of the trials were carried out using a small number
of patients. According to the Jadad quality scoring
system, the median score was 3, indicating that the
trials were of moderate quality. Moreover, each of the
homeopathy trials used different remedies. Thus all of
these studies await independent replication. All of the
RCTs included in this review had small sample sizes.
Our review has several important limitations. Publication
bias is a major concern in the interpretation since each of
these compounds may have had other (unpublished) eval-
uations—given that the trials that show no effect are less
likely to be published, it would only take a very small
number of such unpublished null trials to outweigh the
positive results shown for some compounds. We have
selected only RCTs published in the English language
for the present review. Therefore, we may have missed
some evidence on CAM products published in other
languages. In the search conducted as part of this
review, however, only two studies were rejected because
they were not available in English. Finally, although we
have considered the therapies on an individual basis,
this may not reflect the reality of how CAMs are commonly
used or prescribed. Nevertheless, before consideration of
the more complex question of the efficacy of combination
of therapies, it is reasonable to consider whether there is
any evidence that these approaches are efficacious
Future research in this area should overcome the meth-
odological flaws of the current data. In particular, sample
sizes should be calculated based on the reliable pilot data,
treatment periods should be long enough for a therapeutic
effect to show, cross-over studies should include a
wash-out period and trial reporting should follow the
Consolidated Standardsof ReportingTrialsguidelines .
Although CAM is highly popular among FM patients, this
review failed to find any RCT for many CAM compounds
that are frequently used in its treatment. Even for those
studied in RCTs, there is insufficient evidence for any
single compound to make a conclusion on efficacy.
Further methodologically robust trials are warranted to
extend the evidence base.
Rheumatology key messages
. Most CAMs (taken orally or applied topically) for FM
do not have any evidence available on their efficacy
. Of those tested in RCTs, there is insufficient
evidence of efficacy for any single CAM.
One employee of the ARC (J. Tadman, press officer) was a
member of the working party. This manuscript provides
the detailed methods and results behind the ARC report
‘Complementary and alternative medicines for the treat-
ment of rheumatoid arthritis, osteoarthritis and fibromyal-
gia’ (www.arc.org.uk). We thank Kate Boddy for her help
in undertaking the database searches. P.V.deS. under-
took this work while on secondment to the University of
Funding: This work was funded by the Arthritis Research
Campaign (ARC), Chesterfield, UK.
CAM in management of FM
by guest on December 23, 2015
Disclosure statement: The authors have declared no con- Download full-text
flicts of interest.
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Arthritis Research Campaign working party on CAMs:
Prof. Howard Bird (University of Leeds), Prof. Janet
Cade (University of Leeds), Prof. Edzard Ernst (University
of Exeter), Ms Jane Feinmann (Medical Writer), Mrs
Margaret Fisken (Patient Representative), Prof. George
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(Aberdeen Royal Infirmary)
(Arthritis Research Campaign Press Officer).
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