PLOS ONE | DOI:10.1371/journal.pone.
0132989 July 15, 2015 1 / 40
OPEN ACCESS
Citation: Tan J-Y, Suen LKP, Wang T, Molassiotis A (2015) Sham Acupressure Controls Used in Randomized Controlled Trials:
A Systematic Review and Critique. PLoS ONE 10(7): e0132989. doi:10.1371/journal.pone.0132989
Editor: Nguyen Tien Huy, Institute of Tropical Medicine (NEKKEN), Nagasaki University, JAPAN
Received: January 22, 2015
Accepted: June 23, 2015
Published: July 15, 2015
Copyright: © 2015 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited.
Data Availability Statement: All relevant data are within the paper and its Supporting Information files.
Funding: These authors have no support or funding to report.
Competing Interests: The authors have declared that no competing interests exist.
RESEARCH ARTICLE Sham Acupressure Controls
Used in Randomized Controlled Trials: A Systematic
Review and Critique
Jing-Yu Tan1,2, Lorna K. P. Suen1, Tao Wang3, Alexander Molassiotis1*
1 School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China, 2 School of
Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China, 3 The Second Affiliated People’s Hospital,
Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
4
[email protected] Abstract
Objectives
To explore the commonly utilized sham acupressure procedures in existing acupressure tri- als, and to assess whether different
types of sham interventions yield different therapeutic outcomes, and, as far as possible, to identify directions for the future
development of an adequate sham acupressure method.
Methods
Randomized controlled trials comparing true acupressure with sham interventions were included. Thirteen electronic databases
were adopted to locate relevant studies from incep- tion to July 3, 2014. Meanwhile, eight Chinese journals on complementary
and alternative medicine were manually searched to locate eligible articles. In addition, eligible studies listed in the reference lists
of the included papers and other related systematic reviews on acupressure were also screened to further search any potentially
eligible trials. Methodolog- ical quality of the included studies was evaluated using the risk of bias assessment tool developed by
the Cochrane Back Review Group. Descriptive analysis was adopted to sum- marize the therapeutic outcomes.
Results
Sixty-six studies with 7265 participants were included. Methodological quality of the included trials was generally satisfactory.
Six types of sham acupressure approaches were identified and “non-acupoint” stimulation was the most frequently utilized sham
point while an acupressure device was the most commonly used approach for administering sham treatments. Acupressure
therapy was a beneficial approach in managing a variety of health problems and the therapeutic effect was found to be more
effective in the true acupressure groups than that in the sham comparative groups. No clear association could be identified
between different sham acupressure modalities and the reported treatment outcomes.
Sham Acupressure Controls Used in Randomized Controlled Trials
Conclusions
A great diversity of sham acupressure controls have been used in clinical practice and research. A solid conclusion whether
different sham alternatives are related to different treatment outcomes cannot be derived because of significant clinical
heterogeneity among the analyzed trials. Non-acupoints are generally recommended but the definite locations should be
identified with caution. For studies using single sham acupoints on hands or legs, it is suggested to apply identical acupressure
devices on the same acupoint as in the active intervention without any stimulation. While for studies on pain, stimulation of sham
acu- points should be avoided.
Introduction
Randomized controlled trial (RCT) is one of the commonly used experimental methods for testing the effectiveness
of an intervention [1]. To distinguish the specific effect of a therapeutic approach from the non-specific effect, a
placebo control is usually employed [2]. Placebo is defined as “any therapy or component of therapy used for its
nonspecific, psychological, or psychophysiological effect, or that is used for its presumed specific effect, but is
without specific activity for the condition being treated” [3] (p. 371). A placebo intervention is commonly used in
experimental drug studies where the “placebo drug” is identical to the active agent without any specific
pharmacological activity against the disease. Theoretically, placebo comparisons should be indistinguishable from
the true intervention, and most importantly, should be inert, which means only create non-specific physiological and
psychological changes [4]. However, an adequate placebo design becomes difficult to implement when a study is
adopting complex non-pharmacological interventions such as physiotherapy, acupuncture or acupressure, etc.
Multiple mechanisms involved in these types of treatments make it complicated to develop an appropriate placebo
control group.
Acupressure has been widely applied in dealing with a variety of health issues globally. In addition to the specific
therapeutic effects, stimulation at the acupoints is also believed to gen- erate some non-specific effects, in both
physiological and psychological aspects [5]. Placebo controls adopted in acupressure trials are usually referred to as
“sham interventions”, which indicate faked acupressure approaches. Various types of sham acupressure have been
reported in the literature which mainly differ in three aspects, the selected acupoints, the acupressure approach, and
the acupressure intensity. Acupoints adopted in sham procedures commonly include non-acupoints, true acupoints as
the active acupressure group, and non-therapeutic acupoints. Non-acupoints generally refer to ineffective body
points which cannot be found on established acupuncture-point charts, while non-therapeutic acupoints means
irrelevant true acupoints considered to be ineffective for the targeted health problem [2,6].
Sham procedures used in acupuncture have received considerable attention in research. A number of RCTs and
systematic reviews have been conducted to investigate the specific treat- ment effect of acupuncture in a wide range
of disorders, especially in pain management, and have yielded contradictory results. Some of them supported the
specific benefit of acupuncture [5,7–9], while others argued that the effects of true acupuncture were similar to that
in the sham intervention [10–12], and consequently reached the conclusion that the so-called treat- ment effect of
acupuncture may be only a non-specific physiological effect and/or a placebo effect. However, before developing
such conclusions, those studies must have a precondition
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 2 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
that the employed sham procedure is inert. Similar situations were also detected in studies of acupressure. Despite
the significant amounts of research on acupressure during the past decades, it is still uncertain which type of sham
acupressure is the most adequate design, and to our knowledge, no study has been conducted so far to summarize the
frequently used sham acupressure modalities and to explore their strengths and drawbacks. Hence, the aims of this
study are to identify the commonly utilized sham procedures in existing acupressure trials, to assess whether
different types of sham intervention yield different therapeutic outcomes, and, if possible, to identify directions for
the future development of an adequate sham acupressure mode.
Methods
This study is a systematic review of the literature (S1 File). A review protocol was created by the first author and it
was approved by two experts with experience in acupressure before the commencement of the study (S2 File).
Data Sources and Search Strategies
Both electronic and manual searches were used to locate relevant studies. Thirteen electronic databases were
accessed including PubMed, EMBase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL,
Allied and Complementary Medicine (AMED), PsycINFO, Thomson Reuters Web of Science, Science Direct,
Foreign Medical Journal Service (FMJS), China National Knowledge Infrastructure (CNKI), WanFang Data,
Chinese Scientific Journal Database (CQVIP) and Chinese Biomedical Literature Database (CBM), from inception
to July 3, 2014. There was no language restriction set for electronic searches. Meanwhile, eight Chinese journals on
complementary and alternative medicine (issues published within the latest three years) were manually searched to
possibly identify some latest publications which were still not included in the online databases. In addition, eligible
studies listed in the reference lists of the included papers and other related systematic reviews on acupressure were
also screened to fur- ther search any potentially eligible trials. Literature searches were performed independently by
two reviewers with Chinese medicine background (JYT and TW). Mesh terms, entry terms, key words and free
words such as “acupressure”, “acupressÔ, “wristbandÔ “shiatsu” and “chih ya” were used in the searching
strategies. Four selected English and Chinese search strategies are listed in S1 Table.
Inclusion and Exclusion Criteria
RCTs comparing true acupressure with a sham intervention were included. Both true and sham acupressure can be
manipulated through either manual intervention or acupressure devices (e.g., wristbands or attached acupressure
beads, etc.). To eliminate the effect of electri- cal stimulation on the therapeutic outcomes of acupressure, studies on
electronic acupressure devices were excluded. At the same time, studies on other modalities of acupuncture-point
stimulation such as manual/electronic/laser acupuncture and moxibustion, as well as all kinds of auricular therapy
were excluded. Studies published in languages other than English and Chi- nese were excluded.
Methodological Quality Evaluation
Methodological quality of the included studies was evaluated using the risk of bias assessment tool developed by the
Cochrane Back Review Group [13]. The tool can be viewed as an exten- sion of the original criteria recommended
by the Cochrane Handbook. It not only includes all
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 3 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
the necessary items described in the latest version of the Cochrane risk of bias tool, but also provides more detailed
criteria for assessing “incomplete outcome data” and “other sources of potential bias”. The tool consists of 12 items
including: (1) “Was the method of randomization adequate?”; (2) “Was the treatment allocation concealed?”; (3)
“Was the patient blinded to the intervention?”; (4) “Was the care provider blinded to the intervention?”; (5) “Was
the outcome assessor blinded to the intervention?”; (6) “Was the drop-out rate described and acceptable?”; (7)
“Were all randomized participants analyzed in the group to which they were allocated?”; (8) “Are reports of the
study free of suggestion of selective outcome reporting?”; (9) “Were the groups similar at baseline regarding the
most important prognostic indicators?”; (10) “Were co-interventions avoided or similar?”; (11) “Was the
compliance acceptable in all groups?” and (12) “Was the timing of the outcome assessment similar in all groups?”
[13]. Each item can be rated as of “yes”, “no” or “unclear” where “yes” indicates a low risk of bias [13].
Importantly, different from the original Cochrane risk of bias criteria, the tool used in this study can provide an
overall methodological quality assessment for a single trial. The overall quality can be assessed as “low risk of bias”
when at least six items are scored as “yes” and no serious method- ological flaws are identified (e.g. 80% dropout
rate found in one study arm) [13]. In this review, only RCTs with low risk of bias were eligible for final analysis.
Data Extraction
For each of the included studies, the following data was extracted independently by the same two reviewers: (1)
study general information (first author, year of publication, full name of journal, country of origin, type of study
design, and study setting); (2) participant characteris- tics (age, gender, sample size, dropout rate, diagnostic criteria,
inclusion and exclusion criteria, and reason for acupressure); (3) true/sham acupressure protocols (practitioner,
acupressure equipment, selected acupoints, treatment duration and number of sessions, and acupressure intensity and
frequency, etc.); (4) main outcome(s) and results of the therapeutic effects; (5) adverse events associated with
acupressure; and (6) assessment of methodological quality (12 items of the risk of bias tool plus examination of the
credibility of blinding). For studies com- prising more than two active treatment arms, only data from true and sham
acupressure arms were extracted for analysis. Meanwhile, for studies including another control group with stan- dard
methods of care, data from the standard care arm were also extracted accordingly. Dis- agreement between the two
reviewers was resolved by discussion or by consulting a third reviewer (AM).
Classification of Sham Acupressure Methods
After going through all of the sham acupressure protocols of the included studies as well as reviewing the sham
control classifications for body and auricular acupuncture in previous studies [2,14,15], sham methods in this study
were classified into six types which are described in Table 1.
Data Analysis
A quantitative synthesis of the main outcomes was originally proposed in the study protocol. However, a precise
meta-analysis was deemed impossible due to the significant clinical hetero- geneity identified in the health
conditions, patient characteristics, intervention protocols and outcome measures among studies. A subgroup
meta-analysis for the same health conditions within each sham acupressure type was also considered but finally
abandoned for the reasons that clinical heterogeneity was still considerable within each sham modality, and the
number of trials in some sham types was insufficient for data synthesis. To provide an exploratory analysis
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 4 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
Table 1. Classification of Sham Acupressure Methods.
Types of Sham
Description Methods
Type 1 Sham Acupressure at Non-acupoints by Manual Pressure Type 2 Sham Acupressure at Non-acupoints by Employing
Acupressure Devices Type 3 Pseudo-intervention at the Same Acupoints as True Treatment Arm by Manual
Light-Touch Type 4 Pseudo-intervention at the Same Acupoints as True Treatment Arm by using
Placebo Devices Type 5 Manual Acupressure at Non-Therapeutic (Irrelevant) Acupoints Type 6 Sham
Acupressure at Non-Therapeutic (Irrelevant) Acupoints by Adopting
Acupressure Devices
doi:10.1371/journal.pone.0132989.t001
of the study outcomes, responder rate and responder rate ratio (responder rate in true acupres- sure group/responder
rate in sham group) for each study presenting dichotomous data were calculated, and a risk ratio (RR) with 95%
confidence interval (CI) was used to present the responder rate ratio. Descriptive analysis was also used to
summarize the therapeutic outcomes of acupressure, for both the overall effect and the subgroup effect by each sham
alternative. The overall assessment was to investigate whether true acupressure is superior to sham com- parisons
while the subgroup analysis was used to assess whether different types of sham meth- ods could induce different
therapeutic effects.
Results of the treatment effect for each main outcome in each individual study were extracted by two reviewers
according to the following vote counts [2]: “++”: true acupressure is significantly better than sham control for the
main outcome; “+”: trend of the main outcome in favor of true acupressure but without statistical significance; “0”:
no difference between true and sham acupressure; “−”:trend of the main outcome in favor of sham acupressure but
with- out statistical significance; and “− −”: sham intervention is significantly better than true acu- pressure for the
main outcome. For studies reporting multiple main outcomes, all such outcomes were included for analysis. For
studies not indicating the main outcomes, all vari- ables with between-group comparison were extracted
accordingly.
In addition, subgroup descriptive analyses for different types of health problems, interven- tion duration and
frequency as well as acupressure intensity were also considered when data were available. Based on the analyzed
trials, length of treatment was categorized into “extremely short-term” (less than one hour), “short-term” (more than
one hour but less than one day), “mid-term” (more than one day but less than one week), and “long-term” (more
than one week). For studies on postoperative issue (e.g. nausea, vomiting and pain, etc.) which employed multiple
assessment time points, postoperative data within the first 24 hours were abstracted for analysis. The chi-square test
was used to assess the difference in dropout rates between the true and sham acupressure arms.
Results Characteristics of the Included Studies
A total of 5225 items were located. Among those 2283 duplicated articles were excluded after screening by the
reference management software NoteExpress. A total of 2694 records were subsequently removed by checking titles
and abstracts. For the remaining 248 items, full-texts were accessed for evaluating eligibility, among which, 160
were further removed because they failed to include a sham control group (n = 92), were conference proceedings (n
= 32), were auricular acupressure studies (n = 11), and were articles published in Arabic/Farsi (n = 21),
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 5 / 40
Fig 1. Flow Chart of Study Selection. CENTRAL: Cochrane Central Register of Controlled Trials, CINAHL: Cumulative Index
to Nursing and Allied Health Literature, AMED: Allied and Complementary Medicine, FMJS: Foreign Medical Journal Service,
CNKI: China National Knowledge Infrastructure, CQVIP: Chinese Scientific Journal Database, CBM: Chinese Biomedical
Literature Database
doi:10.1371/journal.pone.0132989.g001
Sham Acupressure Controls Used in Randomized Controlled Trials
Korean (n = 3) and French (n = 1). The remaining 88 articles were further adopted for method- ological quality
evaluation, of which, 22 with high risk of bias were removed (S2 Table) and 66 studies [16–81] were finally
included for analysis. Fig 1 shows the flow chart of the study selection.
The included studies comprised 7265 subjects, with an average sample size of 110 patients per study. These
studies were published between 1991 and 2015 and were conducted in 18 dif- ferent countries or regions. Of which,
13 studies originated from Iran, 12 from the United States, ten from Taiwan, five from Sweden, four from the United
Kingdom, three from Austria, three from South Korea, three from Canada, two from Italy, two from Ireland, two
from India, and one each from Hong Kong, Denmark, Australia, Turkey, Pakistan, Poland and Norway. More than
half were carried out in hospitals or medical centers. Acupressure was used to deal with a variety of health problems
including nausea and vomiting, labor pain, primary dysme- norrhea, sleep disturbance, postoperative gastrointestinal
dysfunction, and anxiety, etc. Char- acteristics of the included studies can be seen in Table 2.
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 6 / 40
Table 2. Characteristics of the Included Studies.
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Type 1—Sham Acupressure at Non-Acupoints: Manual Acupressure Tang et al. 2014 [16], Pulmonary Wards of A
Medical Center, Taiwan
+1 Not Reported2
Atrian et al. 2013 [17], Dormitories of Kashan University of Medical Sciences, Iran
Cancer-related
Total: 57/
TAG 1: Manual
Fatigue (Tang Fatigue
12, TAG 1:
Acupressure at True
Fatigue Rating Scale) 24/8, TAG
Acupoints, TAG 2: 2: 17/2,
Manual Acupressure at SAG: 16/2
True Acupoints + Essential Oils, SAG: Manual Acupressure at Non-Acupoints
Pain Intensity (VAS) 0 No AEs Found in
the Study
Sehhatie-Shafaie et al. 2013 [18], The Public Hospitals of Ardebil, Iran
Primary
Total: 67/
TAG: Manual Dysmenorrhea
8, TAG:
Acupressure at True 33/6, SAG:
Acupoints, SAG: 34/2
Manual Acupressure at Non-Acupoints
++ Not Reported2
Chao et al. 2013 [19], An Urban Medical Center in Taipei, Taiwan
Labor Pain in
Total: 84/
TAG: Manual
Pain Intensity (Visual Nulliparous
0, TAG:
Acupressure at True
Pain Scale) Women
42/0, SAG:
Acupoints, SAG: 42/0
Manual Acupressure at Non-Acupoints
Not Reported2
McFadden et al. 2012 [20], University of Colorado at Boulder, United States
Postoperative
Total: 66/
TAG: Manual
Frequency of Bowel
++(For Bowel Gastrointestinal
6, TAG:
Acupressure at True
Sounds, Time to the
Sounds, Flatus Function
30, SAG:
Acupoints + Routine
First Flatus Passage
Passage, and 30
Care, SAG: Manual
and Defecation, and
Liquid Intake), + Acupressure at Non-
Time to Oral Liquid
(For Solid Intake Acupoints + Routine
and Solid Intake
and Defecation) Care
0 Not Reported2
Valiee et al. 2012 [21], Surgery Wards, Hospital of Tehran University of Medical Science, Iran
Stress Reduction Total: 109/
TAG: Manual
Stress Responses NR, TAG:
Acupressure at True
(Heart Rate, Heart 39/NR,
Acupoints, SAG:
Rate Variability, Skin SAG: 40/
Manual Acupressure at
Conductance NR,
Non-Acupoints, CG: An
Response, State CG:30/NR
Audio Relaxation CD
Anxiety Inventory, and Psychological Stress Measure)
Not Reported2
Rad et al. 2012 [22], Rouhani Hospital of Babol University of Medical Science, Iran
Preoperative
Total: 70/
TAG: Manual
Preoperative Anxiety
++ (For Anxiety, Anxiety
0, TAG:
Acupressure at True
(VAS), and Vital
Respiratory Rate, 35/0, SAG:
Acupoints, SAG:
Signs (Blood
and Systolic Blood 35/0
Manual Acupressure at
Pressure, Heart Rate,
Pressure), + (For Non-Acupoints
and Respiratory Rate)
Heart Rate and Diastolic Blood Pressure) ++ No AEs Found in
the Study
Chang et al. 2011 [23], A Urogynecology Clinic of Queen Elizabeth Hospital, Hong Kong
Nausea and
Total: 85/
TAG: Manual
Intensity of Nausea Vomiting in
5, TAG:
Acupressure at True
(VAS) and Vomiting Pregnancy
43/3, SAG:
Acupoints, SAG:
(Frequency of 42/2
Manual Acupressure at
Vomiting) Non-Acupoints Urodynamic Stress
Total: 81/
TAG: Manual
Pelvic Muscle
++, TAG was
Not Reported2
Incontinence
4, TAG:
Acupressure at True
Strength
Significantly Better 27/1, SAG:
Acupoints + Pelvic Floor
(Perineometry
than SAG and CG; 27/1, CG:
Muscle Training, SAG:
through Measuring
No Difference was 27/2
Manual Acupressure at
Vaginal Squeeze
Found between Non-Acupoints + Pelvic
Pressure)
SAG and CG Floor Muscle Training, CG: Pelvic Floor Muscle Training
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 7 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
McFadden et al. 2011 [24], A Community in Colorado, United States
++ Not Reported2
Kashefi et al. 2011 [25], Bojnoord University of Medical Science, Iran
Traumatic Brain
Total: 42/
TAG: Manual
Cognitive Impairment Injury
0, TAG:
Acupressure at True
and State of Being 21/0, SAG:
Acupoints, SAG:
following Traumatic 21/0
Manual Acupressure at
Brain Injury Non-Acupoints
++ No AEs Found in
the Study
Reza et al. 2010 [26], Kahrizak Charity Nursing Home, Iran
Women’s General
Total: 86/
TAG: Manual
Women’s General Health
10, TAG:
Acupressure at True
Health (General 43/6, SAG:
Acupoints, SAG:
Health Questionnaire) 43/4
Manual Acupressure at Non-Acupoints
Not Reported2
McFadden & Hernández 2010 [27], Denver/Boulder Community in Colorado, United States
Sleep
Total: 90/
TAG: Manual
Self-Reported Sleep
++, TAG was Disturbances
13, TAG:
Acupressure at True
Habits (Pittsburgh
Significantly Better 30/5, SAG:
Acupoints + Usual
Sleep Quality Index)
than SAG and CG; 30/4, CG:
Care, SAG: Manual
The Sleep Quality 30/4
Acupressure at Non-
in SAG was Better Acupoints + Usual
than That in CG but Care, CG: Usual Care
There was no Statistical Significance
Not Reported2
Maa et al. 2007 [28], Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taiwan
Cardiovascular
Total: 16/
TAG: Manual
Heart Rate and Blood
++ (For Heart Function in Stroke
3, TAG: 7/
Acupressure at True
Pressure
Rate), 0 (For Blood Survivors
1, SAG: 9/
Acupoints, SAG:
Pressure) 2
Manual Acupressure at Non-Acupoints
Not Reported2
Shin et al. 2007 [29], Two General Hospitals, South Korea
Symptoms and
Total: 49/
TAG: Manual
Daily Sputum
0, TAG was Better Health-Related
14, TAG:
Acupressure at True
Amounts, Efforts to
than CG Regarding Quality of Life in
16/5, SAG:
Acupoints + Standard
clean Secretions
to the SGRQ Bronchiectasis
17/6, CG:
Care, SAG: Manual
(Sputum Self-
Activity Domain, Patients
16/3
Acupressure at Non-
Assessment), Six-
and SAG was better Acupoints + Standard
Minute Walking
than CG in the Care, CG: Standard
Distance, Breathing
Improvement of Care
Difficulty, and Quality
Sputum Self- of Life (SGRQ)
Assessment
Not Reported2
Bertalanffy et al. 2004 [30], Sites of Accident, Austria
Nausea, Vomiting,
Total: 66/
TAG: Manual
Degree of Nausea
++, The Degree of and Ketonuria
NR, TAG:
Acupressure at True
and Vomiting (The
Nausea and Levels in Women
23/NR,
Acupoints + Routine
Rhodes Index of
Vomiting in TAG with Hyperemesis
SAG: 21/
Intravenous Therapy,
Nausea, Vomiting,
was Statistically Gravidarum
NR, CG:
SAG: Manual
and Retching), and
Lower than SAG 22/NR
Acupressure at Non-
Degree of Ketonuria
and CG, and No Acupoints + Routine
Difference was Intravenous Therapy,
Found between CG: Routine
SAG and CG Intravenous Treatment
++ Not Reported2
Chen et al. 2003 [31], A Mid-Taiwan Teaching Hospital, Taiwan
Motion Sickness in
Total: 100/
TAG: Manual
Nausea Intensity Patients with
0, TAG:
Acupressure at True
(VAS) Trauma
50/0, SAG:
Acupoints, SAG: 50/0
Manual Acupressure at Non-Acupoints Gastrointestinal
Total: 41/
TAG: Manual
Gastrointestinal
++ Not Reported2 Motility after
0, TAG:
Acupressure at True
Motility Surgery
21/0, SAG:
Acupoints, SAG:
(Multifunctional 20/0
Manual Acupressure at
Stethoscope) Non-Acupoints
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 8 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Tsay & Chen 2003 [32], Four Dialysis Centers in Major Hospitals in Taipei, Taiwan
Not Reported2
Kober et al. 2002 [33], Sites of Accident, Austria
Sleep Quality Total: 105/
TAG: Manual
Sleep Quality
0, TAG was 7, TAG:
Acupressure at True
(Pittsburgh Sleep
Significantly Better NR, SAG:
Acupoints + Usual
Quality Index)
than CG; No NR, CG:
Care, SAG: Manual
Difference was NR
Acupressure at Non-
Found between Acupoints + Usual
SAG and CG Care, CG: Usual Care
Not Reported2
Belluomini et al. 1994 [34], Department of Obstetrics and Gynecology, California Pacific Medical Center, United States
Pre-Hospital
Total: 60/
TAG: Manual
Pain (VAS), Anxiety
Comparisons Analgesia
0, TAG:
Acupressure at True
(VAS), and Heart
between Groups 19/0, SAG:
Acupoints, SAG:
Rate
were not Performed 20/0, CG:
Manual Acupressure at
(or Not Clearly 21/0
Non-Acupoints, CG: No
Reported) Acupressure
Not Reported2
Type 2—Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices Adib-Hajbaghery & Etri, 2013 [35],
A General Surgical Ward of A University Hospital, Iran
Nausea and
Total: 90/
TAG: Manual
Nausea and Vomiting
++ (For Nausea), + Vomiting in
30, TAG:
Acupressure at True
(The Index of
(For Vomiting) Pregnancy
46/16,
Acupoints, SAG:
Nausea, Vomiting, SAG: 44/
Manual Acupressure at
and Retching) 14
Non-Acupoints
Not Reported2
Alessandrini et al. 2012 [36], Otolaryngology Department, University of Rome “Tor Vergata”, Italy
Postoperative
Total: 70/
TAG: Acupressure at
Severity of Nausea
++ (For Pain), 0 Pain, Nausea, and
0, TAG:
True Acupoints using
and Pain (VAS), and
(For Nausea), NA Vomiting
35/0, SAG:
Acupressure Band,
Severity of Vomiting
(For Vomiting)3 35/0
SAG: Acupressure at
(Frequency of Non-Acupoints using
Vomiting) Acupressure Band
Not Reported2
Soltani et al. 2011 [37], Farabi Hospital, Iran
Acute Vertigo Total: 204/
TAG: Acupressure at
Severity of Vertigo
Comparisons 0, TAG:
True Acupoints using
and Neurovegetative
between Groups 102/0,
Acupressure Band,
Symptoms (VAS)
were not Performed SAG: 102/
SAG: Acupressure at
(or Not Clearly 0
Non-Acupoints using
Reported) Acupressure Band Postoperative
Total: 200/
TAG: Using
Postoperative
++4 Not Reported2 Nausea and
0, TAG:
Acupressure Wrist Band
Nausea and Vomiting Vomiting
50/0, SAG
at True Acupoints, SAG
during the First Two 1: 50/0,
1: Using Acupressure
Hours (0–2 Hours) SAG 2: 50/
Wrist Band at Non-
and the Following 22 0, SAG 3:
Acupoints, SAG 2:
Hours (2–24 Hours) 50/0
Using Acupressure
after Surgery Wrist Band at Non- Acupoints + Metoclopramide, SAG 3: Using Acupressure Wrist
Band at Non- Acupoints + Ondansetron
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 9 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Bao et al. 2011 [38], The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, United States
Pain Intensity (VAS) 0 Mild and Transient Bruising or A Rash at the Acupressure Site (n = 10)
Majholm & Møller 2011 [39], Copenhagen University Hospital, Denmark
Pain in Cancer
Total: 78/
TAG: Acupressure at Patients
1, TAG:
True Acupoints using undergoing Bone
38/1, SAG:
Magnetic Acupressure Marrow Aspiration
40/0
Suction Cups and Biopsy
+ Standard Local (BMAB)
Analgesics, SAG: Acupressure at Non- Acupoints using Magnetic Acupressure Suction Cups + Standard Local Analgesics
0 Redness (n = 40),
Swelling (n = 17), Tenderness (n = 16), and Paresthesias (n = 4) Sinha et al. 2011 [40], A Single Tertiary Maternity Unit,
Australia
Postoperative
Total: 134/
TAG: Acupressure at
Postoperative Nausea and
22, TAG:
True Acupoints using
Nausea and/or Vomiting
67/8, SAG:
Acupressure Band,
Vomiting 67/14
SAG: Acupressure at Non-Acupoints using Acupressure Band
0 Discomfort from
Band (n = 25)
Wang et al. 2008 [41], A Hospital (Details not Described), United States
Nausea and
Total: 340/
TAG: Acupressure at
Incidence of Nausea Vomiting during
11, TAG:
True Acupoints using
and/or Vomiting Labour and
170/6,
Acupressure Band, Delivery
SAG: 170/
SAG: Acupressure at 5
Non-Acupoints using Placebo Acupressure Band
++ Not Reported2
Turgut et al. 2007 [42], Department of Anesthesiology, Ankara Oncology Hospital, Turkey
Pre-Procedural
Total: 52/
TAG: Acupressure at
Anxiety Level (State Anxiety and Intra-
0, TAG:
True Acupoints using
Anxiety Inventory for Procedural
26/0, SAG:
Acupressure Beads,
Children) Propofol Needs in
26/0
SAG: Acupressure at Children
Non-Acupoints using Undergoing
Acupressure Beads Anesthesia
++ Erythema and
Swelling of the Treated Hand (n = 1)
Heazell et al. 2006 [43], A Single Secondary Care Center, United Kingdom
Postoperative
Total: 102/
TAG: Acupressure at
Severity of Nausea and
2, TAG:
True Acupoints using
Postoperative Vomiting
51/1, SAG:
Acupressure Band,
Nausea and Vomiting 51/1
SAG: Acupressure at Non-Acupoints using Acupressure Band
No Discomforts Found in the Study
Wang et al. 2005 [44], A Hospital (Details not Described), United States
Nausea and
Total: 80/
TAG: Acupressure at
No. of Days of
0 (For No. of Days Vomiting in Early
0, TAG:
True Acupoints using
Hospital Stay, and
of Hospital Stay), + Pregnancy
40/0, SAG:
Acupressure Band,
No. of Patients Who
+ (For No. of 40/0
SAG: Acupressure at
Required ≧ 4 Days in
Patients Who Non-Acupoints using
the Hospital
Required ≧ 4 Days Acupressure Band
in the Hospital) Preoperative
Total: 61/
TAG: Acupressure at
Parental Anxiety
++ Not Reported2 Parental Anxiety
NR, TAG:
True Acupoints using
(State Anxiety 28/NR,
Acupressure Beads,
Inventory) SAG: 33/
SAG: Acupressure at NR
Non-Acupoints using Acupressure Beads
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 10 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Alkaissi et al. 2005 [45], Department of Otolaryngology, University Hospital of Linköping, Sweden
Feeling Uncomfortable and Tight (n = 2), and Swelling of the Hand (n = 1)
Samad et al. 2003 [46], Aga Khan University Hospital, Pakistan
Tolerance to
Total: 60/
TAG: Acupressure at
Time to the Onset of
+, Mean Time to Nauseogenic
0, TAG:
True Acupoints using
Moderate Nausea
Moderate Nausea Motion Stimulation
20/0, SAG:
Acupressure Band,
was Statistically 20/0, CG:
SAG: Acupressure at
Longer in TAG than 20/0
Non-Acupoints using
That in CG, SCG Acupressure Band, CG:
was also Longer No Acupressure
than CG but There was no Statistical Significance 0 Not Reported2
Alkaissi et al. 2002 [47], University Hospital of Linköping, Sweden
Postoperative
Total: 50/
TAG: Acupressure at
Incidence of Nausea Nausea and
0, TAG:
True Acupoints using
and Vomiting Vomiting
25/0, SAG:
Wrist-Band with Plastic 25/0
Bead, SAG: Acupressure at Non- Acupoints using Wrist- Band with Plastic Bead
Discomforts, Red Indentation or Itching (n = 15), Headache and Dizziness (n = 1), Deep Marks, Blistering or Swelling (n = 45)
Agarwal et al. 2000 [48], Setting not Described, India
Postoperative
Total: 410/
TAG: Acupressure at
Complete Response
+,Both TAG and Nausea and
30, TAG:
True Acupoints using
of Postoperative
SAG were Better Vomiting
135/NR,
Acupressure Band
Nausea and Vomiting
than CG SAG: 139/
+ Routine Anesthesia,
(No Report of NR, CG:
SAG: Acupressure at
Nausea, Vomiting or 136/NR
Non-Acupoints using
Rescue Medication) Acupressure Band + Routine Anesthesia, CG: Routine Anesthesia
+ No AEs Found in
the Study
Harmon et al. 2000 [49], Rotunda Hospital, Ireland
Postoperative
Total: 200/
TAG: Acupressure at
Postoperative Nausea and
0, TAG:
True Acupoints using
Nausea and Vomiting Vomiting
100/0,
Acupressure Bands, SAG: 100/
SAG: Acupressure at 0
Non-Acupoints using Acupressure Bands
++ Not Reported2
Harmon et al. 1999 [50], Rotunda Hospital, Ireland
Nausea and
Total: 94/
TAG: Acupressure at
Nausea and Vomiting Vomiting during
NR, TAG:
True Acupoints using
during and after and after Surgery
47/NR,
Acupressure Band,
Surgery SAG: 47/
SAG: Acupressure at NR
Non-Acupoints using Acupressure Band
++ No AEs Found in
the Study
Alkaissi et al. 1999 [51], University Hospital of Linköping, Sweden
Postoperative
Total: 104/
TAG: Acupressure at
Postoperative Nausea and
0, TAG:
True Acupoints using
Nausea and Vomiting Vomiting
52/0, SAG:
Acupressure Band, 52/0
SAG: Acupressure at Non-Acupoints using Acupressure Band Postoperative
Total: 60/
TAG: Acupressure at
Complete Response
0, Both TAG and
Not Reported2
Nausea and
10, TAG:
True Acupoints using
of Postoperative
SAG were Better Vomiting
20/NR,
Acupressure Band
Nausea and Vomiting
than CG, but There SAG: 20/
+ Routine Anesthesia,
(No Report of
were No Statistical NR, CG:
SAG: Acupressure at
Nausea, Vomiting or
Significances 20/NR
Non-Acupoints using
Rescue Medication) Acupressure Band + Routine Anesthesia, CG: Routine Anesthesia
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 11 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Fan et al. 1997 [52], Maimonides Medical Center, United States
++ No AEs Found in
the Study
O’Brien et al. 1996 [53], Setting Not Described, Canada
Postoperative
Total: 200/
TAG: Acupressure at
Postoperative Nausea and
0, TAG:
True Acupoints using
Nausea and Vomiting Vomiting
108/0,
Acupressure Band, SAG: 92/0
SAG: Acupressure at Non-Acupoints using Acupressure Band
Not Reported2
Felhendler & Lisander 1996 [54], An Ambulatory Unit in Linköping University Hospital, Sweden
Nausea and
Total: 161/
TAG: Acupressure at
Nausea and Vomiting
0, No Difference Vomiting During
12, TAG:
True Acupoints using
(The Rhodes Index of
was Detected Pregnancy
54/NR,
Acupressure Band,
Nausea, Vomiting,
Across Groups SAG: 53/
SAG: Acupressure at
and Retching) NR, CG:
Non-Acupoints using 54/NR
Acupressure Band, CG: No Acupressure
++ Not Reported2
Bayreuther et al. 1994 [55], Five General Practices in Central Southampton, United Kingdom
Postoperative Pain Total: 40/
TAG: Acupressure at
Postoperative Pain NR, TAG:
True Acupoints using A
(VAS) 20/NR,
Dentist’s Tool, SAG: SAG: 20/
Acupressure at Non- NR
Acupoints using A Dentist’s Tool
Nausea (VAS) ++ Not Reported2
Type 3—Pseudo-Intervention at the Same Acupoints as Intervention Group: Manual Light-Touch without Acupressure
Hamidzadeh et al. 2012 [56], Fatemiyeh Educational and Research Hospital in Shahroud, Iran
Early Morning
Total: 23/
TAG: Acupressure at Sickness
8, TAG:
True Acupoints using 11/4, SAG:
Acupressure Band, 12/4
SAG: Acupressure at Non-Acupoints using Acupressure Band
++ No AEs Found in
the Study
Mirbagher-Ajorpaz et al. 2011 [57], Dormitories of Kashan University of Medical Science, Iran
Labor Pain Total: 100/
TAG: Manual
Intensity of Labor 0, TAG:
Acupressure at True
Pain (VAS) 50/0, SAG:
Acupoints, SAG: Light 50/0
Touch on the Same Acupoints
++ Not Reported2
Sun et al. 2010 [58], Two Long-Term Care Facilities in Northern Taiwan, Taiwan
Primary
Total: 30/
TAG: Manual
Severity of Dysmenorrhea
0, TAG:
Acupressure at True
Dysmenorrhea (VAS) 15/0, SAG:
Acupoints, SAG: Light 15/0
Touch on the Same Acupoints
++ Not Reported2
Kashanian & Shahali 2010 [59], Akbarabadi Teaching Hospital in Tehran, Iran
Insomnia Total: 50/
TAG: Manual
Insomnia (The Athens 6, TAG:
Acupressure at True
Insomnia Scale- 25/2, SAG:
Acupoints, SAG: Light
Taiwan Form) 25/4
Touch on the Same Acupoints
++ Not Reported2
Hjelmstedt et al. 2010 [60], Sree Avittom Thirunal Hospital in Trivandrum, India
Duration and Pain
Total: 120/
TAG: Manual
Severity of Labor of the Active
0, TAG:
Acupressure at True
Pain (VAS) and Phase of Labor
60/0, SAG:
Acupoints, SAG: Light
Duration of Active 60/0
Touch on the Same
Phase Acupoints Labor Pain Total: 213/
TAG: Manual
Intensity of Labor
++, TAG was
Not Reported2 1, TAG:
Acupressure at True
Pain (VAS)
Significantly Better 71/0, SAG:
Acupoints + Usual
than CG; SAG was 71/0,
Care, SAG: Light Touch
Better than CG but CG:71/1
on the Same Acupoints
There was no + Usual Care, CG:
Statistical Usual Care
Significance
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 12 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Hsu et al. 2006 [61], Two Long-Term Care Facilities, Taiwan
++ Not Reported2
Lee et al. 2004 [62], Delivery Room in A University Hospital, South Korea
Insomnia Total: 50/
TAG: Manual
Insomnia (Pittsburgh 0, TAG:
Acupressure at True
Sleep Quality Index) 25/0, SAG:
Acupoints, SAG: Light 25/0
Touch on the Same Acupoints
++ Not Reported2
Type 4—Pseudo-Intervention at the Same Acupoints as Intervention Group: Placebo Acupressure Devices Nilsson et al.
2015 [63], Department of Neurosurgery of Umeå University Hospital, Sweden
Labor Pain and
Total: 89/
TAG: Manual
Severity of Labor Length of Delivery
14, TAG:
Acupressure at True
Pain (VAS) and Time
36, SAG:
Acupoints, SAG: Light
Duration of Labor to 39
Touch on the Same
Delivery Acupoints
0 Swelling (n = 12),
Bruises (n = 2), Paresthesia (n = 1), and Pain (n = 1)
Molassiotis et al. 2013 [64], Christie NHS Foundation Trust, Clatterbridge Centre for Oncology, Southport General Infirmary,
and Several Hospitals, United Kingdom
Postoperative
Total: 120/
TAG: Acupressure at
Postoperative Nausea and
25, TAG:
True Acupoints using
Nausea (NRS) Vomiting
52/9, SAG:
Acupressure Band, 68/16
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
Transient AEs (n = 6): Minor Swelling and Tightness in the Area of Wristbands, and Discomfort when Wearing the Wristbands
Noroozinia et al. 2013 [65], Imam Khomeini General Hospital of Urmia, Iran
Chemotherapy-
Total: 500/
TAG: Acupressure at
Chemotherapy-
0, Nausea Induced Acute and
128, TAG:
True Acupoints using
Induced Nausea (The
Experience was Delayed Nausea
168/36,
Acupressure Band
Nausea Experience
slightly lower in SAG: 166/
+ Standard Antiemetics,
Subscale of The
Both TAG and SAG 47, CG:
SAG: Sham
Rhodes Index of
than that in CG, but 166/45
Acupressure at the
Nausea, Vomiting,
There was No Same Acupoints using
and Retching)
Statistical A Placebo Acupressure
Significance Band+ Standard Antiemetics, CG: Standard Antiemetics
++ Not Reported2
Soltanzadeh et al. 2012 [66], Hospital (Details not Described), Iran
Postoperative
Total: 152/
TAG: Acupressure at
Postoperative Nausea and
0, TAG:
True Acupoints using
Nausea and Vomiting Vomiting
76/0, SAG:
Acupressure Band,
(VAS) 76/0
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band Postoperative
Total: 120/
TAG: Acupressure at
Incidence of
++ (For Nausea), +
No AEs Found in
Nausea and
0, TAG:
True Acupoints using
Postoperative
(For Vomiting)
the Study Vomiting
40/0, SAG
Acupressure Band,
Nausea and Vomiting 1: 40/0,
SAG 1: Sham SAG 2: 40/
Acupressure at the 0
Same Acupoints using A Dummy Band, SAG 2: Sham Acupressure at the Same Acupoints using A Dummy Band +
Metoclopramide
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 13 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
White et al. 2012 [67], Cedars Sinai Medical Center in Los Angeles, United States
++ Constipation
(n = 2), Headache (n = 3), Fatigue (n = 6), and Drowsiness (n = 3)5
Ho et al. 2006 [68], Taipei Veterans General Hospital, Taiwan
Postoperative
Total: 100/
TAG: Acupressure at
Incidence of Nausea and
0, TAG:
True Acupoints using
Postoperative Vomiting
50/0, SAG:
Acupressure Strip,
Nausea and Vomiting 50/0
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Strip
+ No AEs Found in
the Study
Klein et al. 2004 [69], Toronto General Hospital, Canada
Nausea and
Total: 110/
TAG: Acupressure at
Incidence of Nausea Vomiting During
0, TAG:
True Acupoints using
and Vomiting During Surgery
55/0, SAG:
Acupressure Band,
Surgery 55/0
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
+ No AEs Found in
the Study
Schultz et al. 2003 [70], A Tertiary Care Hospital in Northern New England, Portland
Postoperative
Total: 152/
TAG: Acupressure at
Incidence of Nausea and
0, TAG:
True Acupoints using
Postoperative Vomiting
75/0, SAG:
Acupressure Band,
Nausea and Vomiting 77/0
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
Not Reported2
Dent et al. 2003 [71], The Coronary Care Unit of A District Hospital, United Kingdom
Postoperative
Total: 143/
TAG 1: Acupressure
Incidence of
—(For Nausea),— Nausea and
40, TAG
Band at True Acupoints
Postoperative
(For Vomiting) 6 Vomiting
1:30, TAG
+ Droperidol, TAG 2:
Nausea and Vomiting 2:24, SAG
Acupressure Band at 1:24, SAG
True Acupoints 2:25
+ Placebo Drug, SAG 1: Placebo Band at the Same Acupoints + Droperidol, SAG 2: Placebo Band at the Same Acupoints +
Placebo Drug
Not Reported2
Norheim et al. 2001 [72], A University Hospital, Norway
Acute Myocardial
Total: 301/
TAG: Acupressure at
Incidence of Nausea
+,TAG was Better Infarction-Related
0, TAG:
True Acupoints using
and Vomiting
than SAG and CG, Nausea and
95/0, SAG:
Acupressure Band,
No Difference was Vomiting
98/0, CG:
SAG: Sham
Found between 108/0
Acupressure at the
SAG and CG Same Acupoints using A Placebo Acupressure Band, CG: No
Additional Intervention Morning Sickness
Total: 97/
TAG: Acupressure at
Incidence and
+ (For Incidence of
Pain, Numbness, in
Pregnancy
13, TAG:
True Acupoints using
Duration of Nausea
Nausea and
Soreness, and NR, SAG:
Acupressure Band,
and Vomiting
Vomiting), ++ (For
Swelling (No. not NR
SAG: Sham
Duration of Nausea
Given); Worse Acupressure at the
and Vomiting)
Symptoms (n = 3) Same Acupoints using A Placebo
Acupressure Band
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 14 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Steele et al. 2001 [73], Seventeen Medical Clinics or Offices in Southern Michigan, United States
++ Not Reported2
Woods 1999 [74], Malcolm Grow Air Force Medical Center, United States
Nausea and
Total: 138/
TAG: Acupressure at
Severity and Vomiting During
28, TAG:
True Acupoints using
Frequency of Nausea Pregnancy
85/17,
Acupressure Band,
and Vomiting SAG: 53/
SAG: Sham 11
Acupressure at the Same Acupoints using A Placebo Acupressure Band
- Not Reported2
Duggal et al. 1998 [75], Hospital (Details not Described), Canada
Postoperative
Total: 10/
TAG: Acupressure at
Postoperative Nausea and
NR, TAG:
True Acupoints using
Nausea and Vomiting Vomiting
5/NR,
Acupressure Band,
(VAS) SAG: 5/NR
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
+ Tightness (n = 22),
Swollen Hands (n = 43), Infusion Problem (n = 4), and Itching Wrists (n = 9)
Lewis et al. 1991 [76], Hospital (Details not Described), United States
Postoperative
Total: 263/
TAG: Acupressure at
Incidence of Nausea Nausea and
19, TAG:
True Acupoints using
and Vomiting Vomiting
122, SAG:
Acupressure Band, 122
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
0 Bands were Well
Tolerated
Type 5—Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Manual Acupressure Suh 2012 [77], A
University Cancer Center in Seoul, South Korea
Postoperative
Total: 66/
TAG: Acupressure at
Incidence of Nausea and
2, TAG:
True Acupoints using
Postoperative Vomiting
33/2, SAG:
Acupressure Band,
Nausea and Vomiting 33/0
SAG: Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band
Not Reported2
Lang et al. 2007 [78], A Paramedic- Based Rescue System, Austria
Chemotherapy-
Total: 120/
TAG 1: Acupressure at
Chemotherapy-
++ (For Acute and Induced Nausea
15, TAG
Therapeutic Acupoints
Induced Nausea and
Delayed Vomiting) 7 and Vomiting
1:30/5,
using Acupressure
Vomiting (The Index TAG 2:30/
Band, TAG 2:
of Nausea, Vomiting, 1, SAG:
Acupressure at
and Retching) 30/7,
Therapeutic Acupoints CG:30/2
using Acupressure Band + Counseling, SAG: Manual Acupressure at Irrelevant Acupoints, CG: Counseling Only Pre-Hospital
Total: 32/
TAG: Manual
Intensity of Pain and
++ (For Pain,
Not Reported2
Analgesia
1, TAG:
Acupressure at
Anxiety (VAS), and
Anxiety and Heart 16/1, SAG:
Therapeutic Acupoints,
Blood Pressure and
Rate), 0 (Blood 16/0
SAG: Manual
Heart Rate
Pressure) Acupressure at Irrelevant Acupoints
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 15 / 40
Table 2. (Continued)
Study & Setting(s) Condition(s) Sample
Size & Dropout (N/n)
Acupressure- related AEs
Wu et al. 2007 [79], Wu et al. 2004 [80], A Medical Center and Three Regional Hospitals in Taipei, Taiwan
++ Not Reported2
Type 6—Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Acupressure Bands or Other Devices Nordio
& Romanelli 2008 [81], Setting not Described, Italy
Chronic Dyspnea
Total: 62/
TAG: Manual
Depression (The in Chronic
18, TAG:
Acupressure at
Geriatric Depression Obstructive
22, SAG:
Therapeutic Acupoints,
Scale), Anxiety (The Pulmonary
22
SAG: Manual
State Anxiety Disease
Acupressure at
Inventory), Chronic Irrelevant Acupoints
Dyspnea (Pulmonary Function Status and Dyspnea Questionnaire Modified and VAS), and Six-Minute Walking Tests
Insomnia Total: 40/
TAG: Acupressure at
Level of Global Life
NR (For Life
No AEs Found in 7, TAG:
Therapeutic Acupoints
Quality (General
Quality,
the Study 20/2, SAG:
using Wrist
Health
Comparison 20/5
Acupressure Device,
Questionnaire), Sleep
between Groups SAG: Acupressure at
Quality (Pittsburgh
was not Shown), ++ Irrelevant Acupoints
Sleep Quality Index),
(For Sleep Quality), using Wrist
and Anxiety (State
+ (For Anxiety), ++ Acupressure Device
Trait Anxiety
(For Urinary Inventory); and
Melatonin Urinary Melatonin
Metabolite) Metabolite
AE: Adverse event, TAG: True acupressure group, SAG: Sham acupressure group, VAS: Visual Analogue Scale, NA: Not
applicable, CG: Control group, SGRQ: The Saint George Respiratory Questionnaire, NRS: Numerical Rating Scale 1: For true
acupressure group 1 and sham acupressure group 2: The study did not assess acupressure-related adverse events 3: Statistical
analysis was not conducted for vomiting 4: For true acupressure group and sham acupressure group 1 5: Incidence of
postoperative adverse events, not sure whether these events were associated with acupressure 6: For true acupressure group 1 and
sham acupressure group 1 7: For true acupressure group 1 and sham acupressure group. 4Vote counts of results of therapeutic
effects: “++”: True acupressure group is significantly better than sham acupressure group for the main outcome; “+”: Trend of
the main outcome in favor of true acupressure group but without statistical significance; “0”: No difference was found between
true and sham acupressure groups; “−”:Trend of the main outcome in favor of sham acupressure group but without statistical
significance; “− −”: sham acupressure group is significantly better than true acupressure group for the main outcome.
doi:10.1371/journal.pone.0132989.t002
Sham Acupressure Controls Used in Randomized Controlled Trials
Intervention & Control
Main Outcome(s) Therapeutic Groups
Effects of Acupressure*
Methodological Quality and Risk of Bias of the Included Studies
Results of the risk of bias assessment for all the included trials can be seen in S3 Table. Method- ological quality of
the included trials was generally satisfactory, as already all studies of high risk of bias were excluded. Forty-nine
trials adequately described the method of randomization. Twenty-six studies appropriately described the allocation
concealment. Blinding of partici- pants was adopted in 45 trials. Outcome assessor was blinded to the intervention in
the major- ity of studies (51 studies), but there were only 17 studies which reported blinding for the care provider.
Eighteen studies employed a single-blind design for either participant, or care pro- vider, or outcome assessor.
Double-blinding for both participant and outcome assessor was uti- lized in 26 trials, and blinding for both the care
provider and the outcome assessor was used in
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 16 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
four studies. There were 11 trials that incorporated a triple-blind design. No trial tested the credibility of blinding
during the study period.
Dropout of study subjects was mentioned and acceptable in 89.4% of the included studies. Thirty-two trials
reported that all randomized participants were included for analysis. Selective outcome reporting was detected in
only one study, and baseline data were similar between groups in most of the studies. Co-intervention (e.g.
intra-operative anesthesia or standard care, etc.) was similar or avoidable in more than half of the articles (42
studies). Participants’ compli- ance to treatment was mentioned and satisfactorily achieved in seven studies. The
timing of outcome assessment was found similar among groups in 96.97% of the included trials.
Description of Acupressure Protocols
True acupressure protocols used in the included trials are presented in Table 3. Among the analyzed trials, 30
adopted manual acupressure while another 36 chose acupressure equipment to provide constant pressure on the
targeted acupoints. The majority (52 studies) described the person conducting acupressure, being an acupuncturist,
acupressure practitioner, anesthetist, nurse, paramedic and study investigator, etc. For studies where acupressure was
administered by non-acupuncture/acupressure professionals, 60% (27/45) specified that the intervention operator
had received training in acupressure or application of the acupressure device. Length of acupressure therapy varied
significantly among studies due to the nature of the treated con- ditions. The shortest intervention (three minutes)
emerged in one study focusing on pre-hospi- tal analgesia [33] while the longest treatment was five months for
cancer-related fatigue [16]. Fifty studies reported the intensity for acupressure, 24 claimed equal intensity between
groups, while sham groups received only light acupressure or no stimulation in the other 26 studies.
For the types of acupressure, 61 articles employed Chinese acupuncture theory to guide the acupressure protocol,
and three adopted the Japanese Jin Shin acupressure [20, 24, 27], while the other two used Korean hand acupressure
[30,66]. Bilateral acupoints were stimulated in both groups in 38 studies, and eight trials only employed unilateral
stimulation, while in the other 20 studies, both bilateral and unilateral acupoints were used or such information were
not reported. The number of selected acupoints ranged from one to 15 in the true treatment groups, and the majority
(50 studies) only applied one acupoint (bilateral or unilateral) for acu- pressure. In one study on postoperative pain
[54], 15 acupoints were chosen for stimulation. Selection of the acupoints was based on the targeted health issue,
and neiguan (P6) was fre- quently used for controlling nausea and/or vomiting, sanyinjiao (SP6) and hegu (LI4)
were used for treating various types of pain such as peri-operative pain, primary dysmenorrheal and labor pain,
shenmen (HT7) was mainly used for sleep disorders, and yintang (EX-NH3) was used for anxiety relief.
Description of Sham Acupressure Procedures
Sham acupressure protocols are also summarized in Table 3. Six types of sham acupressure were identified.
Non-acupoint was used in 40 studies, of which, 19 manually stimulated the non-acupoint (type 1). For studies with
type 1 sham mode, 12 described the definite location of the selected non-acupoints and most of them were near the
real acupoints used in the true intervention groups. More specifically, three studies [25, 26, 32] indicated that the
non-acu- points should be away from the nearby meridians, with 0.5 cun (a traditional Chinese term that translates to
"anatomical inch") in one study [26], and one cm in another [32]. In addition, there was one study [31] stating that
the non-acupoints should be three to four cm away from the targeted active acupoints. Total duration of treatment as
well as duration of each session were similar between groups. In terms of the acupressure intensity, three studies
[19, 22, 25]
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 17 / 40
applied equal pressure between groups, and one [23] only exerted light pressure on non-acu- points, while this
information was not reported in the other 15 articles.
Twenty-one studies used acupressure devices at the non-acupoints (type 2). Both true and sham study arms
utilized the same equipment. Wrist bands such as sea-bands or vital-bands, etc. were adopted in 16 studies and these
tools usually possess a plastic/metal button located at
Table 3. True and Sham Acupressure Protocols of the Included Studies.
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Type 1—Sham Acupressure at Non-Acupoints: Manual Acupressure (19 Studies) Tang et al. 2014 [16]
Nurse Students with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Hegu (LI4), Zusanli (ST36), and Sanyinjiao
(SP6)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints at Inner Ankle, Patella, and
the First Metacarpal Head
Total Duration: Daily Treatment for Consecutive 5 Months, Each Treatment: 6 Min with 1 Min for Each Acupoint
Not Reported
Atrian et al. 2013 [17]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Taichong (LR3)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints located 2 cm above the
Distance between the Third and Fourth Toes
Total Duration: NR (3 Treatments in Total), Each Treatment: 16 Mins (Each Acupoint on Each Leg for 2 Min Pressure and 2
Min Resting, Repeated Twice)
Not Reported
Sehhatie- Shafaie et al. 2013 [18]
Research Assistant with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6), and Hegu (LI4)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints on the Legs and Hands
(Details not Described)
Total Duration: Four Treatments in Total, Each Treatment: 20 Min
Not Reported
Chao et al. 2013 [19]
Research Nurse with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Zusanli (ST36)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Tibia
Total Duration: 3 Treatments Per Day for 5 Days, Each Treatment: 5 Continuous 1-second Press followed by a 2-Second Rest,
Repeated for 3 Min
Equal for Both TA and SA
McFadden et al. 2012 [20]
Acupressure Practitioner
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints which cannot be Found on Established
Acupressure Point Charts (Details not Described)
Total Duration: 40 Min (Only One Treatment)
Not Reported
Valiee et al. 2012 [21]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3), and Shenmen (Ear)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints located at the External Corner of the
Left Eyebrow, and the Entrance of the Cavity of the Ear
Total Duration: 10 Min (Only One Treatment)
Not Reported
Rad et al. 2012 [22]
Researcher with the Certificate of Conducting Acupressure
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Youmen (KI21)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Unilateral) No-Acupoint (Details Not Described)
Total Duration: Daily Treatment for 4 Consecutive Days, Each Treatment: 2 Min Acupressure followed by 2 more Min Massage
at the Acupoints, Repeated for 20 Min
Equal for Both TA and SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 18 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Chang et al. 2011 [23]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Zhongji (CV3), Guanyuan (CV4), Qihai (CV6),
Shenshu (BL23), Pangguangshu (BL28), Ciliao (BL32), Sanyinjiao (SP6), and Zusanli (ST36)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints (Details Not Described)
Total Duration: 3 Treatments Per Week for 10 Weeks, Each Treatment: 30 Min
Unequal (Less in SA, Only Light Pressure)
McFadden et al. 2011 [24]
Acupressure Practitioner
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints which cannot be Found on Established
Acupressure Point Charts (Details not Described)
Total Duration: 2 Treatments Per week for 4 Weeks, Each Treatment: 40 Min
Not Reported
Kashefi et al. 2011 [25]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the Dorsal Side of
the Leg, Away from Meridians and is not Stimulated upon the Achilles Tendon
Total Duration: NR (One Treatment for Each Menstrual Cycle, 2 Treatments in Total), Each Treatment: 6-Second Pressure
followed by 2-Second Rest, Repeated for 30 Min
Equal for Both TA and SA
Reza et al. 2010 [26]
Investigator with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Neiguan (P6), Shenmen (Hand, HT7),
Shenmen (Ear), Yungchuan (KI1), Sanyinjiao (SP6), and Anmian (EX-HN22)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints Located 0.5 cun Away from Meridian
Total Duration: 3 Treatments Per Week for 4 Weeks
Not Reported
McFadden & Hernández 2010 [27]
Acupressure Practitioner
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): True Acupoints (Details not Described)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints which cannot be Found on Established
Acupressure Point Charts (Details not Described)
Total Duration: One Treatment Per Week for 8 Weeks, Each Treatment: 40 Min
Not Reported
Maa et al. 2007 [28]
Investigator Skilled in Acupressure
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Zhongfu(LU1), Chize (LU5), Yuji (LU10),
Fenglong (ST40), and Zusanli (ST36)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints located near Real Acupoints
(where no Acupoints are Known to Exist)
Total Duration: Daily Treatment (at Least) for 8 Weeks, Each Treatment: 30 Seconds to 2 Min Acupressure for Each Acupoint
(Total Duration for Each Treatment not Mentioned)
Not Reported
Shin et al. 2007 [29]
Nurse with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoint located at a Bony Part around the
Radial Pulse at the Wrist
Total Duration: 3 Treatments Per Day, From the Second Day of Hospitalization to the Day before Discharge, Each Treatment: 10
Min (7 Seconds Acupressure Followed by 2 Seconds Rest, Repeated for 10 Min)
Not Reported
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 19 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Bertalanffy et al. 2004 [30]
Paramedic Method(s): Manual
Acupressure at True Acupoints using A Hard Plastic Ball, Selected Acupoint(s): (Bilateral) Korean Hand Acupressure Point
located at the Middle Phalanx of the Fourth Finger (K-K9)
Method(s): Manual Acupressure at Non-Acupoints using A Hard Plastic Ball, Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Middle Phalanx of the Second Finger
Total Duration: From the Time of Randomization to Arrival at the Hospital
Not Reported
Chen et al. 2003 [31]
Research Assistant with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6), Zusanli (ST36), and Sanyinjiao (SP6)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints located at the Tibia or Radial Bone
Surface Approximately 3–4 cm from the Selected True Acupoints
Total Duration: 4 Days in Hospital and Self- Acupressure at Home in the Following Days (Details Not Described), Each
Treatment: 9 Min (3 Min for Each Acupoint)
Not Reported
Tsay & Chen 2003 [32]
Investigator and Research Assistant with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (Hand, HT7), Shenmen (Ear),
Yungchuan (KI1)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoints located 1 cm away from
Meridian
Total Duration: 3 Treatments Per Week for 4 Weeks, Each Treatment: 14 Min
Not Reported
Kober et al. 2002 [33]
Paramedic with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Zhongchong (PC9), Neiguan (P6), Kunlun (BL60),
Hegu (LI4), and Baihui (GV20)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoints located at the Middle of Dorsal Wrist,
Middle of Clavicle, Middle of Patella, Lateral Metacarpophalangeal Junction of the Second Finger, and Middle of Lateral
Malleolus
Total Duration: 3 Min Not Reported
Belluomini et al. 1994 [34]
Not Reported Method(s): Manual
Acupressure at True Acupoints, Selected Acupoint(s): Neiguan (P6)
Method(s): Manual Acupressure at Non-Acupoints, Selected Acupoint(s): Non- Acupoint located at the Palmar Surface of the
Hand, Proximal to the Head of the Fifth Metacarpal Joint
Total Duration: 4 Times Per Day for Consecutive 7 Days, Each Treatment: 10 Min
Not Reported
Type 2—Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices (21 Studies) Adib- Hajbaghery &
Etri, 2013 [35]
Researcher with Acupressure Training
Method(s): Acupressure at True Acupoints using Acupressure Band (PsiBand), Selected Acupoint(s): (Unilateral) Lanwei
(EX-LE7)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (PsiBand), Selected Acupoint(s): (Unilateral) Non-Acupoint
located at the Opposite Site of the Lanwei (EX-LE7) Point
Total Duration: 7 Hours (Loosened for 10 Min every 2 Hours and then Tightened)
Unequal (Less in SA)
Alessandrini et al. 2012 [36]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Part of the Carpus
Total Duration: 30 Min Equal for Both TA
and SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 20 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Soltani et al. 2011 [37]
Not Reported Method(s): Using
Acupressure Wrist Band at True Acupoints, Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Using Acupressure Wrist Band at Non-Acupoints, Selected Acupoint(s): (Bilateral) Non-Acupoint located at the
Posterior Surface of Both Forearms
Total Duration: Applied 30 Min before Induction of Anesthesia and Removed 6 Hours Later
Equal for Both TA and SA
Bao et al. 2011 [38]
Acupressure Operator
Method(s): Acupressure at True Acupoints using Magnetic Acupressure Suction Cups + Standard Local Analgesics, Selected
Acupoint(s): (Bilateral) Hegu (LI4)
Method(s): Acupressure at Non-Acupoints using Magnetic Acupressure Suction Cups, Selected Acupoint(s): (Bilateral)
Non-Acupoint located at the Proximal Dorsum of the Fourth Interosseus Space of the Hand
Total Duration: The Entire BMAB Procedure
Equal for Both TA and SA
Majholm & Møller 2011 [39]
Nursing Assistant Method(s): Acupressure
at True Acupoints using Acupressure Band (Vital- Band), Selected Acupoint(s): (Unilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Vital-Band), Selected Acupoint(s): (Unilateral)
Non-Acupoint located at the Dorsum of the Forearm
Total Duration: Applied just before Induction of Anesthesia and Kept for 24 Hours after Surgery
Equal for Both TA and SA
Sinha et al. 2011 [40]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Pressure RightTM), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Placebo Acupressure Band, Selected Acupoint(s): (Bilateral) Non- Acupoint
located at A Distance of 3 of the Parturient’s Finger- Breadths from the Proximal Palmar Crease
Total Duration: From the Time of Randomization to 2 Hours after Vaginal Delivery or the Time of A Decision of Caesarean
Delivery
Unequal (No Pressure was Applied for SA)
Wang et al. 2008 [41]
Acupuncturist Method(s): Acupressure
at True Acupoints using Acupressure Beads, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3)
Method(s): Acupressure at Non-Acupoints using Acupressure Beads, Selected Acupoint(s): Non-Acupoint (Above the Lateral
Boarder of the Left Eyebrow)
Total Duration: Entire Anesthesia Period (Applied before Enter the Operation Room and Removed at the Completion of the
Procedure)
Equal for Both TA and SA
Turgut et al. 2007 [42]
Anesthesiologist Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Surface of the Forearm
Total Duration: Applied 30 Min before Anesthesia and Kept for 24 Hours after Surgery
Equal for Both TA and SA
Heazell et al. 2006 [43]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Aspect of the Forearm
Total Duration: Not Reported (8 Hours Per Day)
Equal for Both TA and SA
Wang et al. 2005 [44]
Acupuncturist Method(s): Acupressure
at True Acupoints using Acupressure Beads, Selected Acupoint(s): Yintang (or Extra-1, EX-NH3)
Method(s): Acupressure at Non-Acupoints using Acupressure Beads, Selected Acupoint(s): Non-Acupoint (Above the Lateral
Boarder of the Left Eyebrow)
Total Duration: More than 20 Min
Equal for Both TA and SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 21 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Alkaissi et al. 2005 [45]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Side of both Forearms, 4 Fingers Breadth Proximal to the Proximal Flexor Palmar Crease
Total Duration: Not Reported
Equal for Both TA and SA
Samad et al. 2003 [46]
Investigator Method(s): Acupressure
at True Acupoints using Wrist-Band with Plastic Bead, Selected Acupoint (s): (Unilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Wrist- Band with Plastic Bead, Selected Acupoint(s): (Unilateral)
Non-Acupoint located at the Dorsum of the Right Forearm away from P6 Acupoint
Total Duration: Applied 30 Min before Induction of Anesthesia, and Kept for 6 Hours after Surgery
Equal for Both TA and SA
Alkaissi et al. 2002 [47]
Nurse Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Site of the Forearm, 4 Fingers Breadth Proximal to the Flexor Palmar Crease
Total Duration: 24 Hours Equal for Both TA
and SA
Agarwal et al. 2000 [48]
Individual who was Trained in the Application of Acupressure Band
Method(s): Acupressure at True Acupoints using Acupressure Bands, Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Bands, Selected Acupoint(s): (Bilateral) Non- Acupoint located at
the Posterior Surface of the Wrist
Total Duration: Applied 30 Min before Induction of Anesthesia, and Removed 6 Hours after Surgery
Equal for Both TA and SA
Harmon et al. 2000 [49]
Anesthetist Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Unilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Unilateral)
Non-Acupoint located at the Dorsal Site of the Right Forearm
Total Duration: Applied 5 Min before Induction of Anesthesia, and Removed 6 Hours after Discharge to the Ward
Equal for Both TA and SA
Harmon et al. 1999 [50]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Unilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Unilateral)
Non-Acupoint (Details Not Described)
Total Duration: Applied immediately before Induction of Anesthesia, and Removed 20 Min after Induction of Anesthesia
Equal for Both TA and SA
Alkaissi et al. 1999 [51]
Researcher Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsal Site of Both Forearms, 4 Fingers Breadth Proximal to the Proximal Flexor Palmar Crease
Total Duration: Applied just before Surgery, and Removed after Discharge to Home (Details not Described)
Equal for Both Groups
Fan et al. 1997 [52]
Individual who was Trained in the Application of Acupressure Band
Method(s): Acupressure at True Acupoints using Acupressure Band (AcuBand), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (AcuBand), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Dorsum of Both Wrists
Total Duration: Applied before Induction of Anesthesia, and Removed 6 Hours after Surgery
Unequal (AcuBands were Tied Loosely in SA)
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 22 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
O’Brien et al. 1996 [53]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral) Non-Acupoint
located at the Radius of Both Forearms
Total Duration: 3 Days (From the Morning of Study Day 3 to The Morning of Study Day 6)
Equal for Both TA and SA
Felhendler & Lisander 1996 [54]
Researcher Method(s): Acupressure
at True Acupoints using A Dentist’s Tool (A 15-cm Handle with A Ball at the End), Selected Acupoint (s): (Unilateral) Chengqi
(ST1), Lidui (ST45), Yinbai (SP1), Dabao (SP21), Gongsun (SP4), Jingming (BL1), Zhiyin (BL67), Yungchuan (KI1), Youmen
(KI27), Dazhong (KI4), Ligou (LR5), Tongziliao (GB1), Zuqiaoyin (GB44), Dadun (LR1), and Qimen (LR14)
Method(s): Acupressure at Non-Acupoints using A Dentist’s Tool (A 15-cm Handle with A Ball at the End), Selected
Acupoint(s): (Unilateral) Non- Acupoints Situated 2 cm from the Nearest True Acupoints
Total Duration: 30 Min after Patients Awoke from Anesthesia
Unequal (Only Light Pressure for SA)
Bayreuther et al. 1994 [55]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): Neiguan (P6)
Method(s): Acupressure at Non-Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): Non- Acupoint located
Above or Below the Elbow
Total Duration: 7 Days Equal for Both TA
and SA
Type 3—Pseudo-Intervention at the Same Acupoints as Intervention Group: Manual Light-Touch without Acupressure
(7 Studies) Hamidzadeh et al. 2012 [56]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Hegu (LI4)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Hegu (LI4)
Total Duration: 20 Min (5 Pressure Per Min)
No Pressure was Applied for SA
Mirbagher- Ajorpaz et al. 2011 [57]
Researcher with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): Sanyinjiao (SP6)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): Sanyinjiao (SP6)
Total Duration: 20 Min (10 Second-Cycle repeated 120 Times)
No Pressure was Applied for SA
Sun et al. 2010 [58]
Research Assistant with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (HT7)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Shenmen (HT7)
Total Duration: Daily Treatment for Consecutive 5 Weeks, Each Treatment: 5-Second Pressure Followed by 1-Second Rest,
Repeated for 5 Min
No Pressure was Applied for SA
Kashanian & Shahali 2010 [59]
Investigator Method(s): Manual
Acupressure at True Acupoints, Selected Acupoint(s): Sanyinjiao (SP6)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): Sanyinjiao (SP6)
Total Duration: 30 Min No Pressure was
Applied for SA
Hjelmstedt et al. 2010 [60]
A Person with Acupressure Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Sanyinjiao (SP6)
Total Duration: 30 Min No Pressure was
Applied for SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 23 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Hsu et al. 2006 [61]
Researcher with TCM Training
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Shenmen (HT7)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Shenmen (HT7)
Total Duration: Daily Treatment (5 Min) for Consecutive 5 Weeks
No Pressure was Applied for SA
Lee et al. 2004 [62]
Research Intervener
Method(s): Manual Acupressure at True Acupoints, Selected Acupoint(s): (Bilateral) Sanyinjiao (SP6)
Method(s): Light Touch (without Acupressure) on the Same Acupoints, Selected Acupoint (s): (Bilateral) Sanyinjiao (SP6)
Total Duration: 30 Min During Each Uterine Contraction
No Pressure was Applied for SA
Type 4—Pseudo-Intervention at the Same Acupoints as Intervention Group: Placebo Acupressure Devices (14 Studies)
Nilsson et al. 2015 [63]
Nurse Anesthetist Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Unilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Unilateral) Neiguan (P6)
Total Duration: 2 Days No Pressure was
Applied for SA
Molassiotis et al. 2013 [64]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band with the Plastic Button located at the
Exterior of the Wrist Band, Selected Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: 7 Days No Pressure was
Applied for SA
Noroozinia et al. 2013 [65]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band, Selected Acupoint(s): Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Pressure Button, Selected
Acupoint(s): Neiguan (P6)
Total Duration: 30 Min Prior to Spinal Anesthesia
No Pressure was Applied for SA
Soltanzadeh et al. 2012 [66]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band, Selected Acupoint(s): (Bilateral) Korean Hand Acupressure Point (K-K9) located at
the Middle Phalanx of the Fourth Finger on Both Hands
Method(s): Sham Acupressure at the Same Acupoints using A Dummy Band (Details not Described), Selected Acupoint (s):
(Bilateral) Korean Hand Acupressure Point (K-K9) located at the Middle Phalanx of the Fourth Finger on Both Hands
Total Duration: Applied 15 Min Prior to Induction of Anesthesia and Kept for 24 Hours
Not Reported
White et al. 2012 [67]
Investigator Method(s): Acupressure
at True Acupoints using Acupressure Strip, Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Strip without the Pressure Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: Applied 30 to 60 Min before Induction of Anesthesia and Kept for 72 Hours after Surgery
No Pressure was Applied for SA
Ho et al. 2006 [68]
Acupuncturist Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band with A Blunted Plastic Button,
Selected Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: Applied More than 30 Min before Induction of Anesthesia and Removed after Arrival in the Post-Anesthesia
Care Unit
No Pressure was Applied for SA
Klein et al. 2004 [69]
Not Reported Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: Applied before Induction of Anesthesia and Removed 24 Hours after Extubation
No Pressure was Applied for SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 24 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Schultz et al. 2003 [70]
Preoperative Nurse Method(s): Acupressure
Band (Sea-Band) at True Acupoints + Droperidol, Selected Acupoint(s): Neiguan (P6)
Method(s): Placebo Band (with A Flat Button) at the Same Acupoints, Selected Acupoint (s): Neiguan (P6)
Total Duration: Not Reported
No Pressure was Applied for SA
Dent et al. 2003 [71]
Nurse who was Trained in Accurate Location of Targeted Acupoints
Method(s): Acupressure at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: 24 Hours No Pressure was
Applied for SA
Norheim et al. 2001 [72]
Study Assistant Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: 4 Days No Pressure was
Applied for SA
Steele et al. 2001 [73]
Nurse who was Trained in the Application of Acupressure Band
Method(s): Acupressure at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: 4 Days No Pressure was
Applied for SA
Woods 1999 [74]
Anesthesia Provider Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: Applied at Least 15 Min before Induction of Anesthesia and Kept for 24 Hours after Surgery
No Pressure was Applied for SA
Duggal et al. 1998 [75]
Nurse Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Plastic Button, Selected
Acupoint(s): (Bilateral) Neiguan (P6)
Total Duration: At Least 10 Hours
No Pressure was Applied for SA
Lewis et al. 1991 [76]
Investigator Method(s): Acupressure
at True Acupoints using Acupressure Band (Sea- Band), Selected Acupoint(s): (Bilateral) Neiguan (P6)
Method(s): Sham Acupressure at the Same Acupoints using A Placebo Acupressure Band without the Stud, Selected Acupoint(s):
(Bilateral) Neiguan (P6)
Total Duration: Applied 1 Hour before Operation and Kept until Discharge from Hospital on the same Day
No Pressure was Applied for SA
Type 5—Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Manual Acupressure (4 Studies) Suh 2012
[77] Researcher and
Research Assistant
Method(s): Acupressure at Therapeutic Acupoints using Acupressure Band (Sea-Band), Selected Acupoint(s): (Bilateral)
Neiguan (P6)
Method(s): Manual Acupressure at Non- Therapeutic (Irrelevant) Acupoints, Selected Acupoint (s): (Bilateral) Houxi (SI3)
Total Duration: 5 Days Unequal
(Continuously Automatic Pressure for TA and Manual Acupressure for SA) Lang et al. 2007 [78]
Paramedic with Acupressure Training
Method(s): Manual Acupressure at Therapeutic Acupoints, Selected Acupoint(s): Baihui (GV20) and Hegu (LI4, Unilateral)
Method(s): Manual Acupressure at Non- Therapeutic (Irrelevant) Acupoints, Selected Acupoint (s): Geshu (BL17) and Jianliao
(TE14, Unilateral)
Total Duration: Not Reported (3 Min Acupressure for Each Acupoint)
Equal for Both TA and SA
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 25 / 40
Table 3. (Continued)
Study Practitioner True Acupressure (TA) Sham Acupressure (SA) Intervention Duration Acupressure
Intensity
Wu et al. 2007 [79]Wu et al. 2004 [80]
Investigator with Acupressure Training
Method(s): Manual Acupressure at Therapeutic Acupoints, Selected Acupoint(s): Dazhui (GV14), Tiantu (CV22), Feishu (B13,
Bilateral), Shenshu (B23, Bilateral), and Yuji (L10, Unilateral)
Method(s): Manual Acupressure at Non- Therapeutic (Irrelevant) Acupoints, Selected Acupoint (s): Shangqiu (SP5), Taibai
(SP3), and Dadun (LR1)
Total Duration: 5 Treatments Per Week for Consecutive 4 Weeks, Each Treatment: 16 Min
Equal for Both TA and SA
Type 6—Acupressure at Non-Therapeutic Acupoints (Irrelevant Acupoints): Acupressure Bands or Other Devices (1
Study) Nordio & Romanelli 2008 [81]
Not Reported Method(s): Acupressure at Therapeutic Acupoints using Wrist Acupressure Device, Selected Acupoint(s):
(Bilateral): Shenmen (HT7)
Method(s): Acupressure at Non-Therapeutic (Irrelevant) Acupoints using Wrist Acupressure Device, Selected Acupoint(s):
(Bilateral): Acupoint Known as not to Interfere with Insomnia and/or Anxiety (Details not Described)
Total Duration: 20 Days Equal for Both TA
and SA
doi:10.1371/journal.pone.0132989.t003
Sham Acupressure Controls Used in Randomized Controlled Trials
the interior surface which can exert constant pressure at the targeted acupoint. However, in one study [40], the
button was replaced by a backing square in the sham group. In two trials where the non-acupoints located at the
forehead, adhesive beads were applied [41, 44]. Special band was also adopted on the non-acupoint located below
the knee in one study [35], and mag- netic suction cup was utilized in another trial to stimulate the non-acupoints on
both hands [38]. Particularly, a dentist’s tool was employed for acupressure in one trial which selected more than ten
non-acupoints [54]. Twenty studies described the definite locations of the non- acupoints. Most of the studies with
type 2 design adopted equal acupressure intensity between groups, while it was unequal in four trials [35, 40, 52, 54]
with sham groups receiving lower- intensity pressure or no stimulation at all.
In 21 articles, the sham study arms employed the same acupoints as in the true acupressure arms. Manual light
touch was applied in seven trials without any pressure (type 3) whereas the other 14 used a placebo device but also
no pressure was exerted (type 4). The intervention pro- tocols were all similar between groups except for the
acupressure intensity. For studies utilizing type 4 sham procedures, pseudo devices used in the control groups were
identical from those applied in true acupressure with the only exception that the pressure button was missing, or was
replaced by a blunted/flat one, or was located at the exterior of the equipment. One study stated that a dummy band
was applied but no detailed information was given [66].
Non-therapeutic acupoints were chosen as sham intervention in five trials. Of which, four utilized manual
acupressure (type 5) [77–80] and one employed a wrist acupressure device (type 6) [81]. In studies with type 5 sham
method, the intervention protocol was similar between groups in 3 studies [78–80], but in another trial [77], the
acupressure intensity was unequal between groups with the true intervention group applying a wrist band to create
con- stant pressure while the sham comparison received manual acupressure with discontinuous stimulation. The
only one article with type 6 sham procedure focused on insomnia [81]. Unfor- tunately, this study failed to specify
the selected sham acupoints but only stated that the irrele- vant acupoints were “known as not to interfere with” the
treated condition [81].
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 26 / 40
Table 4. Summary of the Therapeutic Outcomes based on Different Sham Acupressure Types.
Results of Therapeutic Effects
Types of Sham Control
No. of
SAG is Superior to
Studies
TAG4
Type 1 18# 13 (72.2%) 1 (5.6%) 4 (22.2%) 0 (0%) Type 2 20## 11 (55.0%) 3 (15.0%) 6 (30.0%) 0 (0%) Type 3 7 7 (100.0%) 0
(0%) 0 (0%) 0 (0%) Type 4 14 5 (35.7%) 4 (28.6%) 3 (21.4%) 2 (14.3%) Type 5 4 4 (100.0%) 0 (0%) 0 (0%) 0 (0%) Type 6 1 1
(100.0%) 0 (0%) 0 (0%) 0 (0%) Total 64 41 (64.1%) 8 (12.5%) 13 (20.3%) 2 (3.1%)
Type 1: Sham acupressure at non-acupoints by manual pressure; Type 2: Sham acupressure at non-acupoints by employing
acupressure devices; Type 3: Pseudo-intervention at the same acupoints as true treatment arm by manual light-touch; Type 4:
Pseudo-intervention at the same acupoints as true treatment arm by using placebo devices; Type 5: Manual acupressure at
non-therapeutic (irrelevant) acupoints; Type 6: Sham acupressure at non- therapeutic (irrelevant) acupoints by adopting
acupressure devices 1: For studies reporting multiple main outcomes, at least one “++” were identified 2: For studies reporting
multiple main outcomes, no “++” but at least one “+” were identified 3: “0” for all main outcome(s) 4: “−” or “− −”for all main
outcome(s) #: Sham acupressure control type 1 was applied in 19 studies, but comparison between groups was not performed (or
not clearly reported) in one study ##: Sham acupressure control type 2 was applied in 21 studies, but comparison between groups
was not performed (or not clearly reported) in one study
doi:10.1371/journal.pone.0132989.t004
TAG is Significantly Superior
TAG is Superior to
No Difference between TAG to SAG1
SAG2
and SAG3
Sham Acupressure Controls Used in Randomized Controlled Trials
Therapeutic Effects of Acupressure
Therapeutic outcomes of acupressure are summarized in Tables 4 and 5. Meanwhile, results of the responder rate
ratio calculation are presented in Table 6.
Overall Assessment. Sixty-four studies reported treatment outcomes between the true and sham acupressure
groups. For the main outcomes, 64.1% (41/64) reported that true acupres- sure was significantly superior to sham
intervention, and 12.5% favored the true procedure but the difference did not reach statistical significance, while
there were 13 studies (20.3%) which found no difference between groups. In addition, the sham acupressure was
found to be more effective than true intervention in two trials (3.1%) [70, 74] with one even reaching statistical
significance [70]. Among all the included studies, 12 compared the effects of acupressure (true/sham) with the study
arms using standard methods of care. In four trials [23, 29, 32, 71], true acupressure was shown to be more effective
than sham treatment and/or standard care, while no difference was found between sham acupressure and standard
care. In another seven studies [26, 28, 45, 47, 51, 60, 64], both true and sham procedures were found to be superior
to conventional care with or without statistical significance, while one trial [53] found no differ- ence among groups.
Thirty-four articles which provided dichotomous data were included for calculating responder rate ratio, and the
majority (27 studies) supported the superiority of true acupressure compared with sham intervention, with the
responder rate ratio (as measured by RR) greater than 1.0.
Subgroup Analysis. Subgroup analysis was performed based on different sham alterna- tives (Table 4). Fourteen
out of 18 studies (77.8%) employing type 1 sham procedure favored true acupressure. For type 2 studies, 70%
(14/20) supported the superiority of the true interven- tion. Of the 14 studies using pseudo-acupressure devices (type
4), nine (64.3%) reported that true acupressure was more effective than sham control, three (21.4%) found no
difference between groups, and two (14.3%) favored sham acupressure. Number of studies for sham type
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 27 / 40
Table 5. Summary of the Therapeutic Outcomes based on Different Health Problems and Treatment Durations.
Results of Therapeutic Effects
Subgroups No. of
Studies
SAG is Superior to TAG4
Health Problem Peri-operative Nausea and Vomiting #
TAG is Significantly
TAG is Superior
No Difference between Superior to SAG1
to SAG2
TAG and SAG3
21 8 5 6 2
Nausea and Vomiting in Pregnancy
9 7 0 2 0
Labor Pain 5 5 0 0 0 Sleep Disturbances 5 4 0 1 0 Perioperative/Prehospital Pain 4## 3 0 1 0 Anxiety 3 3 0 0 0 Symptoms in
Patients with Respiratory Disorders
3 2 0 1 0
Motion Sickness 2### 1 1 0 0 Primary Dysmenorrhea 2 1 0 1 0 Chemotherapy-induced Nausea and Vomiting
2 1 0 1 0
Postoperative Gastrointestinal Function
2 2 0 0 0
Cancer-related Fatigue 1 0 1 0 0 Stress Reduction 1 0 0 1 0 Urodynamic Stress Incontinence 1 1 0 0 0 Traumatic Brain Injury 1 1
0 0 0 Women’s General Health 1 1 0 0 0 Cardiovascular Function in Stroke Survivors
1 1 0 0 0
Post MI-related Nausea and Vomiting
1 0 1 0 0
Treatment Duration Less than 1 Hour 12#### 10 0 2 0 More than 1 Hour but Less than 1 Day
13 7 3 3 0
More than 1 Day but Less than 1 Week
16 8 3 4 1
More than 1 Week 16 12 1 3 0
1: For studies reporting multiple main outcomes, at least one “++” were identified 2: For studies reporting multiple main
outcomes, no “++” but at least one “+” were identified 3: “0” for all main outcome(s) 4: “−” or “− −”for all main outcome(s); MI:
Myocardial infarction # Twenty studies for postoperative nausea and vomiting and one study for intra-operative nausea and
vomiting ## Perioperative/prehospital pain was observed in 5 studies, but comparison between groups was not performed (or not
clearly reported) in 1 study ### Motion sickness was observed in 3 studies, but comparison between groups was not performed
(or not clearly reported) in 2 studies #### Acupressure durations were less than 1 hour in 14 studies, but comparison between
groups was not performed (or not clearly reported) in 2 studies
doi:10.1371/journal.pone.0132989.t005
Sham Acupressure Controls Used in Randomized Controlled Trials
3, 5 and 6 were limited, but all supported the superiority of true intervention. Responder rate ratios were also
separately analyzed for different sham acupressure types and the true interven- tion groups were found to be more
effective than the sham comparisons in the majority of the analyzed trials within each sham acupressure control
(Table 6).
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 28 / 40
Table 6. Results of Response Rates for Studies Presenting Dichotomous Data.
Study Outcome# Definition of Response TAG (n/
N)
Relative Risk 95% CI
Type 1 Sham Acupressure at Non-Acupoints: Manual Acupressure Bertalanffy et al. 2004 Sympathetic Activity Peripheral
Vasodilation 46/50 2/50 23.00 [5.90, 89.64] Kober et al. 2002 Pre-Hospital Anxiety Anxiety Reduction 13/19 10/20 1.37 [0.80,
2.33] Type 2 Sham Acupressure at Non-Acupoints: Acupressure Bands or Other Devices Adib-Hajbaghery & Etri 2013
Postoperative Nausea Absence of Nausea 17/35 18/35 0.94 [0.59, 1.51]
Adib-Hajbaghery & Etri 2013
Postoperative Vomiting Absence of Vomiting 19/35 20/35 0.95 [0.63, 1.44]
Alessandrini et al. 2012 Neurovegetative Symptom Symptom Improvement 87/102 11/102 7.91 [4.50, 13.90] Soltani et al. 2011
Postoperative Nausea Absence of Nausea 44/50 31/50 1.42 [1.12, 1.80] Soltani et al. 2011 Postoperative Vomiting Absence of
Vomiting 40/50 27/50 1.48 [1.11, 1.98] Bao et al. 2011 Pain Intensity Less Severity Pain 36/37 32/40 1.22 [1.03, 1.43] Majholm
& Møller 2011 Postoperative Nausea Absence of Nausea 37/57 29/51 1.14 [0.84, 1.55] Majholm & Møller 2011 Postoperative
Vomiting Absence of Vomiting 43/58 38/52 1.01 [0.81, 1.27] Sinha et al. 2011 Nausea and Vomiting in
Delivery
Absence of Nausea and/or Vomiting 82/170 87/170 0.94 [0.76, 1.17]
Wang et al. 2008 Postoperative Nausea and
Vomiting
Absence of Nausea and Vomiting 21/26 18/26 1.17 [0.85, 1.60]
Turgut et al. 2007 Postoperative Nausea Absence of Nausea 34/50 18/50 1.89 [1.25, 2.86] Turgut et al. 2007 Postoperative
Vomiting Absence of Vomiting 37/50 21/50 1.76 [1.22, 2.54] Heazell et al. 2006 Length of Hospitalization Less than 4 Days in
the Hospital 29/40 22/40 1.32 [0.94, 1.85] Samad et al. 2003 Postoperative Nausea and
Vomiting
Absence of Nausea and Vomiting 25/25 25/25 1.00 [0.93, 1.08]
Alkaissi et al. 2002 Postoperative Nausea and
Vomiting
90/135 86/139 1.08 [0.90, 1.29]
Agarwal et al. 2000 Postoperative Nausea Absence of Nausea 82/100 80/100 1.02 [0.90, 1.17] Agarwal et al. 2000 Postoperative
Vomiting Absence of Vomiting 93/100 91/100 1.02 [0.94, 1.11] Harmon et al. 2000 Postoperative Nausea and
Vomiting
Absence of Nausea, Vomiting or Rescue Medicine
Absence of Nausea and Vomiting 30/47 16/47 1.88 [1.19, 2.95]
Harmon et al. 1999 Postoperative Nausea and
Vomiting
Absence of Nausea and/or Vomiting 42/52 30/52 1.40 [1.07, 1.83]
Alkaissi et al. 1999 Postoperative Nausea and
Vomiting
11/20 11/20 1.00 [0.57, 1.75]
Fan et al. 1997 Postoperative Nausea and
Vomiting
Absence of Nausea, Vomiting or Rescue Medicine Absence of Nausea and Vomiting 83/108 54/92 1.31 [1.07, 1.60]
Bayreuther et al. 1994 Morning Sickness Symptom Reduction 10/15 5/15 2.00 [0.90, 4.45] Type 3 Pseudo-Intervention at the
Same Acupoints as Intervention Group: Manual Light-Touch without Acupressure Kashanian & Shahali 2010
Cesarean Delivery No Need for Cesarean Delivery 54/60 35/60 1.54 [1.23, 1.94]
Hjelmstedt et al. 2010 Use of Analgesics No Need for Analgesics 36/71 37/71 0.97 [0.71, 1.34] Lee et al. 2004 Use of Analgesics
No Need for Analgesics 31/36 29/39 1.16 [0.92, 1.45] Type 4 Pseudo-Intervention at the Same Acupoints as Intervention Group:
Placebo Acupressure Devices Nilsson et al. 2015 Postoperative Nausea and
Vomiting
Absence of Nausea and Vomiting 24/43 31/52 0.94 [0.66, 1.33]
Molassiotis et al. 2013 Chemotherapy-induced Nausea No Nausea Experience 41/126 36/118 1.07 [0.74, 1.55] Molassiotis et al.
2013 Chemotherapy-induced
Vomiting
No Vomiting Experience 85/126 80/118 1.00 [0.84, 1.18]
Noroozinia et al. 2013 Postoperative Nausea and
Vomiting
Absence of Nausea and Vomiting 76/76 72/76 1.06 [1.00, 1.12]
(Continued)
Sham Acupressure Controls Used in Randomized Controlled Trials
SAG (n/ N)
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 29 / 40
Table 6. (Continued)
Study Outcome# Definition of Response TAG (n/
N)
Relative Risk 95% CI
Soltanzadeh et al. 2012 Postoperative Nausea Absence of Nausea 29/40 22/40 1.32 [0.94, 1.85] Soltanzadeh et al. 2012
Postoperative Vomiting Absence of Vomiting 32/40 25/40 1.28 [0.96, 1.70] White et al. 2012 Postoperative Nausea Absence of
Nausea 30/50 26/50 1.15 [0.81, 1.64] White et al. 2012 Postoperative Vomiting Absence of Vomiting 45/50 37/50 1.22 [1.01,
1.47] Ho et al. 2006 Intraoperative Nausea Absence of Nausea 20/55 16/55 1.25 [0.73, 2.15] Ho et al. 2006 Intraoperative
Vomiting Absence of Vomiting 43/55 40/55 1.07 [0.87, 1.33] Klein et al. 2004 Postoperative Nausea Absence of Nausea 50/75
50/77 1.03 [0.82, 1.29] Klein et al. 2004 Postoperative Vomiting Absence of Vomiting 63/75 62/77 1.04 [0.90, 1.21] Schultz et
al. 2003 Postoperative Nausea Mild Nausea 14/25 14/21 0.84 [0.53, 1.33] Dent et al. 2003 Post-MI Nausea and Vomiting
Absence of Nausea and Vomiting 55/95 48/98 1.18 [0.91, 1.54] Duggal et al. 1998 Postoperative Nausea Absence of Nausea
53/122 42/122 1.26 [0.92, 1.73] Duggal et al. 1998 Postoperative Vomiting/
Retching
Absence of Vomiting/Retching 72/122 66/122 1.09 [0.88, 1.36]
Lewis et al. 1991 Postoperative Vomiting Absence of Vomiting 9/31 9/33 1.06 [0.49, 2.33] Type 6 Sham Acupressure at
Non-Therapeutic Acupoints (Irrelevant): Acupressure Bands or Other Devices Nordio & Romanelli 2008 Melatonin Metabolite
Normal Melatonin Rhythm 13/18 5/15 2.17 [1.00, 4.68]
TAG: True acupressure group; SAG: Sham acupressure group; MI: Myocardial infarction #: Outcome used for response rate
estimation
doi:10.1371/journal.pone.0132989.t006
Table 7. Summary of Dropout Rate Reported in the Included Studies.
Number of Dropout/Sample Size (Dropout Rate, %)
Types of Sham Control No. of Studies# TAG SAG Total Chi-Squared Test
Type 1 15 51/457 (11.2%) 37/450 (8.2%) 88/907 (9.7%) χ2 = 2.233, df = 1, P = 0.135 Type 2 15 20/895 (2.2%) 24/882 (2.7%)
44/1777 (2.5%) χ2 = 0.435, df = 1, P = 0.509 Type 3 6 2/246 (0.8%) 4/246 (1.6%) 6/492 (1.2%) χ2 = 0.169, df = 1, P = 0.681
Type 4 10 64/729 (8.8%) 74/716 (10.3%) 138/1445 (9.55%) χ2 = 1.013, df = 1, P = 0.314 Type 5 2 6/46 (13.0%) 7/46 (15.2%)
13/92 (14.1%) χ2 = 0.090, df = 1, P = 0.765 Type 6 1 2/20 (10.0%) 5/20 (25.0%) 7/40 (17.5%) χ2 = 0.693, df = 1, P = 0.405
All Types 49 145/2393 (6.1%) 151/2360 (6.4%) 296/4753 (6.2%) χ2 = 0.234, df = 1, P = 0.629
Type 1: Sham acupressure at non-acupoints by manual pressure; Type 2: Sham acupressure at non-acupoints by employing
acupressure devices; Type 3: Pseudo-intervention at the same acupoints as true treatment arm by manual light-touch; Type 4:
Pseudo-intervention at the same acupoints as true treatment arm by using placebo devices; Type 5: Manual acupressure at
non-therapeutic (irrelevant) acupoints; Type 6: Sham acupressure at non- therapeutic (irrelevant) acupoints by adopting
acupressure devices # Number of studies which were available for dropout rate calculation
doi:10.1371/journal.pone.0132989.t007
Sham Acupressure Controls Used in Randomized Controlled Trials
SAG (n/ N)
Subgroup analyses were also applied for different types of health conditions and treatment duration (Table 5).
Descriptive analysis showed that true acupressure can be an effective approach in managing postoperative and
pregnancy-related nausea and/or vomiting, perioper- ative/prehospital pain, labor pain, sleep disturbances,
respiratory disorders, anxiety, postopera- tive gastrointestinal dysfunctions and motion sickness. Studies on primary
dysmenorrhea and chemotherapy-induced nausea and vomiting reported contradictory findings, where two stud- ies
[57, 77] supported the superiority of true acupressure, while another two [17, 64] stated no difference between
groups. Results from a single study indicated that the true intervention was
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 30 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
better than sham control in treating urodynamic stress incontinence [23], traumatic brain injury [24], cancer-related
fatigue [16] and myocardial infarction-related nausea and vomiting [71], and in maintaining women’s general health
[25] and stroke survivors’ cardiovascular functions [27]. The only study on stress reduction failed to prove the
superiority of true acu- pressure [20]. For each subgroup under “treatment duration”, more than half (68.75% to
83.3%) supported that true acupressure was more effective than sham intervention (Table 5). Further investigation
on acupressure frequency and intensity was not feasible due to insuffi- cient information and absence of available
data.
Dropout Rates and Adverse Events associated with Acupressure
In 26 studies, all the randomized subjects completed the study. Thirty-four studies reported participants’ dropout,
however, 11 of them only provided the total dropout number but failed to specify the number in each study arm [19,
32, 47, 51, 53, 62, 70, 72, 75, 79, 80]. Reasons for dropout were diverse and included changing treatment protocol,
refusing to continue with the study, suffering from adverse events, or death, etc. The total dropout rate was 6.2%,
with the true intervention groups 6.1% and the sham groups 6.4%. Dropout rates also varied signifi- cantly among
different sham alternatives. The lowest was found in type 3 trials, with the total dropout rate being 1.22% (true
acupressure 0.8% and sham comparison 1.6%). Chi-square tests showed that there was no difference of the dropout
rates between groups (Table 7).
There were 24 studies that observed potential adverse events associated with acupressure, among which, 13
reported no adverse events, and the other 11 reported acupressure device- related harm data including local swelling
and redness, discomfort and tenderness at the wrist, and paresthesia, etc. No serious adverse events were noted.
There was one study [67] that detected adverse events such as constipation, headache, fatigue and drowsiness, but
informa- tion was insufficient to judge whether these were caused by acupressure. No study assessed the causality
between the acupressure and the reported adverse events.
Discussion
This study analyzed 66 trials with six sham acupressure types. The findings indicated that “non-acupoint” was the
most frequently selected sham acupoint and an acupressure device was the commonly adopted approach for sham
intervention. Meanwhile, our findings supported that acupressure was a beneficial method in managing a variety of
health problems, and the effect was found to be more effective in true acupressure than that in sham procedure.
Because of the significant clinical heterogeneity among the included studies, the relationship between sham
acupressure methods and the treatment outcomes is not fully conclusive at this stage.
Our findings showed that true acupressure was more effective than sham acupressure, and the effect of sham
intervention was somewhat better than that in the standard care arms. These results support the specific benefits of
true acupoint stimulation, but also indicate that sham acupressure more or less produces some specific or
non-specific treatment effects. Sham acu- pressure may be associated with larger effects than control groups
adopting standard methods of care. Placebo effects of sham acupoint stimulation may be related to patients’
expectation of treatment, and ventral striatum and prefrontal cortex are commonly believed to be involved in the
activation of the reward system which contributes to a feeling of symptom improvement during intervention [82].
Previous studies indicated that “physical placebos”, including sham acupoint stimulation (e.g. acupuncture), could
result in larger effects over non-treatment arms than drug placebos [83, 84]. Reasons for the relatively larger effects
in sham acupoint stimula- tion are complicated, and from a psychological perspective, any forms of acupoint
stimulation could be viewed as an emotional focused therapy which more or less produces some treatment
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 31 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
effects [82]. However, whether the effects produced by sham acupoint stimulation are only non-specific placebo
effects or are mixed with any specific therapeutic benefits, we still cannot reach a definite conclusion at present.
Similar to the results from the descriptive analysis, the exploratory analysis of the responder rate ratios also
showed that true acupressure was more effective than sham comparisons regardless of the sham acupressure types.
However, these findings should be interpreted pru- dently because the responder rate ratio only provides a rough
summary of the study results, and the dichotomous data we used were not the main measures in some of the
analyzed trials. Meanwhile, even within the subgroup of each sham acupressure method, clinical heterogene- ities
(e.g. differences in the health conditions, patient characteristics, intervention duration and outcome measures, etc.)
were still considerable in the analyzed trials. In addition, the number of studies included within each subgroup was
quite imbalanced among the sham types, with type 2 and 4 respectively gathering more than 10 studies, whereas
other sham modalities only including no more than three studies.
In the analyzed studies, non-acupoint was the most frequently adopted sham acupoint approach used.
Non-acupoint is a popular sham modality because generally it would not create any therapeutic effects. However,
we are not sure whether all the so-called “non-acupoints” in our analyzed trials are real non-acupoints because only
few of them pointed out that the selected non-acupoints were situated away from the meridians, while in the
remaining studies, the relation between the non-acupoints and their nearest active acupoints and/or meridians was
not provided. Meanwhile, researchers should prudently select the non-acupoints because currently there are more
than 2000 established extra-points which are not linked with meridi- ans, and this cannot exclude the possibility that
the so called “non-acupoints” in some trials may be unintentionally therapeutic points in nature [85].
In addition to the non-acupoints, true acupoints were also commonly used as sham acu- pressure. The acupoints
were the same as the active intervention groups but were only provided with light tough or totally received no
stimulation. It is believed that light stimulation on the true acupoints would not activate the deqi sensation, and thus,
avoid the generation of specific treatment effects [6, 85]. But recent studies on pain concluded that light stimulation
on the skin could evoke the activity of the cutaneous afferent nerves and/or the insular region of the brain, and may
result in some augmented therapeutic benefits [4, 86]. Also, patients with pain conditions could experience similar
treatment effects when the selected true and sham acu- points located at the same or nearby myotome [4, 87]. Light
touch may not be a proper sham approach for studies on pain management. Also, light stimulation was deemed
inadequate to maintain blinding of the participants, especially for those with previous acupressure experi- ence.
Light touch does not exert additional pressure and avoids evoking the deqi sensation. When the intervention is
observed by participants, it may be easy for them to judge that they are not receiving the “true” acupressure.
Non-therapeutic acupoints were used as the sham intervention in five of the included stud- ies. Regarding to the
location of the non-therapeutic acupoint, it is recommended to be situated near the selected active acupoint to
achieve proper blinding, but is also required to avoid being on the same meridian as in the true intervention. In one
trial which focused on pre-hospital analgesia for patients with distal radius fracture, jianliao (TE14) was employed
as one of the sham acupoints, and acupressure intensity was equal in both groups [78]. However, this kind of sham
design might not be adequate enough because acupressure at any of the body acu- points could contribute to some
pain relieving effects. In the meantime, jianliao is mainly used for treating shoulder and back pain, although not
specific for distal radius fracture, stimulation of jianliao might somewhat produce some positive impact on the pain
management of the whole body. According to the “holism concept” of acupuncture theory, every single stimulation
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 32 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
of the acupoint could result in comprehensive responses of the human body and subsequently generate specific
and/or non-specific effects [85]. That is to say, pressing irrelevant acupoints may also create some treatment effects
for the targeted condition, especially when the sham intervention receives the same acupressure intensity as in the
active intervention arm.
Acupressure devices can be an adequate method for retaining blinding. In our analyzed studies, acupressure
bands with or without the pressure button were commonly incorporated as sham interventions. The same or identical
equipment used in both groups makes the blind- ing of participants and outcome assessors possible, and blinding of
care providers can also be achieved if they are not involved in the application of the acupressure devices. In type 2
sham designs, most of the trials employed acupressure equipment on non-acupoints and used the same acupressure
intensity as in the true intervention arms. However, as mentioned above, acupressure at non-acupoints might induce
some unexpected treatment effects, and thus makes the type 2 design more effective than its own placebo effects.
Type 4 designs with pseudo-devices could be viewed as a good sham mode because those do not apply additional
pressure to the selected acupoints which could minimize the potential therapeutic effects at a greater extend. Also,
the appearance looks indistinguishable from the true acupressure tools which could keep the blinding at a
satisfactory level, particularly for acupressure-naive partici- pants. Unfortunately, tools such as acupressure bands
currently are only applicable for acu- points located on the arms or legs, and when a study adopts too many
acupoints, using acupressure equipment nearly becomes impossible.
Participants’ dropout rates were similar between groups. Although reasons for dropout var- ied among trials, no
participants were reported dropping out because of being allocated to sham group. Meanwhile, this review found
that the type 3 control had the lowest dropout rate. However, the low rate seemed not to be caused by the sham
intervention itself but by the nature of the included health problems. Among the six studies with the type 3 sham
approach, more than half were studying pregnant women preparing for delivery and the acupressure only lasted
several minutes.
For studies that observed potential adverse events associated with acupressure, no such events were found in
more than half of the studies. Adverse events related to acupressure iden- tified in the remaining trials were
generally mild and transient. Reported adverse events were associated with acupressure devices, which were mostly
attributed to wearing of the equipment for a longer time. Loosening the bands temporarily during the intervention
could help to reduce the side effects to some extent. Acupressure seems to be a relatively safe approach for
acupoints-stimulation. However, it is noted that none of the included trials assessed the causal- ity between the
acupressure and the reported adverse events, and standard causality assessment tools (e.g. The WHO-Uppsala
Monitoring Centre System for Standardized Case Causality Assessment) were failed to be applied in the analyzed
studies, which make it difficult to judge whether these adverse events are really caused by the acupressure
intervention or not.
Some limitations were identified in the analyzed studies which could affect the reliability of our results. Firstly,
true and sham acupressure protocols were described unclearly in some studies. Relationship and distance between
the non-acupoint and the nearest meridian were seldom reported. Information on intervention frequency and
intensity were also provided insufficiently in some trials, which made the subgroup analyses on the acupressure
frequency and intensity impossible. Secondly, subjective outcomes were utilized in more than half of the articles,
which produced a possibility for exaggerating the treatment effects of the intervention, especially for studies with
inadequate blinding and/or allocation concealment [88]. Thirdly, methodological flaws still existed among studies.
Assessment of the credibility of blinding is essential in clinical trials for evaluating the successfulness of blinding
design, especially for tri- als with a placebo/sham control arm, as inadequate blinding could contribute to
performance
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 33 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
and/or detection biases, which could exaggerate the potential specific/non-specific treatment effects of the
placebo/sham intervention. However, credibility of blinding was not tested in all the trials, and for some studies to
which the blinding of care providers could have been achieved (e.g. studies using identical acupressure bands), such
a design also failed to be incor- porated. Moreover, Chinese syndrome differentiation was not employed to guide
subject recruitment, acupoint identification, and acupressure-technique selection in studies using Chi- nese
acupressure, which may downgrade the feasibility and reliability of the intervention proto- cols to some degree.
The study objective which focused on whether different types of sham procedure yield dif- ferent therapeutic
outcomes was difficult to achieve in this review as limited homogeneous data could be accessed for conducting
subgroup analysis on the same health condition within each sham acupressure modality. Descriptive analysis only
provided a preliminary summary of the therapeutic effects of acupressure. The exploratory analysis of the responder
rate ratio was unable to always be consistent with the finding drawn from the study main outcomes with con-
tinuous variables as responder rate ratio was only a rough estimation and dichotomous data were not the main
outcomes for some studies. Meanwhile, even within single sham alternative, trials still showed heterogeneity in a
number of aspects, such as the differences in patient char- acteristics, treatment duration and the outcome measures,
etc., all of which made the interpre- tation of results a difficult task. In addition, our findings at the current stage
could not evaluate whether there were any sham designs that had produced additional treatment effects over and
above their own placebo effects. Finally, although we have made efforts to locate as much eligi- ble studies as
possible, the final included studies were only in English and Chinese. Several arti- cles written in languages other
than English or Chinese were excluded, inevitably leading to some language bias.
Implications for Future Research and Practice
Verbal and non-verbal interactions between practitioners/researchers and participants should be pre-standardized to
avoid increasing participants’ expectations to the treatment which may exaggerate the non-specific psychological
effects of the treatment [89, 90]. In studies utilizing an acupressure device, it is suggested that researchers and care
providers are not involved in the application of acupressure equipment in order to retain satisfactory blinding.
Furthermore, it would be better for future studies to recruit participants without any previous experience in
acupressure. Acupressure-naive subjects do not have any experience of deqi sensation, which may increase the
chance of reaching successful blinding of participants [6]. To equalize the treatment expectations among
participants, if possible, participants’ characteristics such as educational background, religion, and lifestyle, etc.
should be kept similar at the baseline, as these elements are considered to be potential social-psychological factors
that could affect par- ticipants’ expectations to treatment [85].
Selection of the sham methods should be in accordance with the study objectives and the actual requirements of
the intervention and participants, as well as the nature of the disease being treated. For example, if a study intends to
test the specificity of some particular acu- points, the true and sham acupressure protocols should be the same with
the only difference in the selected acupoints. To minimize potential therapeutic effects of sham interventions and to
maintain a satisfactory blinding design, non-acupoints located near the targeted true acupoints are generally
recommended but the definite locations should be identified with caution, and an acupoint detector (a commonly
utilized device for accurately locating effective body/auricular acupoints) could be considered to distinguish
ineffective non-acupoints from active true acu- points. For acupressure intensity, future studies are suggested to
exert only light or no
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Sham Acupressure Controls Used in Randomized Controlled Trials
stimulation to the sham acupoints to prevent the generation of the deqi sensation. Particularly, acupoint stimulation
should be avoided in pain studies adopting sham acupressure. While for studies using single sham acupoints on
hands or legs, it is suggested to apply identical acupres- sure devices on the same acupoints as in the true
intervention groups without any stimulation.
To facilitate the blinding of participants and/or care providers, some methods could be con- sidered to prevent
them from observing the treatment procedure, for instance, letting partici- pants wear eye patches when
administering the intervention [91], or using bandages to cover the wrist bands during surgical acupressure trials.
Moreover, some studies also pointed out that the effects of acupoint stimulation can be reflected on the neural
activities in the limbic system and subcortical structures which provides a possible direction for future research to
use the functional magnetic resonance imaging (fMRI) to adequately evaluate sham procedures based on the neural
activities of the brain [92,93].
As subjective outcomes (e.g. questionnaire and visual analogue scale, etc.) could be affected by the participants’
expectations to treatment, which subsequently exaggerates therapeutic effects, future studies could consider
including some objective measures. Some scholars point out that instead of using the word of “sham” or “placebo”,
informing participants that the aim of study is to compare two different treatment procedures would be more
credible to reach a successful blinding of study subjects [2, 94]. This kind of incomplete informed consent may be in
debate for ethical reasons [2]. However, according to the results of a nested qualitative study within a RCT using
acupressure (both true and sham) for controlling chemotherapy-induced nausea, it was acceptable for the study
participants to receive this kind of consent process [94]. Meanwhile, from the findings of this review as well as other
studies on sham acupoint stimula- tion [92, 95], sham interventions can also contribute to symptom improvement,
and thus, it seems plausible to view the sham acupressure as a non-specific treatment approach in nature. Finally, the
methodological quality of future trial needs to be improved. More detailed informa- tion on the theoretical
background of the selection and identification of true and sham acu- points should be provided. Treatment duration,
number of sessions, and acupressure intensity should be described in detail in the acupressure protocols. Even if it is
difficult to incorporate blinding of the practitioner in manual acupressure trials, a double-blind design for both
partici- pants and outcome assessors is still possible. Credibility of blinding should also be tested to investigate the
successfulness of blinding design and subsequent to identify the potential risk of performance and/or detection
biases. Related guidelines such as the CONSORT [96] and STRICTA [97] guidelines should be followed in the
development and reporting of acupressure trials.
Conclusions
A great diversity of sham acupressure controls have been used in the literature. A solid conclu- sion whether
different sham alternatives are related to different treatment outcomes cannot be derived because of the significant
clinical heterogeneity among the analyzed trials. Based on the findings of this systematic review, non-acupoints are
generally recommended but the defi- nite locations should be identified with caution. For studies using single sham
acupoints on hands or legs, it is suggested to apply identical acupressure devices on the same acupoint as in the
active intervention without any stimulation. While for studies on pain, stimulation of sham acupoints should be
avoided.
Supporting Information
S1 File. PRISMA Checklist. (PDF)
PLOS ONE | DOI:10.1371/journal.pone.0132989 July 15, 2015 35 / 40
Sham Acupressure Controls Used in Randomized Controlled Trials
S2 File. Systematic Review Protocol. (PDF)
S1 Table. Selected Searching Strategies. (PDF)
S2 Table. Excluded Acupressure Trials due to High Risk of Bias. (PDF)
S3 Table. Risk of Bias Assessment of the Included Trials. (PDF)
Author Contributions
Conceived and designed the experiments: JYT LKPS AM. Performed the experiments: JYT TW. Analyzed the data:
JYT AM. Contributed reagents/materials/analysis tools: TW. Wrote the paper: JYT. Revised the manuscript: JYT
AM LKPS WT.
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