Effectiveness and safety of massage in the treatment of anxiety and depression in patients with cancer: A protocol for systematic review and meta-analysis

Abstract

Background:
Anxiety and depression, complications of cancer, are prevalent but often overlooked mental illnesses. Studies have demonstrated that massage therapy is useful in relieving anxiety and depression of cancer survivors. However, the mechanism is still unclear and no systematic review has provided sufficient evidence for the treatment. Therefore, this protocol is carried out to comprehensively evaluate the reliability of cancer patients with anxiety and depression treated by massage.

Methods:
We will systematically search the relevant literature from PubMed, Cochrane Library, EMBASE, Web of Science, Wanfang, Chongqing VIP, CNKI and Chinese Biomedical Literature Database from the establishment of the databases to June 1, 2020. In addition, we will only include randomized controlled trials about massage for cancer survivors with anxiety and depression, regardless of language and publication status. Two experienced researchers will separately screen the literature, collect data, analyze data and synthesize data using RevMan V.5.3 software. The quality of the included trials in the study will be assessed by the Cochrane bias risk assessment tool.

Results:
The protocol for the meta-analysis will systematically evaluate the reliability of massage therapy for cancer patients with anxiety and depression.

Conclusion:
This conclusion will provide an important basis for evaluating whether massage is reliable in treating cancer survivors who feel anxious and depressed.

Inplasy registration number:
INPLASY202060101.

Full text

Effectiveness and safety of massage in the
treatment of anxiety and depression in patients
with cancer
A protocol for systematic review and meta-analysis
Siyu Qin, MM
a
, Yuanyi Xiao, MM
a
, Zhenhai Chi, MM
b
, Daocheng Zhu, MM
b
, Pan Cheng, MM
a
,
Ting Yu, MM
a
, Haiyan Li, MM
a
, Lin Jiao, PhD
b,∗
Abstract
Background: Anxiety and depression, complications of cancer, are prevalent but often overlooked mental illnesses. Studies have
demonstrated that massage therapy is useful in relieving anxiety and depression of cancer survivors. However, the mechanism is still
unclear and no systematic review has provided sufficient evidence for the treatment. Therefore, this protocol is carried out to
comprehensively evaluate the reliability of cancer patients with anxiety and depression treated by massage.
Methods: We will systematically search the relevant literature from PubMed, Cochrane Library, EMBASE, Web of Science,
Wanfang, Chongqing VIP, CNKI and Chinese Biomedical Literature Database from the establishment of the databases to June 1,
2020. In addition, we will only include randomized controlled trials about massage for cancer survivors with anxiety and depression,
regardless of language and publication status. Two experienced researchers will separately screen the literature, collect data, analyze
data and synthesize data using RevMan V.5.3 software. The quality of the included trials in the study will be assessed by the
Cochrane bias risk assessment tool.
Results: The protocol for the meta-analysis will systematically evaluate the reliability of massage therapy for cancer patients with
anxiety and depression.
Conclusion: This conclusion will provide an important basis for evaluating whether massage is reliable in treating cancer survivors
who feel anxious and depressed.
INPLASY registration number: INPLASY202060101
Abbreviations: CI =confidence interval, RCTs =randomized controlled trials.
Keywords: anxiety, cancer, depression, massage, protocol, systematic review
1. Introduction
Cancer, a concerning public health problem, threatens the health
of human beings all over the world. There are 18.1 million new
cancer patients and 9.6 million cancer deaths in 2018.
[1]
Not only
the physical health of patients but also their mental health can be
significantly affected by a diagnosis of cancer.
[2]
Anxiety and
depression, complications of cancer, are prevalent but often
overlooked mental illnesses.
[3]
Many research have also shown
that the most common psychological states with cancer patients
are anxiety and depression.
[4–9]
Meanwhile, two-thirds of cancer
survivors with depression are often associated with significant
anxiety in the clinical.
[10]
Currently, a series of studies have
reported that anxiety and depression can produce some negative
effects on patients’quality of life (QOL), health expenditures,
continuity of treatment, and cancer survival.
[3,11,12]
Therefore, it
is very important to find more effective treatments alleviating
anxiety and depression symptoms of patients who have been
diagnosed with cancer.
At present, pharmacotherapy and psychotherapy, the main
treatment means for anxiety and depression of cancer survivors,
play an important role in improving these distressing emo-
tions.
[2,3,12,13]
However, antidepressants and anxiolytics may
bring a variety of adverse impacts such as headaches, addiction,
seizures, suicide, and interactions with anticancer treatments.
[13–
SQ and YX contributed equally to this work and should be considered as co-first
authors.
The authors have registered this protocol in the INPLASY network (No.
INPLASY202060101).
This study was supported by The National Natural Science Foundation of China
(Grant number: 81860877, 81660821); Jiangxi Provincial Science and
Technology Department Major Project Innovation Fund Project (Grant number:
20181BBG70047).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are
publicly available.
a
College of Acupuncture-Moxibustion and Tuina, Jiangxi University of Traditional
Chinese Medicine,
b
The Affiliated Hospital of Jiangxi University of Traditional
Chinese Medicine, Nanchang, China.
∗
Correspondence: Lin Jiao, Affiliated Hospital of Jiangxi University of Traditional
Chinese Medicine, Nanchang, China (e-mail: jl0809@126.com).
Copyright ©2020 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Qin S, Xiao Y, Chi Z, Zhu D, Cheng P, Yu T, Li H, Jiao L.
Effectiveness and safety of massage in the treatment of anxiety and depression
in patients with cancer: A protocol for systematic review and meta-analysis.
Medicine 2020;99:39(e22262).
Received: 19 August 2020 / Accepted: 20 August 2020
http://dx.doi.org/10.1097/MD.0000000000022262
Study Protocol Systematic Review Medicine®
OPEN
1

15]
Besides, the psychological intervention available to patients is
also limited due to the lack of providers and financial
resources.
[16]
So, it is extremely necessary to seek an alternative
treatment that is effective, cheaper, and safer. It is reported that
Complementary and Alternative Medicine interventions are used
by more than half of cancer patients to relieve related
symptoms.
[17]
Nowadays, massage which is 1 of the most widely
used complementary and alternative medicine therapies can not
only relieve cancer-related symptoms but also bring physical and
mental pleasure.
[18]
Massage, defined as a method of manipulating body tissue by
hand, has certain effects on the vessel, nerves, and muscle system of
the body.
[19]
Compared to pharmacotherapy and psychotherapy,
massage has unique advantages because of its non-invasive, low-
cost, and safety characteristics.
[20]
According to a report, in North
American medical centers, massage treatment as a supportive
treatment is gradually available for cancer survivors to improve
comfort level, lessen symptoms and related side effects.
[21]
Many
studies have found that massage can reduce muscle fatigue,
improve blood flow, relaxmood as well as relieve cancer symptoms
such as anxiety, depression, pain, and nausea.
[20,22–24]
Moreover,
the result which was published in the Journal of Clinical Oncology
(JCO) also demonstrated that massage could relieve anxiety and
depression of cancer survivors.
[25]
To our knowledge, there is no recent systematic review
discussing whether massage therapy is safe and effective in
treating anxiety and depression symptoms of patients who have
been diagnosed with cancer. Therefore, we perform this protocol
to comprehensively assess the effect of massage for cancer
patients who feel anxious and depressed.
2. Methods
2.1. Study registration
The registration number of this study is INPLASY202060101.
We will strictly perform this protocol by following the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
Protocol (PRISMA-P) statement guidelines.
[26]
2.2. Inclusion criteria for study selection
2.2.1. Type of studies. Only randomized controlled trials
(RCTs) about massage for cancer survivors with anxiety and
depression will be included. There are no restrictions on language
and publication status. In addition, non-RCTs, experience report,
reviews will not be included.
2.2.2. Types of Participants. All cancer patients feeling anxious
and depressed will be included. There are no limitations for age,
ethnicity, and gender.
2.2.3. Types of interventions
2.2.3.1. Experimental interventions. The experimental group
will only include massage therapies, which include reflexology,
acupressure, manual lymphatic drainage, tuina, general massage,
etc. There is no restriction on the types of massage, treatment
sites, treatment time, and the frequency.
2.2.3.2. Control interventions. The interventions of the control
group will include any therapies without massage, such as drugs,
psychotherapy, routine care, placebo, cupping therapy, acupunc-
ture, etc.
2.2.4. Types of outcome measures
2.2.4.1. Primary outcomes.
1. The State Anxiety Inventory.
2. The Center for Epidemiological Studies Depression scale.
2.2.4.2. Additional outcomes.
1. The Quality of Life Questionnaire Core 30 from the European
Organization for Research on Treatment of Cancer.
2. Any adverse events.
2.3. Search methods
RCTs relating to massage management for anxiety and
depression of cancer survivors will be retrieved from PubMed,
Cochrane Central Register of Controlled Trials, EMBASE, Web
of Science, Chinese Biomedical Literature Database, Wanfang
Database, Chongqing VIP Database and Chinese National
Knowledge Infrastructure from the establishment of the data-
bases to June 1, 2020. In addition, The Clinicaltrials.gov, Chinese
Clinical Trial Registry will also be carefully retrieved to obtain
unpublished or ongoing trial data. The detailed PubMed
searching strategy is listed in Table 1.
2.4. Data collection and analysis
2.4.1. Selection of studies. All searched literature will be
imported into EndNote software (V.X9) for removing duplicate
literature. The 2 researchers (SQ and YX) will independently read
the title and abstract to exclude irrelevant literature. After
preliminary screening, they will carefully read the full text to
determine whether the related studies are eventually included in
the protocol. Then, a cross-check will be conducted by 2
researchers (SQ and YX). Finally, if there is any disagreement
when the 2 researchers perform the above operation, it will be
discussed or resolved by the third researcher (LJ). The specific
literature screening flow chart will be presented in Figure 1.
2.4.2. Data extraction and management. Two researchers (SQ
and ZC) will separately extract the following informations by
using data extraction forms which have been prepared in
advance:
(1) Research Characteristics: Year of publication, Journal, title,
information of the author.
(2) Participants’basic information: Gender, age, course of the
disease, country, sample size, severity of anxiety, and
depression.
(3) Study methods: Randomization, allocation concealment,
blinding, result analysis method.
(4) Intervention: Operation name, treatment sites, treatment
time, course of treatment, and frequency.
(5) Outcomes measurement: Primary and secondary outcomes.
2.5. Evaluation of bias risk in included studies
Two experienced researchers (SQ and ZC) will separately assess
the quality of the trials using the Cochrane bias risk assessment
tool.
[27]
It includes 7 aspects: random sequence generation,
allocation concealment, blinding of participants and personnel,
blinding of outcome assessment, incomplete outcome data,
Qin et al. Medicine (2020) 99:39 Medicine
2

selective outcome reporting, and other bias. Each item can be
classified as high, low, and unclear risk bias levels. When the
items related to studies are not clear, we will contact the authors
to get the required information. It is necessary to consult the
third researcher (LJ) to make a reliable decision if there is any
controversy.
2.6. Data synthesis
The following data analysis will be performed using RevMan 5.3
software. When the measured outcomes are dichotomous data,
the risk ratio (RR) with 95% confidence interval (CI) will be
adopted. When the measured outcomes are continuous data,
Weighted Mean Difference (WMD) with 95% CI will be adopted
if we use the same measurement instrument. And the Standard-
ized Mean Difference (SMD) with 95% CI will be applied if we
use different measurement instruments. x
2
test and I
2
test will be
utilized to investigate the heterogeneity. When the heterogeneity
is considered to be not obvious (P>0.1 or I
2
<50%), we will
choose the fixed-effect model. On the contrary, when the
heterogeneity is considered to be obvious (P0.1 or I
2
≥50%),
the random-effect model will be chosen and the subgroup
analysis or sensitivity analysis will be conducted to seek potential
causes of intergroup heterogeneity. A descriptive analysis is
necessary to be carried out if the heterogeneity is too significant.
2.7. Management of missing data
If the data of the included studies are unclear or missing, we will
do our best to contact the related authors of the article to acquire
complete data. If the above way of obtaining data information is
unsuccessful, we will only use current data for the data analysis.
2.8. Subgroup analysis
If significant heterogeneity exists in the included trials, it is
necessary to perform a subgroup analysis to reduce heterogeneity
between groups based on differences in massage methods, course
of the disease, sample size, the severity of anxiety and depression,
and so on.
2.9. Sensitivity analysis
If necessary, sensitivity analysis will be performed to evaluate
whether the conclusions of the meta-analysis are stable or reliable
by excluding trials of low quality.
2.10. Assessment of reporting biases
Funnel plots will be adopted to detect the publication bias if the
included trials exceed 10. Egger test will be performed to analyze
the potential causes of publishing bias if the asymmetry exists in
the funnel plots.
2.11. Quality of evidence
The quality of evidence will be independently evaluated by 2
researchers using the Grading of Recommendations Assessment,
Development, and Evaluation (GRADE),
[28]
and will be assessed
into high, moderate, low, and very low levels.
2.12. Ethics and dissemination
In the study, patients’personal information is not involved, so
ethical approval is not necessary. Results from this protocol will
be disseminated in a peer-reviewed journal.
3. Discussion
Anxiety and depression, complications of cancer, seriously affect
the mental health of cancer patients. Even though drug therapy
and psychotherapy are effective in relieving anxiety and
depression, these treatments may have some side effects. Massage
as a complementary and alternative therapy has been widely used
to alleviate anxiety and depression symptoms of patients who
have been diagnosed with cancer, due to its non-invasive, safe,
and inexpensive features.
[20]
Studies have shown that massage
therapy can be effective in easing mood and reducing cancer-
related symptoms, including depression, anxiety pain, fatigue,
and so on.
[20,24,25]
However, its clinical mechanism of action is
still unclear and no systematic review has provided sufficient
evidence for this treatment. We hope that the results of this study
are useful to patients, clinicians, and health policymakers.
Table 1
Search strategy used in PubMed database.
Number Search items
#1 randomized controlled trial [pt]
#2 controlled clinical trial [pt]
#3 randomized [tiab]
#4 clinical trials as topic [mesh: noexp]
#5 randomly [tiab]
#6 trial [ti]
#7 OR/#1–#6
#8 animals [mh] NOT humans [mh]
#9 #7 NOT #8
#10 Neoplasms[Mesh]
#11 Neoplasm[All Fields)
#12 Neoplasia[All Fields)
#13 Tumor[All Fields)
#14 Cancer[All Fields)
#15 Malignancy[All Fields)
#16 Malignant Neoplasm[All Fields)
#17 Carcinoma[All Fields)
#18 Neoplas[All Fields)
#19 OR/#10–#18
#20 Massage[Mesh]
#21 Zone Therapy[All Fields)
#22 Massage Therapy[All Fields)
#23 Anmo[All Fields)
#24 Tuina[All Fields)
#25 Acupressure[All Fields)
#26 Manipulate[All Fields)
#27 OR/#20–#26
#28 Anxiety[Mesh]
#29 Hypervigilance[All Fields)
#30 Nervousness[All Fields)
#31 Social Anxiety[All Fields)
#32 Depression[Mesh]
#33 Depressions[All Fields)
#34 Depressive Symptom[All Fields)
#35 Emotional Depression[All Fields)
#36 OR/#28–#35
#37 #9 AND #19 AND #27 AND #36
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3

However, the study may have the following limitations: First,
significant heterogeneity may exist due to different massage
methods, different treatment sites, and time. Second, certain
language bias may be caused due to the absence of language
limitations.
Author contributions
Conceptualization: Siyu Qin, Yuanyi Xiao.
Data curation: Siyu Qin, Zhenhai Chi.
Formal analysis: Siyu Qin, Yuanyi Xiao.
Funding acquisition: Lin Jiao.
Methodology: Siyu Qin, Zhenhai Chi.
Software: Siyu Qin, Yuanyi Xiao.
Supervision: Lin Jiao.
Writing –original draft: Siyu Qin, Yuanyi Xiao.
Writing –review & editing: Lin Jiao.
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Records idenfied through
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Figure 1. Flow diagram of study selection process.
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