JTCM Journal of
Traditional Chinese Medicine
Meta Analysis
Acupuncture and moxibustion for malignant tumor patients with
psychological symptoms of insomnia, anxiety and depression: a
systematic review and Meta-analysis
MA Fangfang, ZHANG Hewei, LI Bingxue, CHENG Peiyu, YU Mingwei, WANG Xiaomin
MA Fangfang, Department of Acupuncture-Moxibustion, Tuina and
Rehabilitation, Kunshan Hospital of Traditional Chinese Medicine,
Kunshan 215300, China
ZHANG Hewei, Traditional Chinese Medicine Department, the First
Affiliated Hospital of Soochow University, Suzhou 215006, China
LI Bingxue, Department of General Surgery, Pancreatic Disease
Center, Research Institute of Pancreatic Diseases, Ruijin Hospital,
Shanghai Jiaotong University School of Medicine, Shanghai 200025,
China
CHENG Peiyu, YU Mingwei, WANG Xiaomin, Oncology
Department, Beijing Hospital of Traditional Chinese Medicine, Capital
Medical University, Beijing 100010, China
Supported by Beijing Municipal Science and Technology
Commission: Demonstration and Popularization of Traditional Chinese
Medicine Standardized Diagnosis and Treatment of Common
Complications of Malignant Tumors (No. Z191100008319006);
Beijing Postdoctoral Science Foundation: Clinical Study of Five
Elements Acupuncture and Moxibustion in Treatment of Tumor-
Related Insomnia (No. EE2019-22) and Key Medical Discipline of
Suzhou: Rehabilitation of Traditional Chinese Medicine (No.
Szxk201822)
Correspondence to: Prof. WANG Xiaomin, Oncology Department,
Beijing Hospital of Traditional Chinese Medicine, Capital Medical
University, Beijing 100010, China. wangxiaomin_bhtcm@126.com;
M.D. ZHANG Hewei, Traditional Chinese Medicine Department, the
First Affiliated Hospital of Soochow University, Suzhou 215006,
China. nhzhw@aliyun.com
Telephone: +86-18310863610
DOI: 10.19852/j.cnki.jtcm.20230313.001
Received: December 12, 2021
Accepted: April 27, 2022
Available online: March 13, 2023
Abstract
OBJECTIVE: To evaluate the efficacy and safety of
acupuncture and moxibustion therapy (AMT) for cancer-
related psychological symptoms (CRPS) of insomnia,
depression and anxiety.
METHODS: Seven databases were searched for
randomized controlled trials (RCT) comparing AMT to
routine care or conventional drug for alleviating CRPS of
insomnia, depression, and anxiety before April 2020. Two
independent reviewers performed the data extraction and
assessed the risk of bias.
RESULTS: A total of 30 RCTs involving 2483 cancer
patients were enrolled. The pooled analysis indicated that
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the treatment group was significantly better than the
control group in improving the depression effective rate
[RR = 1.29, 95% CI (1.12, 1.49), P = 0.0004], the quality
of life (QOL) [MD = 1.11, 95% CI (0.80, 1.42), P < 0.000 01],
and reducing Self-rating Anxiety Scale (SAS) [MD =﹣7.75,
95% CI (﹣10.44, ﹣5.05), P < 0.000 01]. But there was
no statistically significant difference between two groups
in improving the insomnia effective rate [RR = 1.18, 95%
CI (0.93, 1.51), P = 0.18]. The subgroup analysis showed
the effectiveness of different intervention on CRPS.
Compared with routine care, AMT helps relieve CRPS
better evaluated by Pittsburgh Sleep Quality Index (PSQI),
Hamilton Depression Scale (HAMD), and Self-rating
Depression Scale (SDS), and depression effective rate.
Compared with conventional drug, AMT performs better
evaluated by SDS, depression effective rate and QOL.
Moreover, the conventional drug showed higher
treatment efficacy on improving insomnia effective rate
compared with AMT. Compared to conventional drug,
AMT plus conventional drug resulted in a significant
reduction on CRPS such as PSQI, HAMD, SDS, and SAS,
and also had a meaningful improvement on insomnia
effective rate, depression effective rate and QOL. Fewer
published reports were found on the adverse events of
AMT than the conventional drug.
CONCLUSION: The results suggested that AMT might be
effective in improving CPRI; however, a definite
conclusion could not be drawn because the quality of
trials are low. Further large-scale and high-quality RCTs
to verify the efficacy and safety of AMT on CRPS are still
warranted.
© 2023 JTCM. All rights reserved.
Keywords: acupuncture; moxibustion; neoplasms; sleep
initiation and maintenance disorders; depression; anxiety;
review
1. INTRODUCTION
As one of the leading causes of morbidity and mortality
worldwide, cancer is steadily increasing in rate, resulting
in a huge global burden over the past 30 years. The global
442 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
cancer burden is expected to be 28.4 million cases in
2040, a 47% rise from 2020.1 Meanwhile cancer
survivors grow rapidly with ongoing therapy. More than
3% of the adult in Western countries have survived for
5 years as cancer cases. By 2022, 64% of 18 million
cancer cases in the United States are estimated to survive
5 years or more; 40% survive 10 years or more and 15%
survive 20 years or more after diagnosis.2 4.3 million new
cancer cases and 2.9 million new cancer deaths estimated
occurred in China in 2018,3 with 36.9% of cancer patients
surviving at least 5 years after diagnosis.4 Surviving
cancer patients generally suffer from various symptoms
and expect long-term survival as a chronic disease.5 On
account of cancer invasion or its treatment, cancer
treatments increase the risk for numerous late effects,
thus making cancer survivors psychologically and
medically vulnerable.6
Cancer-related psychological symptoms (CRPS)
includes highly prevalent symptoms like depression,
anxiety and insomnia with the overall prevalence at 30%-
40%.7-11 Untreated depression and ongoing insomnia are
associated with decreased immune responses and lower
survival rates.12 CRPS links to cancer incidence and
mortality risk, which presented a negative correlation
with the quality of life (QOL) and positive correlation
with physical symptoms.13-15 Failing to identify and treat
CRPS promptly may lead to serious consequences on
QOL in cancer patients,16 which can be alleviated with
appropriate interventions.
There are at risk for antidepressant, anxiolytic and
hypnotic use up in five years after the diagnosis of cancer
patients.17 However, pharmacological treatments of
CRPS are not curative and in the meanwhile they often
result in additional side effects (dizziness, residual
daytime sedation, fatigue, daytime sleepiness, and
headache).18, 19 With the study of drug-drug interaction
between antidepressants and cancer treatment, direct
consequences have shown that patients on tamoxifen and
antidepressant have doubled the risk of relapse to cancer
in two years.12 Financial distress is also an important and
common factor contributing to the suffering of advanced
cancer patients and their caregivers.20 Therefore cancer
patients and providers alike are interested in evidence-
based nonpharmacologic alternatives like acupuncture
and moxibustion to relieve these symptoms.
Acupuncture is performed by taking fine needles to insert
in the acupoints and stimulate needling response, either
manually or electrically, to treat side effects of
conventional cancer treatment. Moxibustion involves
burning the moxa on or above the skin at acupoints with
stick-on moxa, sandwiched moxibustion or indirect
moxibustion.21 Acupuncture and moxibustion therapy
(AMT), originated from the system of Traditional
Chinese Medicine, has been in use at least 2500 years in
China and other Asian countries.21 AMT has a good
effect on CRPS and is easy to operate, safe, and
economical. National Cancer Institute (NCI) have
recommended “Acupuncture for Cancer Symptom
Management” to target common symptom clusters such
as pain, sleep disturbance, fatigue, chemotherapy side
effects, psychological distress, and impairment in quality
of life.22-29 As effective interventions, acupuncture and
moxibustion have been confirmed to improve financial
distress and relieve the effect of CRPS on the quality of
life of advanced cancer patients.22
Although three published reviews have reported the effects
of acupuncture and moxibustion on CRPS,30-32 there is no
Meta-analysis of AMT on CRPS. Meanwhile the included
studies in the three published reviews are in low quality
without enough recent studies. With the rapid development
in recent years, more related studies with high quality have
been published. Therefore, this study aims to screen recent
studies on that issue for a systematic review and Meta-
analysis, thus examining the clinical efficacy and safety of
AMT on CRPS of insomnia, anxiety and depression
systematically.
2. METHODS
Protocol register
The protocol for this systematic review was registered in
the Prospective Register of Systematic Reviews
(PROSPERO): CRD42020197084.
Search strategy
The following databases were searched from their
inception until April 15, 2020: PubMed, EMBASE,
Cochrane Library, China National Knowledge
Infrastructure Database (CNKI), China Science and
Technology Journal Database (VIP), Chinese
Biomedical Literature Database (CBM) and Wanfang
Database. The complete manuscripts of all relevant
studies published in English and Chinese were retrieved.
The search terms included (acupuncture OR single
needle OR electric acupuncture OR blood-letting
puncture OR head acupuncture OR scalp acupuncture
OR ear needle OR auricular acupuncture OR dermal
needle OR acupoint catgut embedding OR fire needle
OR meridian OR acupotomy OR moxibustion method
OR moxibustion OR direct moxibustion OR indirect
moxibustion OR heat-sensitive moxibustion OR needle
warming moxibustion OR ginger-separated moxibustion
OR salt-separated moxibustion) AND (cancer OR
tumour OR neoplasms OR malignancy OR carcinoma)
AND (sleep disorder OR sleep disturbance OR insomnia
OR depression OR depressive disorder OR anxiety).
Inclusion and exclusion criteria
2.3.1 Types of studies
To collect evidence of high quality, only randomized
controlled trials (RCTs) were included in this systematic
review. Only full articles were included.
2.3.2 Types of participants
The participants who were diagnosed with the
psychological symptoms like insomnia, anxiety and/or
depression due to interior-stirring by cancer would be
 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
included. Additionally, patients with mental disorders
would be excluded. Serious organic disease and
complications or pregnancy would not be considered.
2.3.3 Types of intervention
All of the cancer patients with psychological symptoms
were required to undergo basic cancer treatment in both
the treatment and control groups.
Treatment interventions. In the treatment group, the
intervention would be AMT combined with/without
conventional drug or routine care. These included studies
could perform the forms of acupuncture (e.g., manual
acupuncture, electro-acupuncture, intradermal needling
and scalp-acupuncture) and/or moxibustion (e.g., direct
or indirect moxibustion, heat-sensitive moxibustion,
warm needling, ginger-separated moxibustion or salt-
separated moxibustion). The other forms of AMT, such
as acupressure, transcutaneous electrical nerve
stimulation, point injection, laser irradiation, far infrared
moxibustion, auricular acupressure, auricular
acupuncture and cupping would be excluded.
The conventional drug would be the regular and frequent
use on the treatment of insomnia, depression, and anxiety
of CRPS such as paroxetine, sertraline, diosmin tablets,
estazolam or diazepam. The routine care included
nursing intervention, explanation of disease knowledge,
life guidance and psychological health education.
Control interventions. In the control group, the patients
would receive conventional drug or routine care that
prevent the psychological symptoms like insomnia,
anxiety and/or depression. Placebo controls or sham
acupuncture for the purpose of blinding are encouraged.
The following treatment comparisons would be studied:
Acupuncture and/or moxibustion compared with routine
care;
Acupuncture and/or moxibustion compared with
conventional drug;
Acupuncture and/or moxibustion plus conventional drug
compared with conventional drug.
2.3.4 Types of outcomes
2.3.4.1 Primary outcomes
(a) the effective rate of the psychological symptoms like
insomnia, anxiety or depression.30-32
The effective rate of insomnia was used to assess the
sleep effectiveness. Recovery: sleep time returned
normal or more than 6 h a night, with deep sleep and
wake up energetically; Remarkable effect: sleep quality
was obviously improved with sleep time and depth sleep
increased; Effective: sleep quality was improved but
some symptoms still existed; Invalid effect: no
significant improvement or reverse aggravation of
insomnia after treatment. The effective rate of insomnia
= recovery rate + marked effective rate.
The HAMD reduced rate was used to assess the
therapeutic effectiveness as the effective rate of
depression. HAMD reduced rate (%) = (score before
treatment-score after treatment) /score before treatment
443
× 100%, cure rate (reduced rate > 75%), effective rate
(reduced rate 50%-75%), improved rate (reduced rate
25%-49%), invalid rate (reduced rate < 25%). The
effective rate of depression = recovery rate + marked
effective rate.
(b) Scales or indices for the quality evaluation of the
psychological symptoms like insomnia, anxiety or
depression, the Pittsburgh Sleep Quality Index (PSQI),
Hamilton Depression Scale (HAMD), Self-rating
Depression Scale (SDS), Self-rating Anxiety Scale
(SAS).
2.3.4.2 Secondary outcomes
The secondary outcomes of this review mainly included
the quality of life (QOL) and adverse events.
Selection of studies and data extraction
Two authors (MA Fangfang and LI Bingxue) screened
all the records independently and abstracted all related
data from the enrolled papers, including first author’s
name, country, year of publication, age, gender, sample
size, diagnosis standard, details of interventions for
treatment groups and control groups, cointerventions,
outcome measures, treatment duration, and adverse
events. Disagreements were resolved by discussion or
consulting a senior researcher (WANG Xiaomin).
Quality assessment
The methodological quality was assessed according to
the Cochrane Handbook version 5.3. Two authors (MA
Fangfang and LI Bingxue) independently extracted the
data from the included studies. The risk of bias quality
was assessed based on 7 domains: random sequence
generation, allocation concealment, blinding of
participants and personnel, blinding of outcome
assessment, incomplete outcome data, selective
reporting and other bias. There were three potential bias
judgments according to the Cochrane criteria after
assessing all the domains: (a) low risk; (b) high risk; and
(c) unclear risk. Disagreements were resolved by
discussion between all of the authors.
Statistical analysis
For dichotomous data, we present the treatment effect as
relative risk with 95% confidence intervals (CIs). For
continuous data, we used the mean difference (MD) with
95% CIs to measure the treatment effect. In the case of
outcome variables with different scales, we used the
standardized mean difference (SMD) with 95% CIs. The
χ2 test for heterogeneity and the I2 test were used to
evaluate the heterogeneity of the included studies. When
P ≥ 0.10, I2 ≤ 50%, there was no statistical
heterogeneity between the results included in the study
and the fixed effect model was used for analysis. If P <
0.10, I2 > 50%, it was considered as statistically different.
Then we made an analysis on the heterogeneity sources
to determine whether the sensitivity analysis and
subgroup analysis were needed, whether random effects
models can be used for analysis or not. Descriptive
444 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
analysis was used if the clinical heterogeneity was too
large or the literature was too few to perform Meta-
analysis. Methodological quality evaluation was
performed by the bias risk map drawn by Revman 5.3
software (Cochrane Library, London, UK). When there
were more than 10 articles on a certain outcome indicator,
an inverted funnel plot was used to assess the published
bias of the included study. All the analyses were done
using Revman 5.3.
3. RESULTS
Literature Search Results
A total of 2474 studies were retrieved at the initial search.
After removing 799 duplicates, 1675 studies were
identified for further analysis. Through screening the
titles and abstracts, 1615 studies were excluded because
they were literature reviews, expert opinions,
commentaries, case reports, case series, nonclinical
studies, animal research or irrelevant intervention. Of the
remaining 60 studies, by reading the full text, 30 studies
met our inclusion criteria, as shown in Figure 1.
Characteristics of included studies
The basic characteristics of the included studies are listed
in Table 1.33-62 By integrating the 30 included studies, a
total of 2483 cases were reported with 1235 cases in the
treatment group and 1248 cases in the control group. The
Figure 1 Flow diagram of studies included in the review
CNKI: China National Knowledge Infrastructure Database; VIP: China Science and Technology Journal Database; CBMdisc: China Biology
Medicine disc; EMbase: Excerpt Medica Database; RCT: randomized controlled trial.
publication period was from 2008 to 2020. One study
was published in English and the other 29 studies were
published in Chinese. Six studies were for female breast
cancer patients. All of the included patients were
concentrated in China with a wide variation in the age of
subjects (18-80 years). All studies included at least one
of the main outcome indicators, which corresponding to
the diagnosis standards of the psychological symptoms
like insomnia, anxiety and/or depression due to interior-
stirring by cancer.
We divided the studies into three subgroups according to
their different treatment comparisons. The first subgroup
was AMT versus routine care in 8 studies;33,40,41,44,50-52,55
the second subgroup was AMT versus conventional drug
(CD) in 11 studies;35,42,45,46,48,49,54,56,59,61,62 the third
subgroup was AMT plus CD versus CD in 11 studies.34,
36-39,43,47,53,57,58,60
Total treatment sessions ranged from 7
d to 12 weeks, and intervention time ranged from 30 to
60 min.
Risk of bias
According to the Cochrane Handbook for Systematic
Reviews of Interventions, we assessed the risk of bias of
the included literature. The details of the risk of bias
(ROB) assessment in 30 studies are provided in Figure 2.
19 RCTs described the appropriate random sequence
generation method in detail while the other 11 studies did
not. 19 studies using allocation concealment with sealed
Table 1 Basic characteristics of the included studies
Study Sample Age year Gender Disease diagnosis Control Intervention Main treated acupoints and treatment frequency Course Outcome
size (T/C) (Male measure
(T/C) /Female)
Chen YH 30/30 T: 38-83 T: 18/12 Gastric cancer Routine care Moxibustion+C MT: Zusanli (ST36), Xuehai (SP10), Sanyinjiao (SP6) and Zhongwan (CV12). 2 w SDS, SAS
et al C: 24-82 C: 20/10 +anxiety and 1 time per day for 30 min
201333 depression
Chen J 18/18 T: 66.43±5.43 T: 10/8 Tumor+depression Paroxetine 20-60 Acupuncture AT: Neiguan (PC6), Shenmen (TF4), Yifeng (SJ17), Baihui (GV20), 6w HAMD,
201834 C: 65.13±5.98 C: 9/9 mg/d+anti-tumor +moxibustion+c Sishencong (EX-HN1), Hegu (LI4) and Taichong (LR3). depression
therapy 1 time per day for 30 min efficiency
MT: Guanyun (CV4) and Zusanli (ST36).
1 time per day for 30 min
Dan ZJ 27/28 T: T: 14/13 Tumor+insomnia Estazolam 1mg/d Acupuncture AT: Baihui (GV 20), Shenting (GV24), Yintang (EX-HN3), Shenmen (TF4), 7d Sleep
201335 52.222±7.153 C: 16/12 +boxed Zusanli (ST36) and Sanyinjiao (SP6). efficiency,
C: moxibustion PSQI
51.296±6.866 MT: Shenque (CV8) and Guanyun (CV4).

Deng XY 30/30 T: 48.93±4.03 T: 12/18 Tumor+depression Sertraline 10 mg/d+ Acupuncture+Elec AT: Yinlingquan (SP9), Fenglong (ST40), Hegu (LI4), Neiguan (PC6), 4w HAMD,
et al C: 50.13±4.09 C: 16/14 anti-tumor therapy tric acupuncture Taichong (LR3), Sanyinjiao (SP6), Yintang (EX-HN3) and Baihui (GV 20). QLQ-C30
201836
EA: Yinlingquan (SP9) and Fenglong (ST40).

Deng XY 30/30 T: 53±9 T: 11/19 Tumor+depression Sertraline 50 mg/d Acupuncture+C AT: Hegu (LI4), Taichong (LR3), Neiguan (PC6), Shenmen (TF4), Zusanli 4w HAMD,
et al C: 49±11 C: 10/20 (ST36), Sanyinjiao (SP6), Yintang (EX-HN3) and Baihui (GV 20). QLQ-C30
201937 for 30 min
Feng Y et 40/40 T: 63.80±5.47 T: 26/14 Malignant Fluoxetine 20 mg/d Acupuncture+C AT: Fenglong (ST40), Yinlingquan (SP9), Xuehai (SP10), Sanyinjiao (SP6), 30 d SDS,
al 201138 C: 63.60±4.26 C: 27/13 neoplasms+insomni Yintang (EX-HN3), Baihui (GV 20), Sishencong (EX-HN1), Neiguan (PC6) HAMD,
a and depression and Shenmen (TF4). depression
efficiency,
PSQI
Feng XT 70/70 35-78 61/79 Liver Paroxetine 20 mg/d Acupuncture AT: the acupoints of liver meridian and heart meridian, Shenmen (TF4), 8w SDS, SAS
et al (61.51±6.24) cancer+anxiety and +chinese herb+c Danzhong (CV 17), Taichong (LR3), Qimen (LR14) and Xingjian (LR2).
201939 depression
Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456

Liao LL 35/34 T: T: 14/21 Tumor+insomnia Routine care Intradermal IN: Yintang (EX-HN3) and Shenmen (TF4). 2w PSQI
201940 63.63±16.30 C: 13/21 needling
C: +moxibustion MT: Zusanli (ST36) and Sanyinjiao (SP6).
63.18±15.04
Liu YL 30/30 T: 51.63±9.14 T: 10/20 Tumor+depression Routine care Thermal MT: Baihui (GV 20), Shenmen (TF4), Neiguan (PC6), Taichong (LR3) and 21 d HAMD,
201741 C: 54.63±9.89 C: 12/18 moxibustion Ganshu (BL18). depression
efficiency
445
 446

Table 1 Basic characteristics of the included studies (Continued)

Study Sample Age year Gender Disease diagnosis Control Intervention Main treated acupoints and treatment frequency Course Outcome
size (T/C) (Male measure
(T/C) /Female)
Liu XF et 40/40 T: Female Breast Diosmin tablets Needle warming Jianyu (LI15), Waiguan (SJ5), Yinlingquan (SP9), Quchi (LI11), Shuifen 28 d SDS,
al 201942 46.37±14.53 cancer+anxiety and 2.7 g/d moxibustion (IN9) and Zusanli (ST36). SAS,
C: depression QLQ-C30
49.32±13.22
Liu YP et 40/40 T: 63±13 T: 24/16 Tumor+depression Escitalopram 10 Acupuncture+C AT: Taichong (LR3), Hegu (LI4), Baihui (GV 20) and Yintang (EX-HN3). 12 w HAMD
al 201943 C: 63±12 C: 20/20 -20 mg/d 5
Mo ZY et 58/60 T: Female Breast Routine care Ginger moxi- MT: Hegu (LI4), Zusanli (ST36), Taichong (LR3) and Yongquan (KI1). 7d SDS, SAS
al 201744 48.22±10.28 cancer+anxiety and bustionwithbox
C: depression
48.60±11.02
Pei Y et 31/36 T: Female Breast Citalopram 20 mg/d Acupuncture AT: Feishu (BL13), Xinshu (BL15), Geshu (BL17), Ganshu (BL18), Pishu 6w SDS,
al 201045 51.76±10.21 cancer+anxiety and (BL20) and Shenshu (BL23). SAS,
C: 48.34±8.79 depression HAMD
Peng XH 93/97 T: T: 68/36 Tumor+insomnia Estazolam 1 mg/d Acupuncture AT: Baihui (GV 20), Shenting (GV24), Yintang (EX-HN3), Shenmen (TF4), 7 d Sleep
et al 59.36±12.54 C: 68/36 +moxibustion Zusanli (ST36) and Sanyinjiao (SP6). efficiency
201746 C:
60.95±11.11 MT: Shenque (CV8) and Guanyun (CV4).

Shen LP 50/50 T: 54. T: 28/22 Lung Zolpidem 10 mg/d+ Acupuncture+Elec AT: Zhaohai (KI6), Shenmai (BL62), Shenmen (TF4), Yintang (EX-HN3), 4w SDS,
et al 93±14.45 C: 31/19 cancer+insomnia Paroxetine 20 mg/d tric Sishencong (EX-HN1), Anmian(Extra 8), Hegu (LI4), Taichong (LR3), SAS,
201647 C: 58. (if needed) acupuncture+C Zusanli (ST36), Qihai (CV6) and Quchi (LI11). PSQI
09±12.11
EA: Shenmen (TF4), Anmian(Extra 8), Sishencong (EX-HN1), Hegu (LI4),
Taichong (LR3), Zusanli (ST36), Qihai (CV6) and Quchi (LI11).

Shi Y et 40/40 NR NR Tumor+insomnia Diazepam 5 mg/d Scalp-acupuncture AT: Baihui (GV 20), Sishencong (EX-HN1). 7d PSQI
al 201448
SA: Ezhongxian (MS2~3).

Song JR 60/60 NR NR Tumor+insomnia Estazolam 1 mg/d Acupuncture AT: Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), Shenmen (TF4), 7d Sleep
et al boxed Zusanli (ST36) and Sanyinjiao (SP6). efficiency,
Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456

201549 moxibustion PSQI

MT: Shenque (CV8) and Guanyun (CV4).

Liu XF et 40/40 T: Female Breast Diosmin tablets Needle warming Jianyu (LI15), Waiguan (SJ5), Yinlingquan (SP9), Quchi (LI11), Shuifen 28 d SDS, SAS,
al 201942 46.37±14.53 cancer+anxiety and 2.7 g/d moxibustion (IN9) and Zusanli (ST36). QLQ-C30
C: depression
49.32±13.22
Liu YP et 40/40 T: 63±13 T: 24/16 Tumor+depression Escitalopram 10- Acupuncture+C AT: Taichong (LR3), Hegu (LI4), Baihui (GV 20) and Yintang (EX-HN3). 12 w HAMD
al 201943 C: 63±12 C: 20/20 20 mg/d 5
Table 1 Basic characteristics of the included studies (Continued)
Study Sample Age year Gender Disease diagnosis Control Intervention Main treated acupoints and treatment frequency Course Outcome
size (T/C) (Male measure
(T/C) /Female)
Mo ZY et 58/60 T: Female Breast cancer+ Routine care Ginger moxi- MT: Hegu (LI4), Zusanli (ST36), Taichong (LR3) and Yongquan (KI1). 7d SDS, SAS
al 201744 48.22±10.28 anxiety and bustionwithbox
C: depression
48.60±11.02
Pei Y et 31/36 T: Female Breast Citalopram 20 mg/d Acupuncture AT: Feishu (BL13), Xinshu (BL15), Geshu (BL17), Ganshu (BL18), Pishu 6 w SDS, SAS,
al 201045 51.76±10.21 cancer+anxiety and (BL20) and Shenshu (BL23). HAMD
C: 48.34±8.79 depression
Peng XH 93/97 T: T: 68/36 tumor+insomnia Estazolam 1 mg/d Acupuncture AT: Baihui (GV 20), Shenting (GV24), Yintang (EX-HN3), Shenmen 7d Sleep
et al 59.36±12.54 C: 68/36 +moxibustion (TF4), Zusanli (ST36) and Sanyinjiao (SP6). efficiency
201746 C:
60.95±11.11 MT: Shenque (CV8) and Guanyun (CV4).

Shen LP 50/50 T: 54. T: 28/22 Lung Zolpidem 10 mg/d+ Acupuncture+Ele AT: Zhaohai (KI6), Shenmai (BL62), Shenmen (TF4), Yintang (EX-HN3), 4 w SDS, SAS,
et al 93±14.45 C: 31/19 cancer+insomnia Paroxetine 20 mg/d ctric Sishencong (EX-HN1), Anmian(Extra 8), Hegu (LI4), Taichong (LR3), PSQI
201647 C: 58. (if needed) acupuncture+C Zusanli (ST36), Qihai (CV6) and Quchi (LI11).
09±12.11
EA: Shenmen (TF4), Anmian(Extra 8), Sishencong (EX-HN1), Hegu
(LI4), Taichong (LR3), Zusanli (ST36), Qihai (CV6) and Quchi (LI11).

Shi Y et 40/40 NR NR Tumor+insomnia Diazepam 5 mg/d Scalp- AT: Baihui (GV 20), Sishencong (EX-HN1). 7d PSQI
al 201448 acupuncture
SA: Ezhongxian (MS2-3).

Song JR 60/60 NR NR Tumor+insomnia Estazolam 1 mg/d Acupuncture AT: Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), Shenmen 7d Sleep
et al boxed (TF4), Zusanli (ST36) and Sanyinjiao (SP6). efficiency,
201549 moxibustion PSQI
MT: Shenque (CV8) and Guanyun (CV4).

Wang Y 40/40 NR Female Breast Routine care Five-element The acupoints according to five-element acupuncture therapy. 6w SDS, SAS
201550 cancer+anxiety and acupuncture+
depression wheat grain
Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456

moxibustion
Wang 40/40 T: 52.47±9.62 Female Breast Routine care Intradermal IN: Shenmen (TF4), Sanyinjiao (SP6), Anmian (Extra 8), Zusanli (ST36) 4w PSQI
BN et al C: 50.16±7.34 cancer+insomnia needling and Taibai (SP3).
201951 5 times per week; 3 times per day (acupressing 1 min per point)

Wang 40/40 T: 39.52±8.35 T: 24/16 Brain tumor+ Routine care Acupuncture AT: Neiguan (PC6), Renzhong (GV26), Sanyinjiao (SP6), Chize (LU5), 4w SDS, SAS
WG et al C: 39.36±9.27 C: 22/18 Depression Jiquan (HT1), Fengchi (GB20), Weizhong (BL40), Tianzhu (BL10) and
202052 Wangu (BL12).
447
 448

Table 1 Basic characteristics of the included studies (Continued)

Study Sample Age year Gender Disease diagnosis Control Intervention Main treated acupoints and treatment frequency Course Outcome
size (T/C) (Male measure
(T/C) /Female)
Wei S 33/33 49.21±6.32 Female Gynecological Alprazolam Thunder-fire MT: Shenmen (TF4), Neiguan (PC6), Sanyinjiao (SP6)，Xinshu (BL15), 2 w PSQI, Sleep
201953 malignant 0.4 mg/d moxibustion+C Pishu (BL20), Zusanli (ST36), Danshu (BL19) and Qiuxu (GB40). efficiency,
tumor+insomnia QLQ-C30
Xia Q et 23/23 NR 18/28 Tumor+depression fluoxetine 20 mg/d Scalp-acupuncture SA: Dingzhongxian (MS5), Ezhongxian (MS1), Epangxian(MS2~ MS4), 4 w HAMD,
al 201754 Nieqianxian (MS10), Niehouxian (MS11). SDS,
depression
efficiency
Xia WM 37/37 T: 47.6±8.2 T: 10/27 Thyroid cancer+ Routine care Moxibustion MT: Baihui (GV 20). 7d SDS, SAS,
et al C: 46.2±7.5 C: 13/24 insomnia, anxiety PSQI
201955 and depression
Zeng XL 29/28 T: 60.28±10.22 T: 12/17 Tumor+depression Sertraline 50 mg/d Acupuncture AT: Neiguan (PC6), Shenmen (TF4), Laogong (PC8), The Stabilizing 4w HAMD,
201556 C: 61.71±11.58 C: 13/15 +moxibustion Four-Shen points and the Four-Shen pointsof Jin's Three-needle Therapy. SDS, QLQ-
C30
MT:
Zhang YT 35/34 T: 64.06±9.155 T: 18/17 Tumor+insomnia Routine Thermal MT: Shenque (CV8), Xinshu (BL15), Pishu (BL20), Shenmen (TF4) and 7d PSQI
201757 C: 64.46±10.947 C: 14/20 care+Estazolam moxibustion+C Sanyinjiao (SP6).
1 mg/d (if needed)
Zhang CH 32/32 T: 56.9±5.7 T: 13/19 Tumor+depression Amitriptyline 50- Acupuncture AT: Zusanli (ST36), Sanyinjiao (SP6), Feishu (BL13) and Yinlingquan 6w HAMD,
et al C: 56.8±6.1 C: 14/18 150 mg/d +chinese herb+c (SP9). depression
201758 efficiency
Zhang YL 31/31 18-65 38/24 Colorectal Loperamide 4 mg/d Needle warming Guanyun (CV4), Shenque (CV8), Tianshu (ST25) and Zusanli (ST36). 7d SDS, SAS
et al (53.55±11.60) cancer+anxiety and moxibustion
201759 depression
Zhang B 30/30 T: 59.8±4.3 T: 13/17 Tumor+depression Chinese herb Five-element The acupoints according to five-element acupuncture therapy. 6w HAMD
201760 C: 58.4±5.2 C: 15/15 acupuncture+C
Zhao YL 93/97 T: 59.36±12.541 T: 60/33 Tumor+insomnia Estazolam 1 mg/d Acupuncture+mox AT: Baihui (GV 20), Shenting (GV24), Yintang (EX-HN3), Shenmen 7d Sleep
201561 C: 60.95±11.112 C: 66/31 ibustion (TF4), Zusanli (ST36) and Sanyinjiao (SP6). efficiency,
PSQI
MT: Shenque (CV8) and Guanyun (CV4).
Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456


Zhu JJ et 50/50 T: 63.38±8.34 T: 37/13 Liver Escitalopram Cake-separated MT: Fengfu (GV16), Geshu (BL17) and Danshu (BL19). 6w HAMD,
al 201762 C: 62.78±7.85 C: 38/12 cancer+depression 10 mg/d moxibustion depression
+Chinese herb efficiency
Notes: T: the treatment group; C: the control group; NR: not reported; AT: acupuncture; MT: moxibustion; EA: Electric acupuncture; IN: intradermal needling; SA: scalp-acupuncture; PSQI: the Pittsburgh Sleep
Quality Index; HAMD: the Hamilton Depression Scale; SDS: the Self-rating Depression Scale; SAS: the Self-rating Anxiety Scale; QLQ-C30: Quality of Life measurement Scale.
 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
Figure 2 Risk of bias graph
A: risk of bias item among included studies; B: risk of bias item in each included study.
envelopes, nine studies did not report, while 2 studies
broke randomization and thus were assigned with high
risk. Because it is impossible to blind participants and
personnel from acupuncture and moxibustion to
conventional treatment, 13 studies were assessed to be a
high ROB. Only 1 study was at low ROB for reporting
the blinding of participants and personnel, while the
other 16 studies were at unclear ROB. All of the included
studies reported the complete outcome data, and we
considered them to be at low ROB. 24 studies had
reported the details of adverse reactions or published
protocols with a low ROB, while the other 6 studies did
not report. 20 studies reported the patients’ baseline
characteristics, while the other 10 studies were assessed
to be at unclear ROB for lack of reporting details. The
overall quality of the trials was assessed as having
moderate to high risk of bias.
Effectiveness assessment
3.4.1 Evaluation of efficacy in insomnia
3.4.1.1. Primary outcome measure: the effective rate of
insomnia
Seven studies38,49,50,52,56,60,64 showed the equivalent
effects of AMT on the cancer related insomnia effective
449
rate, 391 cases in the treatment group and 399 cases in
the control group, with high heterogeneity between the
studies (P < 0.000 01, I2 = 83%). The Meta-analysis was
detailed in Figure 3A. The Meta-analysis showed no
significant difference between the 2 groups [n = 790, RR
= 1.18, 95% CI (0.93, 1.51), P = 0.18].
The subgroup analysis was explained the high
heterogeneity by different intervention of treatment. The
Meta-analysis showed that 4 studies38,49,52,64 showed
significant difference on the effective rate of insomnia
between AMT and conventional drugs [n = 555, RR =
0.89, 95% CI (0.81, 0.98), P = 0.02] with low
heterogeneity (P = 0.32, I2 = 14%), 3 studies50,56,60
showed significant difference on the effective rate of
insomnia between AMT + CD and conventional drugs [n
= 235, RR = 2.18, 95% CI (1.34, 3.56), P = 0.002] with
middle heterogeneity (P = 0.09, I2 = 59%).
3.4.1.2. Primary outcome measure: the Pittsburgh Sleep
Quality Index (PSQI)
Eleven studies38,41,43,50-52,54,56,58,60,64 reported changes in
PSQI, 490 cases in the treatment group and 493 in the
control group, with high heterogeneity between the
studies (P < 0.000 01, I2 = 95%), so random effects
model was used. The Meta-analysis was detailed in
Figure 3B. The results of Meta-analysis showed that the
450 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
Figure 3 Results of the Meta-analysis of the efficacy of insomnia
A: Meta-analysis forest map of the effective rate of insomnia; B: Meta-analysis forest map of PSQI. AMT: acupuncture and moxibustion therapy;
CD: conventional drugs; PSQI: Sleep Quality Index.
difference in the reductions of the PSQI between the
treatment group and the control group was statistically
significant [n = 984, MD = −1.95, 95% CI (−3.01, −0.90),
P = 0.0003].
A subgroup analysis was conducted to explore whether
heterogeneity could be partially explained by different
intervention of treatment. The Meta-analysis showed that
3 studies43,54,58 showed significant difference on PSQI
between AMT and routine care [n = 223, MD = −3.77,
95% CI (−5.43, −2.12), P < 0.000 01] with high
heterogeneity (P = 0.002, I2 = 84%), 4 studies38,51,52,64
showed no significant difference on PSQI between AMT
and conventional drugs [n = 445, MD = 0.10, 95%CI
(−0.75, 0.94), P = 0.82] with high heterogeneity (P =
0.005, I2 = 77%), 4 studies41,50,56,60 showed significant
difference on PSQI between AMT + CD and
conventional drugs [n = 315, MD = −2.77, 95% CI
(−3.67, −1.87), P < 0.000 01] with high heterogeneity (P
= 0.001, I2 = 81%).
3.4.2 Evaluation of efficacy in depression
3.4.2.1 Primary outcome measure: the effective rate of
depression
Seven studies41,44,46,57,59,61,65 showed the equivalent
effects of AMT on the cancer related depression effective
rate, 244 cases in the treatment group and 243 cases in
the control group, with moderate heterogeneity between
the studies (P = 0.02, I2 = 59%). The Meta-analysis was
detailed in Figure 4A. The Meta-analysis showed
significant difference between the 2 groups [n = 487, RR
= 1.29, 95% CI (1.12, 1.49), P = 0.0004].
The subgroup Meta-analysis showed that 1 studies44
showed significant difference on the effective rate of
depression between AMT and routine care [n = 60, RR =
3.00, 95% CI (1.71, 5.25), P = 0.0001], 3 studies57,59,65
showed significant difference on the effective rate of
depression between AMT and conventional drugs [n =
203, RR = 1.18, 95% CI (1.05, 1.32), P = 0.005] with low
 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456 451

heterogeneity (P = 0.50, I2 = 0%), 3 studies41,46,61 showed
significant difference on the effective rate of depression
between AMT + CD and conventional drugs [n = 224,
RR = 1.28, 95% CI (1.09, 1.50), P = 0.003] with low
heterogeneity (P = 0.27, I2 = 24%).
3.4.2.2 Primary outcome measure: HAMD
Twelve studies37,39-41,44,46,48,57,59,61,63,65 reported changes
in HAMD, 383 cases in the treatment group and 387 in
the control group, with high heterogeneity between the
studies (P < 0.000 01, I2 = 94%), so standard random
effects model was used. The Meta-analysis was detailed
in Figure 4B. The results of Meta-analysis showed that
the difference in the reductions of the HAMD between 2
groups was statistically significant [n = 770, SMD =
−1.10, 95% CI (−1.77, −0.43), P = 0.001].
The Meta-analysis of the subgroups showed that 1
studies44 showed significant difference on HAMD
between AMT and routine care [n = 60, SMD = −0.54,
95% CI (−1.06, −0.03), P = 0.04], 5 studies39,48,57,59,65
showed no significant difference on HAMD between
AMT and conventional drugs [n = 330, SMD = −0.62,
95% CI (−1.87, 0.62), P = 0.33] with high heterogeneity
(P < 0.000 01, I2 = 96%), 6 studies37,40,41,46,61,63 showed
significant difference on HAMD between AMT+CD and
conventional drugs [n = 380, SMD = −1.59, 95% CI
(−2.47, −071), P = 0.0004] with high heterogeneity (P <
0.000 01, I2 = 93%).

Figure 4 Results of the Meta-analysis of the efficacy of depression

A: Meta-analysis forest map of the effective rate of depression; B: Meta-analysis forest map of HAMD. AMT: acupuncture and moxibustion
therapy; CD: conventional drugs; HAMD: Hamilton Depression Scale.
452 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456

3.4.2.3 Primary outcome measure: SDS showed no difference on SAS between AMT and
conventional drugs [n = 209, MD = −7.12, 95%CI
13 studies reported changes in
36,41,42,45,47,48,50,53,55,57-59,62
(−14.61, −0.37), P = 0.06] with high heterogeneity (P <
SDS, 519 cases in the treatment group and 525 in the
0.000 01, I2 = 95%), 2 studies42,50 showed significant
control group, with high heterogeneity between the
difference on SAS between AMT+CD and conventional
studies (P < 0.000 01, I2 = 92%), so random effects
drugs [n = 240, MD = −6.60, 95% CI (−11.32, −1.88), P
model was used. The Meta-analysis was detailed in Table
= 0.006] with high heterogeneity (P = 0.07, I2 = 71%).
2 and supplementary Figure 1A. The results of Meta-
analysis showed that the difference in the reductions of
3.4.4 Quality of life (QOL) and adverse events
the SDS between 2 groups was statistically significant
[n = 1044, MD = −9.40, 95% CI (−12.21, −6.59), P < 3.4.4.1 Secondary outcomes: QOL
0.000 01].
Five studies36,37,42,53,56 reported changes in quality of life,
The Meta-analysis of the subgroups showed that 5
162 cases in the treatment group and 161 cases in the
studies36,47,53,55,58 showed significant difference on SDS
control group, with moderate heterogeneity between the
between AMT and routine care [n = 412, MD = −13.28,
studies (P = 0.15, I2 = 40%), so random effects model
95%CI (−17.92, −8.64), P < 0.000 01] with high
was used. The Meta-analysis was detailed in Table 2 and
heterogeneity (P < 0.000 01, I2 = 93%), 5
supplementary Figure 2. The results of Meta-analysis
studies45,48,57,59,62 showed difference on SDS between
showed that the difference in the growth of the QOL
AMT and conventional drugs [n = 312, MD = −6.66,
between 2 groups was statistically significant [n = 323,
95%CI (−12.66, −0.65), P = 0.03] with high
MD = 1.11, 95% CI (0.80, 1.42), P < 0.000 01].
heterogeneity (P < 0.000 01, I2 = 95%), 3 studies41,42,50
The Meta-analysis of the subgroups showed that 2
showed significant difference on SDS between AMT +
studies42,56 showed significant difference on QOL
CD and conventional drugs [n = 320, MD = −7.44, 95%
between AMT and conventional drugs [n = 137, MD =
CI (−9.26, −5.63), P < 0.000 01] with low heterogeneity
1.36, 95%CI (0.99, 1.74), P < 0.000 01] with high
(P = 0.91, I2 = 0%).
heterogeneity (P = 0.31, I2 = 1%), 3 studies36,37,53 showed
3.4.3 Evaluation of efficacy in anxiety significant difference on QOL between AMT+CD and
conventional drugs [n = 186, MD = 0.93, 95% CI (0.59,
3.4.3.1 Primary outcome measure: SAS
1.28), P < 0.000 01] with high heterogeneity (P = 0.28,
Ten studies36,42,45,47,48,50,53,55,58,62 reported changes in SAS, I2 = 22%).
427 cases in the treatment group and 434 cases in the
3.4.4.2 Secondary outcomes: adverse reactions
control group, with high heterogeneity between the
studies (P < 0.000 01, I2 = 88%), so random effects Ten studies38,44,46,48,51,53,54,57,59,62 investigated adverse
model was used. The Meta-analysis was detailed in Table events, whereas other 20 studies did not report. One
2 and supplementary Figure 1B. The results of Meta- studie46 reported a total of 16 mild adverse events in 80
analysis showed that the difference in the reductions of cases including mild skin bruising (n = 8), dizziness (n
the SAS between 2 groups was statistically significant [n = 5), and headache (n = 3) which were improved after
= 861, MD = −7.75, 95% CI (−10.44, −5.05), P < symptomatic treatment. One studie51 investigated that
0.000 01]. adverse events of acupuncture included vertigo, reduced
The Meta-analysis of the subgroups showed that 5 ability of behave while adverse events of taking sleeping
studies36,47,53,55,58 showed significant difference on SAS pills “Estazolam” included hangover, nausea or dizziness,
between AMT and routine care [n = 412, MD = −8.61, and insomnia rebound. Two studies38,48 reported a total of
95% CI (−12.38, −4.84), P < 0.000 01] with high 5 adverse events including pain (n = 1), hematoma (n =
heterogeneity (P < 0.000 01, I2 = 88%), 3 studies45,48,62 2), palpitation (n = 1) and dizziness (n = 1) in the
Table 2 Summary of the Meta-analysis
Trials Participants Mean difference
Risk factor Heterogeneity P value
(n) (n) (95% CI)
SDS 13 1044 −9.40 (−12.21,−6.59) < 0.000 01 < 0.000 01
AMT and routine care 5 412 −13.28 (−17.92,−8.64) < 0.000 01 < 0.000 01
AMT and conventional drugs 5 312 −6.66 (−12.66,−0.65) < 0.000 01 0.03
AMT+CD and conventional 3 320 −7.44 (−9.26, −5.63) 0.91 < 0.000 01
SAS 10 861 −7.75 (−10.44, −5.05) < 0.000 01 < 0.000 01
AMT and routine care 5 412 −8.61 (−12.38, −4.84) < 0.000 01 < 0.000 01
AMT and conventional drugs 3 209 −7.12 (−14.61, −0.37) < 0.000 01 0.06
AMT+CD and conventional 2 240 −6.60 (−11.32, −1.88) 0.07 0.006
QOL 5 323 1.11 (0.80, 1.42) 0.15 < 0.000 01
AMT and conventional drugs 2 137 1.36 (0.99, 1.74) 0.31 < 0.000 01
AMT+CD and conventional 3 186 0.93 (0.59, 1.28) 0.28 < 0.000 01
Notes: CI: confidence interval; SDS: self-rating depression scale; SAS: self-rating anxiety scale; QOL: quality of life; AMT: acupuncture and
moxibustion therapy; CD: conventional drugs.
 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
treatment group; 16 patients’ adverse reactions including
fatigue (n = 1), dizziness (n = 3), nausea (n = 4),
sweating (n = 2), and dry mouth (n = 5) in the control
group. Two studies48,51 reported the incidence of adverse
reactions in the treatment group was lower than that in
the control group with significant difference. Five
studies44,53,57,59,62 reported that no significant adverse
reactions were found in either group.
Publication bias
Based on the primary outcome measure including PQSI,
HAMD, SDS and SAS in RevMan 5.3 software, we used
a funnel plot to have a qualitative analysis of publication
bias. The distribution of graphical cues was not
symmetric, and a few points were distributed beyond the
funnel, indicating that there might be publication bias in
our study that influenced the results of our analysis, as
shown in supplementary Figure 3.
Sensitivity analyses
We found that the results of heterogeneity comparing the
PSQI, the effective rate of insomnia, HAMD, SDS, SAS
scale on AMT VS conventional drugs or routine care
were not significantly reduced by omitting the study
sequentially.
However, the results of heterogeneity comparing the
effective rate of depression significantly reduced from
[RR = 1.29, 95% CI (1.12, 1.49), P = 0.0004, I2 = 59%]
to [RR = 1.21, 95% CI (1.11, 1.32), P < 0.0001, I2 = 0%]
after excluding the Liu’s study.41 Therefore, the Liu’s
study41 was regarded as the source of heterogeneity, it
offered inferior evidence for the effect of AMT on
cancer-related depression.
4. DISCUSSION
Acupuncture and moxibustion Intervention
Mechanism
As a new and promising field of research, acupuncture
and moxibustion therapy is strongly needed by more
and more cancer patients and survivors for various
cancer-associated symptoms.63-65 The most common
integrative medicine therapies mentioned on the 45
National Cancer Institute (NCI)-designated
comprehensive cancer center were exercise (97.8%) and
acupuncture and meditation (88.9%).66 A number of
cancer centers in the U.S., including Dana-Farber Cancer
Institute (DFCI) in Boston, Memorial Sloan Kettering
Cancer Center in New York, and M.D. Anderson Cancer
Center in Houston are integrating acupuncture into
cancer care.
The mechanism of AMT on cancer-related psychological
problems has been studied as a new and promising field
of research. The co-occurrence of multiple psycho-
neurological symptoms, including pain, sleep
disturbance, fatigue, depression, anxiety, and cognitive
disturbance among adult cancer survivors, may be
453
associated with hypothalamic-pituitary-adrenal (HPA),
sympathetic nervous system (SNS) dysregulation,67 the
kynurenine metabolic pathway activation,68 the
adenosinergic system,69 and neuroendocrine-immune
mechanisms.70,71 Laboratory studies have provided
evidence for acupuncture’s effect on sleep, depression,
anxiety and psychological distress in cancer survivals by
stimulating the HPA axis,72 SNS system,73 circadian
rhythms, cytokines and neurotransmitters(such as IL-1,
IL-6, neuropeptide Y, serotonin, melatonin, dopamine,
norepinephrine, gamma-aminobutyric acid, β-
endorphins),74-76 which plays a significant role in all
important targets in the psychiatric treatment of
depression and anxiety.77,78 At present, more studies are
needed on the definite mechanism of acupuncture and
moxibustion in patients with CRPS.
Summary of main results
The aim of this study is to evaluate the effectiveness and
safety of AMT in cancer patients with CRPS. After
literature screening, we pooled the data from 30 studies
involving 2483 patients for further analysis. Our pooled
analysis indicates that compared with routine care or
combined with conventional drugs, AMT seems to
improve cancer-related psychological symptoms to a
certain extent, especially in insomnia, depression and
anxiety; besides, it is likely to significantly reduce PSQI,
HAMD, SDS, SAS and increase insomnia effective rate,
depression effective rate and QOL with mild adverse
reactions. In addition, there is no statistically difference
in the therapeutic effects between the AMT and
conventional drug groups. Therefore, compared with
conventional drugs, AMT has the same effects as
antidepressants and anti-anxiety medication to some
extent in improving cancer-related depression and
anxiety.
Another systematic review also suggested that
acupuncture was slightly more effective than
benzodiazepines of anti-insomnia drug, with effective
rate for acupuncture and benzodiazepines being 91% and
75% respectively, and equally as effective as zolpidem
for improving sleep.79, 80 Adverse reactions of AMT have
been observed as being relatively mild, mainly including
bruises, soreness, nausea, and dizziness which can be
effectively avoided by strengthening the aseptic
operation specification, and improving the professional
ability of doctors. Therefore, acupuncture and
moxibustion treatment for CRPS is considered as being
safe and effective, which is worthy of clinical application.
Quality of evidence
Based on the selected criteria, 30 studies involving a total
of 2483 cancer survivors have been included in this study
to illustrate the effect of acupuncture and moxibustion on
the improvement of CRPS. The quality of evidence
differs from low to high based on the Cochrane Bias
Evaluation Tools and Jadad scale. Among the 30 studies
included, 14 studies are of high quality, 3 studies are of
454 Ma FF et al / Journal of Traditional Chinese Medicine 2023 43(3): 441-456
moderate quality, and 13 studies are of low quality.
Therefore, the quality of the included studies is generally
moderate. The inappropriate random method, allocation
concealment, and a lack of blinding in most studies have
exaggerated the results of the outcome measures. In this
study, 76.67% of the literature and 10% of the literature
have correctly reported randomized grouping and
allocation of hidden information, respectively. This
could lead to overestimate.
Discussion of heterogeneity
There was heterogeneity in the effectiveness of AMT on
the total effective rate of psychological symptoms. To
explore its source, we adopted subgroup analysis and
found that clinical heterogeneity could not be explained
for sorts of western medicine and many factors, its
methodological heterogeneity has been mainly affected
by the quality of the included literature and the subjective
bias of literature quality evaluation. Similarly, by
changing the research effect model and adopting the
sensitivity analysis method, we’ve found that the
heterogeneity is significantly reduced after omitting the
study of Liu.41 To explore its reasons, it has been found
that they all have problems such as low quality, the flaw
in test design, or small sample sizes. This indicates that
the results of this Meta-analysis, to a certain extent, have
been affected by the risk of bias.
It seems that AMT is an effective and relatively safe
complementary approach for the treatment of cancer-
related psychological symptoms. However, substantial
heterogeneity was a limitation of the analysis of AMT for
cancer-related insomnia, depression and anxiety. The
variety of intervention and control groups may have
contributed to heterogeneity. But subgroup analysis
(according to the type of intervention, type of the
acupuncture and moxibustion) could not totally explain
the heterogeneity.
Limitations and advantages
There were several limitations of this systematic review
and Meta-analysis:
Firstly, the evaluation criteria are inconsistent for cancer-
related insomnia, depression and anxiety. There are 11
studies using PSQI, and 7 studies using the effective rate of
insomnia with cancer-related insomnia. There are 12
studies using the HAMD, 13 studies using the SDS, 7
studies using the effective rate of depression with cancer-
related depression. Therefore, it might be one of the
sources of heterogeneity. However, due to the limitation of
the number of included literature and the lack of integrated
data, this review doesn’t distinguish these criteria.
Therefore, it is suggested that clinical studies should be
strengthened in future studies, and clinical effectiveness
should be evaluated by the internationally unified
effectiveness evaluation standards. Thus, the results would
have more authenticity and reliability.
Secondly, the methodological quality of most included
studies is relatively low and results in a latent risk of bias,
which to some extent, weakens the credibility and
reliability of the evidence of AMT for cancer-related
psychological symptoms in this systematic review and
Meta-analysis. For example, with few control groups being
placebo controls or false AMT, it is difficult to eliminate
the placebo effect. Although the word “random” appeared
in all the included literature, only 19 studies described the
random method correctly. In most of the included studies,
allocation concealment and blind method are not clear,
which may lead to potential implementation bias and
selectivity bias. Besides, most of the included RCTs were
conducted in China, and only one article was published in
English. And the results of the funnel plot indicates
potential publication bias.
Compared with published systematic review and Meta-
analysis, literature retrieval in this study is more
comprehensive with systematic literature retrieval strategy
and a larger number of literature is included, ensuring more
reliable and scientific evidence in this study. Regardless of
the potential bias and limitations of this review, all of the
included studies show that AMT intervention seems to
have significant effects in improving cancer-related
psychological symptoms. As an effective adjunct
treatment, AMT intervention has turned to a superior
complementary and alternative medicine with a
treatment modality of potential efficacy and few adverse
effects, reducing the economical burden on health care
resources and the community.
In conclusion, in this systematic review and Meta-analysis
of RCTs, the efficacy and safety of acupuncture and
moxibustion in the treatment of cancer-related
psychological symptoms are confirmed. Acupuncture and
moxibustion have the potential to become an effective
therapy than routine care, and superior to conventional
drugs for it was of the same efficacy on cancer-related
insomnia, anxiety and depression but caused less adverse
reactions.
Nevertheless, limited by the quality of existing published
studies, extreme heterogeneity in the analyses remains
unexplained with few high-quality studies included.
Therefore, further properly designed RCTs with well-
designed, rigorous, large sample, and multicenter
prospective are needed before the AMT therapy could be
widely recommended in the treatment of cancer-related
symptoms, so as to reduce the influence of publication bias,
improve the credibility of research and guide clinical
practice better. The long-term efficacy of AMT
intervention on cancer-related psychological symptoms
should also be evaluated.
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