Matsuura Yuto,at al. Japanese Acupuncture and Moxibustion; 2024; Vol.18: 15–26

Original Research

Acupoints used in acupuncture-based randomized controlled trials for
major depressive disorder: A systematic review
MATSUURA Yuto, TANIGUCHI Hiroshi, KOGA Yoshihisa,
YASUNO Fumiko, SAKAI Tomomi
Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medical and Health Sciences

Abstract[Aim] The effectiveness of acupuncture in treating major depressive disorder (MDD) has been reported byrandomized controlled trials (RCT) and systematic reviews/meta analyses. However, no studies have focused on
describing the specific acupoints used. In this systematic review, we aimed to examine the types of acupoints andfrequency of their use in various interventions, and tendency of differences in effects depending on the acupoints
used in RCTs involving acupuncture for treating MDD.
[Data sources] A literature search of the PubMed database was performed. Study selection: RCTs involving
acupuncture for treating MDD indexed until December 31, 2020, were selected. Data extraction: The acupoints
described in the methods were extracted and counted for each treatment method.
[Main results] Acupoints were described in 29 RCTs. A total of 61 acupoints were used in 29 RCTs. The top
10 acupoints used were GV20 25 (86%), EX-HN3 Yin Tang 21 (72%), PC6 16 (55%), HT7 15 (52%), LR3, SP6
14 (48%), LI4 9 (32%), ST36 7 (25%), EX-HN1 Si Shen Cong, and EX-HN54 An Mian 6 (21%). Manual
acupuncture was performed in acupoints throughout the whole body, and electroacupuncture was concentrated
toward the acupoints of the head. There was no positive and negative trend in the results due to the differencein the acupoints used. The variations in acupoints used were 19 fixed and 4 semi-fixed in China, and 5 fixed and2 semi-fixed in other countries/areas. There were significant differences between China and other countries/areasin the proportion of variations in the acupoints used (P = 0.01). There were no significant differences the mean
total number of acupoints between 6.9 (SD 2.7) for China and 7.3 (SD 5.0) for other countries. The mean total
number of treatments and the mean frequency of treatment were significantly higher in China than other countries(P = 0.01).
[Conclusions] This review clarified the acupoint types, frequencies, and differences in effects of their use in RCTs
involving acupuncture for MDD. The choice of acupoints may vary depending on the treatment. Moreover, there
was no clear trend of differences in effects depending on the acupoints used. These results could be used as abasis for developing specific intervention methods in clinical trials for acupuncture and for selecting clinicalacupoints.
Key words: Acupoints, Acupuncture, Major depressive disorder, Randomized controlled trial, Systematic review

I. Introduction
Major depressive disorder (MDD) is a type ofmood disorder in which the main symptom is a
depressed mood. MDD affects up to 3.0% of theworld's population1). The rate of effectiveness of using
antidepressants for the first time for MDD isapproximately 60% to 70%2) . Early treatment failure
increases the risk of recurring of subsequent
depressive episodes3) . Therefore, in order to resolve
the concerns associated with medication-based
therapy, various non-pharmacological therapies havebeen used as supplementary treatments4-6).
As a non-pharmacological treatment option,acupuncture can be expected to have a therapeutic
effect on MDD. A Cochrane Review stated that
acupuncture may lead to moderate and low levels
reduction in the severity of depression whencompared with routine/no treatment and acupuncture
controls, respectively; however, the quality ofevidence from most included studies was low due tomethodological issues, such as the risk of bias7).
Subsequently, a systematic review and meta-

Corresponding author: Matsuura Yuto, Department of Acupuncture and Moxibustion, Tokyo Ariake University of Medicaland Health Sciences,
Received 28 Sep, 2021 Accepted 24 May, 2024

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analysis8) focusing on the relationship between theacupuncture "dose" and clinical outcomes, conductedusing the same methodology as that of the Cochrane
Review, found that the total number and frequency ofacupuncture treatment sessions were associated withimproved outcomes in patients with depression.
Acupuncture has different effects in treating
depression, depending on the type of intervention;
therefore, it is necessary to describe specificinterventions.
The acupoint prescription is an important factor in
deciding the acupuncture treatment method. The
acupuncturist selects the acupoints to be used basedon clinical symptoms, physical findings, andtraditional oriental medical diagnostic methods.
However, in previous studies that evaluated theefficacy of acupuncture in treating MDD, it was
unclear which acupoints were used and to what
extent. Further, although a systematic review that
included a Cochrane Review highlighted the lack ofmethodological data in the available studies, thedescription of the acupoints used was not focusedupon in any studies. Therefore, we aimed to conduct
a review in order to determine the specific acupoints
that were used in randomized controlled trials (RCTs)
conducted on acupuncture for treating MDD.
Information on the types of acupoints and frequencyof their use can help practitioners develop treatment
protocols and select acupoints in clinical settings. As
a preliminary study, we published, in Japanese, areview of RCTs on acupuncture for treating
depression until 2016, which enumerated theacupoints used9). The present study was designed as asystematic review focused on the acupoints used.
Formulating
standard
andeffective
acupointprescriptions for MDD would not only help reduce
variations in acupoint selection in future clinicalstudies but also optimize treatment planning andbenefit acupuncture clinical practice. Therefore, it ismeaningful to conduct a detailed investigation
focusing on the acupoints used. The purpose of thisreview was to update the knowledge on the topic;
review the RCTs on acupuncture for depression; anddetermine the types of acupoints, frequency of theiruse in various interventions, and tendency for
differences in the effect of acupuncture, depending on
the acupoints used.
II. Materials and Methods
1. Search strategies
The literature search was performed on June 14,
2021. We searched for articles indexed in PubMed
until December 31, 2020. The following search terms
were used: ("acupuncture[tiab]" OR "acupuncture[mh]"OR "acupuncture therapy[tiab]" OR "acupuncture

therapy[mh]" OR "electro acupuncture[tiab]" OR"electro acupuncture[mh]") AND ("depression[tiab]"OR"depression[mh]"OR"majordepressive
disorder[tiab]" OR "major depressive disorder[mh]").
A clinical trial filter was set in order to extract only
the articles related to clinical trials. All the searchsteps were performed by one author (YM).
2. Eligibility criteria
The articles that were considered eligible for thisreview were RCTs evaluating the efficacy ofacupuncture in treating MDD. RCTs were excluded ifthey included additional treatments, such astranscutaneous electrical nerve stimulation andacupressure that were not used in combination withacupuncture, even if they involved the use of
acupoint-related interventions. The diagnostic criterion
for the patients in the eligible RCTs was primary
depression only. Therefore, we excluded articles that
dealt with non-diagnosed depression, post-stroke
depression, postpartum depression, bipolar depression,and depression associated with physical disorders.
From the extracted articles, 1) those written inlanguages other than English, 2) those that included acondition that could not be identified as MDD or
included bipolar depression, 3) those that included
postpartum depression or depression associated withphysical disorders, 4) protocol papers, 5) non-RCTs,
6) those that did not involve an acupunctureintervention, and 7) secondary analyses or secondary
publications were excluded.
3. Aggregation of used acupoints
Regarding the acupoints used, those listed inrelation to each intervention method were aggregated.
If adjunctive treatments, such as moxibustion (MOX)
and intradermal acupuncture (IA) (a type acupuncture
method performed by inserting sterile map pin-type
needles into the subcutaneous acupoints on the body,and then burying the needle in the body for a longtime), were combined with acupuncture, the acupoints
used in these treatments were also included in the
count. The inclusion criteria for counting specificacupoints were as follows:
・The code of the acupoint was defined in the World
Health Organization (WHO) standards10)
・Ear acupoints
・ Minimal acupuncture performed at specificacupoints related to MDD (considered as manual
acupuncture [MA])The exclusion criteria for acupoint aggregation wereas follows:・Acupoints reported in the Results section with nodescription provided in the Methods section
・ Acupoints whose location had been intentionally
moved in order to function as sham acupoints

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17・ WHO-coded acupoints that were used as nonspecific acupoints for the treatment of MDD・ Specific acupoints that were stimulated with aplacebo needle
・Acupoints with no description

study used clear inclusion criteria for selecting
acupoints, unlike our previous preliminary study thatused only simple tabulation9）. Furthermore, we also
focused on the acupoints used for each intervention
method to provide useful data for clinical practice.

(1) Aggregation of the used acupoints described in
RCTs
The total number of acupoints used in each RCT
were recorded. The frequency of use of each acupoint
was calculated. When the same acupoints were usedin the comparison of different treatments within asingle RCT, they were not counted twice.

(1) Relationship between the acupoints used andoutcomes
We investigated the relationship between the 10
most frequently used acupoints in the RCTs and therelated outcomes. Acupoints were calculated for RCTs
that were designed as "acupuncture vs. medication" or"acupuncture + medication vs. medication alone". In
the analysis, the RCTs were classified into positive
and negative based on the results, and the usage ratein the acupoints of the top 10 usage frequencies wascalculated.

(2) Aggregation of the acupoints used in different
treatment methods
To determine the acupoints used in each treatment
method, the acupoints in each treatment group were
aggregated if the study design involved comparisonsamong different treatment methods.
4. Data analysis
We summarized the data on the sample sizes, study
design, number of treatments, frequency of treatment,intervention types, variations in acupoints (fixed/semifixed), and acupoints used in the selected papers. This

(2) Frequency of used acupoints on body and head in
MA and EA
The sites of acupoints in this study were defined asfollows: "body" - included the trunk and limbs below
the neck; "head" - started from the face to the lower
edge of the occipital bone. The frequencies ofacupoints used on the body and head in MA andelectroacupuncture (EA) were aggregated.

Figure 1. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart

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Matsuura Yuto,at al. Japanese Acupuncture and Moxibustion; 2024; Vol.18: 15–26

Figure 2. Relationship between manual acupuncture and electroacupuncture groups of top 10 frequently usedacupoints and outcomesMatsuura Yuto,at al. Japanese Acupuncture and Moxibustion; 2024; Vol.18: 15–26

21(3) Comparison of interventions in China and othercountries/areas
Variations in acupoints, total number of acupoints,
total number of treatments, and frequency oftreatment were tabulated to compare the differences inintervention methods between China and othercountries/areas. The total number of acupoints werecounted only when the acupoints used in the paper
were described.

in acupoints in China and other countries/areas werecompared using Fisher's exact test. The total numberof acupoints, total number of treatments, andfrequency of treatment were compared by MannWhitney U test. The statistical analyses were
performed using GraphPad PRISM 6.0 (GraphPad
Software, San Diego, USA). Statistical tests wereconducted using a two-sided significance level of
0.05.

5. Statistics analysis
The frequency of use in MA and EA in body orhead was compared by chi-square test. The variations

III. Results
Figure 1 shows the flow diagram of the search22

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process performed in the present study. A total of 29
studies were included in this review11-43) . Of the 29
studies, 22 were from China, and 7 were from othercountries/areas. Table 1 outlines the characteristics of
the included studies. References 15-39 were cited in
our preliminary study9). References 11-14 are the newstudies included in the present review.
1. Aggregation of used acupoints
Specific acupoints were described in 29 RCTs. Of
these, 23 included fixed interventions, and 7 included
semi-fixed interventions (one duplicate article was
excluded). A total of 61 different acupoints were usedin the 29 RCTs. The following were the top 10
acupoints used: GV20 25 (86%), EX-HN3 Yin Tang
21 (72%), PC6 16 (55%), HT7 15 (52%), LR3, SP6
14 (48%), LI4 9 (32%), ST36 7 (25%), EX-HN54 An
Mian, and EX-HN1 Si Shen Cong 6 (21%) (Table 2).
2. Aggregation of the acupoints used in eachtreatment method
In the 29 RCTs that described the acupoints thatwere used, there were 37 acupuncture groups thatwere divided according to five types of treatment
methods (46 groups by treatment type): MA (n=18),
EA (n=17), IA (n=5), MOX (n=4), and laser
acupuncture (LA) (n=2). Table 3 presents theacupoints used in each intervention method.
A total of 52 acupoints were used in MA. The top

10 acupoints used in MA were GV20, PC6 13 (72%),
LR3 12 (66%), EX-HN3 Yin Tang, HT7 9 (50%),
SP6, LI4 6 (33%), GV15 5 (28%), GB20, GV16, andGV24 4 (22%).
A total of 23 acupoints were used in EA. The top
10 acupoints used in EA were GV20 15 (88%), EXHN3 Yin Tang 14 (82%), PC6 10 (58%), HT7, LR3,
SP6 5 (29%), EX-HN1 Si Shen Cong 4 (24%), EXHN54 An Mian, LI4, and ST36 3 (18%).
A total of five acupoints were used in IA: BL15 5(100%), BL18 (80%), BL19, BL23, and EX-HN54
An Mian 1 (20%).
A total of two different acupoints were used in
MOX: BL17 and BL19 4 (100%).
A total of 10 acupoints were used in the LA:
CV14, HT7, LR8, LR15 4 (100%), CV15, GV20,
KI3, KI10, LI4, and SP6 1 (50%).
3. Relationship between top 10 most frequently usedacupoints and associated outcomes
Figure 2 shows the percentage of positive andnegative RCT results for the top 10 most frequently
used acupoints. GV20: 17 (100%) positive, 10 (91%)
negative; EX-HN3: 15 (88%) positive, 8 (73%)
negative; PC6: 12 (71%) positive, 6 (55%) negative;
HT7: 8 (47%) positive, 7 (64%) negative; LR3: 8(47%) positive, 5 (45%) negative; SP6: 9 (53%)
positive, 6 (55%) negative; LI4: 4 (24%) positive, 3(27%) negative; ST36: 4 (24%) positive, 3 (27%)

Matsuura Yuto,at al. Japanese Acupuncture and Moxibustion; 2024; Vol.18: 15–26

negative; EX-HN1: 2 (12%) positive, 4 (36%)
negative; EX-HN54: 2 (12%) positive, 3 (27%)
negative.
4. Frequency of used acupoints on the body and headin MA and EA
For MA, there were 111 acupoints in the body and
37 in the head; for EA, there were 43 in the bodyand 35 in the head. There were significant differencesin the proportion of used acupoints on the body andhead between MA and EA (P = 0.002) (Table 4).
5. Comparison of interventions in China and othercountries/areas
The variations in acupoints used were 19 fixed and4 semi-fixed in China, and 5 fixed and 2 semi-fixedin other countries/areas. There were significant
differences between China and other countries/areas in
the proportion of variations in the acupoints used (P= 0.01). The mean total number of acupoints was 6.9(SD 2.7) for China and 7.3 (SD 5.0) for othercountries, and there was no significant difference inthe number of acupoints described in the articles fromdifferent countries. The mean total number oftreatments was 26.9 (SD 13.7) for China and 13.9
(SD 5.7) for other countries/areas (P = 0.001). The
mean frequency of treatment was significantly higher
in China at 3.7 (SD 1.4) days a week than that inother countries (2.4 [SD 1.2] days) (P = 0.01) (Table
5).
IV. Discussion
In this review, we aimed to determine theacupoints used for treating MDD, via comprehensive
search of RCTs on acupuncture for treating MDD in
PubMed. In all, 29 papers were included in thisreview. The selected articles were examined, and theacupoints used for treating MDD were clarified.
Furthermore, we aggregated the acupoints used ineach treatment method and demonstrated that the
selected acupoints might differ depending on thetreatment method. Additionally, the association
between frequently used acupoints and outcomes
showed different trends in the MA and EA groups.
There was no clear trend of differences in the effects
depending on the acupoints used. These results
support the rationale for developing specificintervention methods in clinical trials involving
acupuncture and for the selection of clinicalacupoints.
Among the 29 articles that reported the acupoints,
23 reported fixed interventions, and 7 reported semifixed interventions (1 article was a duplicate). A totalof 61 acupoints were used in the RCTs. The RCT by
MacPherson et al40). included 755 patients with MDD;

23

it was conducted in the United Kingdom and was
designed to administer conventional care combinedwith fully individualized acupuncture interventions;further, acupuncture was performed by 23
practitioners, and a total of 246 acupoints were used.
In our review, a total of 61 acupoints were used,which is considerably lesser than the number used in
the RCT by MacPherson et al40). This may be because
specifying fixed acupoints is unavoidable when
standardizing interventions in a study. These data
indicate that the use of acupoints in clinical trials
may be a fairly limited intervention.
On investigating the acupoints used by treatment
method, we found that the points used in MA weredispersed across the whole body, while those used in
EA were concentrated in the head region. Zang etal25). conducted an RCT to examine the effect of an
EA technique called dense cranial electroacupuncture
stimulation (DCEAS) that focused on the head. In
their study, the antidepressant effects of DCEAS were
described as "biophysical and biochemical effects
produced in needling with subsequent electricalstimulation."
Further, GV20 and EX-HN3 Yin Tang are
acupoints that have been empirically used for
depressive symptoms. The main purpose of
performing EA in the head region may be to apply
the theory of neuromodulation to empiricallydetermined acupoints. The acupoints in EA may be
predominantly located on the head because of the useof modern medical MDD treatments that areadministered for neuromodulation, such as repetitivetranscranial magnetic stimulation and electroconvulsive
therapy41) . Interestingly, on investigating therelationship between the results for each acupoint in
the MA and EA groups, we found that EA was notalways superior. Although our results were derived
from simple tabulation, it may serve as a reference
for treatment planning and selection of acupoints. The
results of this study can be the basis for theappropriate use of acupoints in MA and EA inclinical practice.
This study has several limitations. First, this study
did not evaluate the quality of the individual studies
and interventions based on the standards for reportinginterventions in clinical trials of acupuncture(STRICTA)42) ; therefore, the specifics regarding how
different acupoint selections affected outcomes could
not be reported. Second, only the PubMed database
was used for the literature search; therefore, articles
written in languages other than English were notexamined. If articles from multiple databases, such as
Embase and Cochrane Controlled Register of Trials,
and those written in languages other than English
were extracted, our review would have been morecomprehensive. Considering that there are several

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Matsuura Yuto,at al. Japanese Acupuncture and Moxibustion; 2024; Vol.18: 15–26

reports from China, multilingual papers may havepresented more comprehensive data.
Additionally, a manual search of references inindividual papers was not performed and contact withindividual researchers or experts was not attempted.
Therefore, unpublished papers were not included inthis review. Third, there was a lack of information
regarding the technical specifics of electroacupuncture,such as the frequency (Hz) utilized, and the technicalparameters for laser acupuncture, such as wavelength,
output power, power density, energy density, dose
range, and whether the laser used was continuous orpulsed. The differences in these parameters correlatedwith the dose-effect and were related to themagnitude of the biological response43) . Fourth, ourfindings showed that the total number and frequencyof treatments differ between China and other regions.
Therefore, regional differences should also be
considered. The results of this study must be
interpreted keeping in mind the limitations.
V. Conclusion
This study revealed the findings of RCTs on theuse of acupuncture for treating MDD, with a focus on
the acupoints used. There was no tendency for
differences in the effects depending on the acupoints.
The results of this study can be useful as basic datafor developing intervention protocols in future clinical
trials and for selecting acupoints during treatment.
Acknowledgment
We would like to thank Editage (www.editage.com)
for English language editing.
Author contributions
YM
contributed
toconceptualization.
YM
contributed data collection and drafted the originaldraft of the manuscript. YM and HT contributed toformal data analysis and interpretation and assisted in
the preparation of the manuscript. YK, FY, and TS
critically reviewed and edited the manuscript. All
authors approved the final version of the manuscript
and agree to be accountable for all aspects of thework and ensuring that questions related to theaccuracy or integrity of any part of the work areappropriately investigated and resolved.
Conflict of interests
There is no conflict of interest.
Funding
This work was supported by a specific research
grant from Tokyo Ariake University to TS.

Ethical statement
No ethical approval
manuscript.

wasrequired

for

this

Data availability
Data will be made available on request.
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