Sleep Medicine 93 (2022) 39e48

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Sleep Medicine
journal homepage: www.elsevier.com/locate/sleep

Review Article

Comparative effectiveness of multiple acupuncture therapies for

primary insomnia: a systematic review and network meta-analysis of
randomized trial
Yao Lu a, b, Hongfei Zhu a, b, 1, Qi Wang a, b, Chen Tian a, b, Honghao Lai a, b, Liangying Hou c,
Yafei Liu a, b, Ya Gao c, d, Ming Liu c, Fengwen Yang e, Xiaojia Ni f, g, Liyu Lin h,
Junqiang Niu i, ***, Jinhui Tian c, j, **, Long Ge a, b, j, *
a
Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China
b
Evidence-Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
c
Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
d
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
e
Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China
f
Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical School of Chinese Medicine, Guangzhou, China
g
Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
h
Psychology and Sleep Department of Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
i
Department of Traditional Chinese Medicine, The First Hospital of Lanzhou University, Lanzhou, China
j
Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China

a r t i c l e i n f o a b s t r a c t

Article history: Background: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative
Received 30 January 2022 benefit and harm among acupuncture therapies remain uncertain.
Received in revised form Objectives: To compare and evaluate the effect differences of multiple acupuncture therapies for patients
13 March 2022
with PI.
Accepted 15 March 2022
Available online 24 March 2022
Methods: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers inde-
pendently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was
conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and
Keywords:
Primary insomnia
Evaluation system (GRADE) was used to assess certainty of evidence and interpret results.
Meta-analysis Results: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple
Acupuncture therapy acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints
catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence;
auricular acupressure or auricular acupuncture plus manual acupuncture (AP þ MA), electroacupuncture
plus acupoint application (EA þ APA), and intradermal needle (IN) might be also the most effective with
low certainty of evidence. ACE, ACE þ MA, AP þ MA, EA, EA þ APA, HPN, MA and PBN þ MA showed
significantly improvement in effective rate when compared with usual treatment. Insufficient evidence
reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common
slight adverse events mainly included hematoma, pain, headache, and bleeding.
Conclusions: With moderate to low certainty of evidence, multiple acupuncture therapies showed
impressive insomnia improvement, especially ACE, AP þ MA, and EA þ APA. Differences between
therapies were small or insignificant and based-on low or very low certainty of evidence.
© 2022 Elsevier B.V. All rights reserved.

Abbreviations: FN, fire needle; MA, acupuncture; BA, balance acupuncture; EA, electroacupuncture; AP, auricular acupressure or auricular acupuncture; ACE, acupoints
catgut embedding; APA, acupoint application; PBN, plum blossom needle; HPN, head penetration needling; IN, intradermal needle; Usual, usual treatment; SA, sham
acupuncture.
* Corresponding author. Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
** Corresponding author. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
*** Corresponding author. Department of Traditional Chinese Medicine, The First Hospital of Lanzhou University, Lanzhou, China.
E-mail addresses: niujunqiang2020@126.com (J. Niu), tjh996@163.com (J. Tian), gelong2009@163.com (L. Ge).
1
Joint first authors.

https://doi.org/10.1016/j.sleep.2022.03.012
1389-9457/© 2022 Elsevier B.V. All rights reserved.
Y. Lu, H. Zhu, Q. Wang et al.
1. Introduction
Insomnia is a common sleep disorder and one of the most
common health problems in the population and clinical practice
that 30%e50% of the general population has suffered from
Refs. [1,2]. Primary insomnia (PI), the most frequent diagnosis, is
defined as the subjective difficulty in initiating or maintaining sleep
or non-restorative sleep that lasts for at least one month by The
fourth edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-IV), prevalence ranging from 2% to 4% [3]. Insomnia
is associated with higher rates of hypertension, depression, and
affects the quality of life, the risk of traffic accidents and daily work
performance [4e8]. Therefore, insomnia treatment is essential
from the negative effects from insomnia perspectives. The thera-
pies of insomnia include mainly pharmaceutical and non-
pharmacological treatments, and pharmaceutical treatments of
suitable efficacy are widely used for insomnia symptoms [9].
However, the attention of nonpharmacological treatments is
increasing when people worry about the safety of pharmaceutical
treatments [2,10].
Acupuncture has been used to treat many diseases including
primary insomnia [3,11e16]. Acupuncture made of metal and
pointed body into one or some fixed acupoints of the human body.
According to traditional Chinese medicine, acupuncture is consid-
ered that stimulation at specific body regions (acupoints) can
modulate body physiology at distant sites to treat diseases [17].
Acupuncture includes various types, such as manual acupuncture,
electro-acupuncture, fire-needle.
The effectiveness of some acupuncture techniques in treating
insomnia symptoms has been confirmed in some systematic re-
views and overviews [18e25]. Chinese Acupuncture Association
guideline published in 2014 recommended multiple acupuncture
therapies, however, it was mainly based-on systematic reviews and
meta-analyses of observational cohort studies. As alternative
treatment options increase, comparative effectiveness research has
been necessary [26,27]. Which intervention works best? To date,
none of systematic reviews have comprehensively compared and
evaluated the efficacy and safety of multiple types of acupuncture
therapy. The differences between acupuncture therapies remain
unclear. Systematic reviews have mainly relied on pairwise com-
parisons, lacking of results compared with multiple interventions of
effectiveness or safety. For insomnia patients or decision-makers,
they are still not known which acupuncture technique is the best
choice for treating insomnia. Network meta-analysis(NMA) has
been proposed to be the highest level of evidence in the treatment
guideline [28]. Different from a conventional pairwise analysis,
NMA analyzes simultaneously both the direct and the indirect ev-
idence from different studies, estimation of the relative effective-
ness among all interventions, and rank ordering of the
interventions [29,30]. The method is helpful to summarize evidence
across many interventions and make optimal clinical decision [31].
Meanwhile, to avoid making spurious judgments of the evidence,
Grading of Recommendations, Assessment, Development, and
Evaluation (GRADE) approach has been used widely as a response
for the certainty of the evidence [32]. Therefore, the purpose of this
study was to comprehensively compare and evaluate the efficacy
and safety of different acupuncture therapies for insomnia by
integrating all available evidence.
2. Methods
2.1. Eligibility criteria
We included RCTs focused on patients with primary insomnia
that compared acupuncture therapies for treatment against one
40
Sleep Medicine 93 (2022) 39e48
another or against usual treatment, sham acupuncture. The
identification of patients with primary insomnia was based on a
recognized criteria such as DSM-IV. No restrictions were applied
based on group form, we included trials of different forms of
acupuncture-related treatments. The types of intervention
including fire needle, manual acupuncture, balance acupuncture,
electroacupuncture, auricular acupressure or auricular acupunc-
ture, acupoints catgut embedding, acupoint application, plum
blossom needle, head penetration needling, intradermal needle,
or a combination of multiple acupuncture therapies, etc. The in-
clusion for control group included sham acupuncture or usual
treatment (usual treatment, no treatment or placebo); or any
acupuncture mentioned above. Based-on 2014 CAA Guideline, the
outcomes we concentrate on included Pittsburgh sleep quality
index (PSQI) [33], Athens insomnia scale (AIS) [34], Epworth
sleepiness scale (ESS) [35], traditional Chinese medicine syn-
drome score (TCM Syndrome score), effective rate, adverse effects,
and recurrence rate.
We excluded studies that intervention or control was western
medicine or combined with western medicine, only reported
overall improvement rate, or collected patients retrospectively and
then group patients randomly.
2.2. Information sources
We conducted comprehensive searches through to May 2020
from 8 databases, including PubMed, EMBASE, Cochrane Central,
Web of science (WOS), China National Knowledge Infrastructure
(CNKI), China Science and Technology Journal Database (VIP),
WANFANG, and Sinomed. A supplementary search was conducted
in March 14 2021. Reviewers browsed and tracked the reference
entries of trials and related systematic reviews to identify poten-
tially eligible studies. No restriction was applied on the date, lan-
guage, or publication status. The detailed search strategies can be
found in Appendix Text A.1.
2.3. Study selection
To determine comparisons that are applicable, we used a
rigorous eligibility criterion. Two reviewers independently
browsed and selected eligible studies through titles and abstracts,
using Rayyan [36]. Further, they evaluated the full text to identify
potentially eligible studies. Any conflict and disagreement had been
resolved by a third reviewer with discussion and consultation.
2.4. Data collection
Two reviewers, using standardized form and Microsoft Excel
spreadsheets, independently extracted data of each eligible RCT.
Any adjustments and judgments had been resolved by a third
reviewer. Reviewer collected trials information including study
characteristics (year of publication, country, funding), patients
characteristics (sample size, age, sex, disease duration, marital
status, and education status), description of intervention and
control groups (the name, acupoints, acupoints modifications,
operation, treatment duration, duration of follow-up, and fre-
quency), diagnostic criteria and outcomes (PSQI, ESS, AIS, TCM
Syndrome score, effective rate, adverse effects and recurrence
rate).
2.5. Assessment of risk of bias
Two reviewers independently evaluated risk of bias using 2011
Cochrane Handbook tool, which includes random sequence gen-
eration, allocation concealment, blinding of participants and
Y. Lu, H. Zhu, Q. Wang et al.
personnel, blinding of outcome assessors, incomplete outcome
data, selective outcome reporting, and other sources of bias [37].
We answered each domain as low risk of bias criteria, unclear
criteria, and high risk of bias. Any disagreements were resolved by a
third reviewer.
2.6. Data synthesis
When studies reported data as measures before and after
intervention, we used methods outlined in the Cochrane Handbook
5.1.0 to calculate mean change and standard deviations for change
[37]. Appendix Text A.2 presents more details about methods for
imputation of missing standard deviations. We conducted pairwise
meta-analysis using bayesian random effects models to obtain the
pooled direct estimates and forest plots of the available direct
comparisons [38]. Heterogeneity among individual studies was
assessed with the forest plots and quantified with the I2 statistic
[38,39] (details see Appendix Text A.3).
We performed a bayesian random effect network meta-analysis
to compare relative effectiveness of different types of acupuncture
therapies [40e42]. We used three Markov-chain Monte-Carlo
chains with 100,000 iterations after an initial burn-in of 10,000 and
a thinning of 1. We assessed the convergence based on trace plots
and the BrookseGelmaneRubin statistic, with an acceptable
threshold of <1.05. We used non-informative priors for all param-
eters and assumed a common heterogeneity parameter for all
treatment comparisons. Dichotomous outcomes calculated by risk
ratios (RR) and corresponding 95% credible intervals (95% CI). For
continuous outcomes, we used the mean difference (MD) and
corresponding 95% CI. We checked the inconsistency (incoherence)
using the node-splitting method to obtain contrasting estimates
from both direct and indirect evidence [43]. We also calculated the
ranking probabilities of being the best, second best, and so on for all
treatment options and analyzed the surface under the cumulative
ranking curve to rank the intervention hierarchy in the network
meta-analysis [44].
Statistical analyses were performed using the gemtc package of
R version 4.0.3 (R Core Team, Vienna, Austria) and JAGS version
4.3.0 (Just Another Gibbs Sampler). Networkplot command of Stata
version 15.1 (Stata Corp, College Station, Texas, USA) was used to
draw the network plots that consist of nodes representing the in-
terventions being compared and edges representing the available
direct comparisons [45].
2.7. Assessment of the certainty of evidence
We assessed the certainty of evidence using the GRADE
approach. For direct comparisons, we assessed the risk of bias,
indirectness, imprecision, inconsistency, and publication bias
[32,46e52]. For indirect comparisons, the lowest ratings of the two
direct comparisons forming the most dominant first-order loop (for
example, compared A with C is based on comparisons of A and B as
well as C and B) were considered. If there is no first-order loop, we
considered higher order loops (more than two direct comparisons)
to rate certainty of evidence and used the lowest ratings of the
multiple direct comparisons.
The higher rating of the direct or indirect estimates was applied
to the certainty of evidence for NMA and categorized as high,
moderate, low, or very low. Then, we will consider to rate down the
certainty of evidence in the network estimate if we found inco-
herence between direct evidence and indirect evidence under the
same measure. The starting point for the certainty of RCTs is high,
but presented ultimately quality of evidence as high, moderate,
low, very low by evaluation principles [32]. Appendix Text A.3
presents additional details of the GRADE assessment.
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Sleep Medicine 93 (2022) 39e48
2.8. Summary of more and less preferred treatments
In order to make a better presentation for the results of network
meta-analysis for PSQI outcome, we established different groups of
interventions of outcome (from the most to the least effective) on
account of the effect estimates of the meta-analysis and their cer-
tainty of evidence [53].
Firstly, we defined “usual treatment” as the reference, and
dividing into two groups. Group zero refer to as “among the least
effective”, which the reference “usual treatment”, sham acupunc-
ture or acupuncture interventions that did not differ from the
reference (that is, confidence interval crossed mean difference ¼ 0).
Secondly, acupuncture interventions superior to the reference, but
not superior to any other acupuncture superior to the reference
(which we call category 2 and describe as “inferior to the most
effective, but superior to the least effective”), called Group two.
Lastly, acupuncture that proved superior to at least one category 2
(which we call “among the most effective”), called Group one. We
then divided all three categories into other two groups: those with
moderate or high certainty evidence relative to the usual treatment,
and those with low or very low certainty evidence relative to the
usual treatment [54].
3. Results
Of 8326 potentially relevant references identified (7792 from
each database and 534 from supplement searches), 217 were
moved to full-text screening after title and abstract screening.
Finally, we included 57 RCTs for our review (see Fig. 1). Appendix
Text A.4 presents the list of eligible studies.
3.1. Study characteristics
Appendix Tables A.2eA.3 summarizes the characteristics of
included 57 RCTs, with sample sizes from 27 to 340, involving 4678
participants, with a mean proportion of male of 36.32, a range of
mean age of 31.00-70.00 years.
Fifty-seven RCTs included 14 acupuncture therapies (FN, fire
needle; MA, acupuncture; BA, balance acupuncture; EA, electro-
acupuncture; AP, auricular acupressure or auricular acupuncture;
ACE, acupoints catgut embedding; APA, acupoint application; PBN,
plum blossom needle; HPN, head penetration needling; IN, intra-
dermal needle) and 2 control treatments (usual treatment, sham
acupuncture). Fig. 2 presents the network graph of all included
studies. The most common comparison was between MA and sham
acupuncture, followed by MA and usual treatment.
3.2. Risk of bias
The summary of risk of bias is provided in Appendix
Table A.5eA.6. Eleven articles were judged to be unclear risk of
bias in random sequence generation. Thirty-one articles were un-
clear risk of bias in adequate allocation concealment. Thirty articles
were unclear risk of bias and five were high risk of bias in blinded
outcome assessment. In terms of incomplete outcome data, three
studies were judged as to be high risk of bias. Three studies showed
high risk of selective reporting, and one study showed high risk of
other bias.
3.3. Network meta-analysis
Appendix Figs. A.1eA.7 shows network plots for each outcome.
Appendix Tables A.7 and A.9 present GRADE assessments for effec-
tive rate and TCM syndrome score with the number of included RCTs,
sample size, I2, direct estimates, indirect estimates, intransitivity, and
Y. Lu, H. Zhu, Q. Wang et al.
Fig. 1. Flow diagram of literature selection.
incoherence assessment. No evidence network incoherence was
found (Appendix Figs. A.12eA.13). Much of the evidence was judged
as low certainty, rated down most often because of serious risk of
bias and imprecision. Appendix Fig. A.14 shows the surface under the
cumulative ranking curve for each outcome.
3.3.1. PSQI
Forty-five RCTs reported on PSQI, involving 3156 participants
and 14 acupuncture therapies. Compared with usual treatment,
most types of acupuncture therapy showed a better effect for PSQI
score (see Fig. 3). There were no significant differences for most of
comparisons between acupuncture therapies (see Fig. 3). Among
the acupuncture therapies with high or moderate certainty evi-
dence relative to usual treatment, ACE proved the most effective
acupuncture therapy, whereas FN, HPN, ACE þ MA, PBN þ MA,
ACE þ AP, and MA were inferior to the most effective but superior to
42
Sleep Medicine 93 (2022) 39e48
the least effective acupuncture therapies. Among the acupuncture
therapies with only low or very low certainty evidence relative to
usual treatment, AP þ MA, EA þ APA, IN might be the most effec-
tive, whereas AP, EA and PBN were might inferior to the most
effective but superior to the least effective acupuncture therapies.
BA and sham acupuncture were might the least effective in-
terventions (see Fig. 4).
3.3.2. Effective rate
Thirty-nine RCTs were included, involving a total of 2649 pa-
tients. Moderate certainty of evidence presented that ACE,
ACE þ MA, MA, AP þ MA, HPN, and PBN þ MA could significantly
improve the effective rate when compared with usual treatment.
Low certainty of evidence showed that EA and EA þ APA were
better than usual treatment. No significant differences were found
among different acupuncture therapies (see Fig. 3).
Y. Lu, H. Zhu, Q. Wang et al. Sleep Medicine 93 (2022) 39e48

Fig. 2. Network plot of all included studies.

Fig. 3. Network meta-analysis results with corresponding GRADE certainty of evidence for PSQI and overall effective rate. Values correspond to difference in PSQI reduction
(fraction, above right) and overall effective rate (below left) between column and row (e g, ACE had a PSQI reduction of 6.21 and growth in efficiency of 2.54 compared with Usual).
Values in bold indicate a statistically significant treatment effect. The dark gray refers to there is no relevant comparison.

43
Y. Lu, H. Zhu, Q. Wang et al.
Fig. 4. Summary of results of all intervention network meta-analysis for PSQI. The number is the point estimates of effect in comparison with Usual.
3.3.3. TCM syndrome score
Data on TCM syndrome score were available from thirteen RCTs,
involving 826 participants and 7 acupuncture therapies. Compared
with usual treatment, AP þ MA and ACE þ MA could improve the
TCM syndrome score (MD ¼ 6.57, 95% CI: 0.19, 13.17, moderate
certainty; MD ¼ 5.87, 95% CI: 0.69, 11.34, moderate certainty;
respectively) (see Fig. 5).
There is a comparison group not in the network, the result
presented EA þ APA is better than EA, but the evidence was low
(Appendix Table A.10).
3.3.4. ESS
ESS was reported in 3 RCTs, involving 196 participants and 3
acupuncture therapies. Compared with MA, AP þ MA (MD ¼ 2.99,
95% CI: 1.18, 4.80; low certainty) and FN (MD ¼ 1.20, CI: 0.07, 2.33;
low certainty) showed significantly better benefit (Appendix
Table A.11).
44
Sleep Medicine 93 (2022) 39e48
3.3.5. AIS
AIS was reported in 4 RCTs, involving 406 participants and 1
acupuncture therapies. Compared with usual treatment, MA was
significantly more effective (MD ¼ 3.56, 95% CI: 0.81, 6.31; low
certainty) (Appendix Table A.12).
3.3.6. Recurrence rate
Five RCTs reported recurrence rate, involving 409 participants
and 6 acupuncture therapies. Compared with AP, ACE þ AP could
reduce the recurrence rate (RR ¼ 0.23, 95% CI: 0.07, 0.80; low cer-
tainty). No significant differences were found among other com-
parisons (Appendix Table A.13).
3.3.7. Adverse events
We did not perform meta-analysis for adverse events because of
sparse data and heterogeneity. Twenty-two RCTs enrolling 3382
participants reported on adverse events. We summarized the
Y. Lu, H. Zhu, Q. Wang et al. Sleep Medicine 93 (2022) 39e48

Fig. 5. Network meta-analysis results with corresponding GRADE certainty of evidence for TCM syndrome score. Values correspond to difference in TCM syndrome score reduction
between column and row, for positive values the acupuncture indicated in the column is favored (e g, ACEþMA had a reduction of 5.87 fraction compared with Usual). Values in bold
indicate a statistically significant treatment effect.

incidence of adverse events in Table 1. The most common adverse
events from acupuncture interventions included hematoma, pain,
headache, and bleeding.
4. Discussion
4.1. Main findings
As of now, for primary insomnia, this study is the first network
meta-analysis using GRADE approach. In this network meta-
analysis, we pooled evidence from 57 studies with 4678 patients.
In the improvement of PSQI score and effective rate, ACE,
AP þ acupuncture, and EA þ APA were better than other therapies.
Previous study has also confirmed ACE was better than usual
treatment and manual acupuncture in PSQI score reduction and
effectiveness [55e57]. The reason for the better effect of ACE may
be the continuous stimulation of the body using catgut segments
[58,59]. Combining AP with MA is also a good option. The effec-
tiveness of AP is the same as the previous meta-analysis [19,60].
Our research found that AP þ MA is effective and prior to AP. No
systematic review regarding EA þ APA for the treatment of primary
insomnia. We found EA þ APA is better than IN, AP, EA, PBN, BA,
sham acupuncture, and usual treatment. EA could better control the
intensity of stimulation through extremely thin electrodes, and
may be a wider range of applications in the future [61]. Limited
evidence suggests that, compared with usual treatment, BA is no
difference in improving the effective rate and PSQI score. BA may
not be considered as a treatment strategy for primary insomnia
until more high-quality studies are available to demonstrate its
efficiency.
For TCM syndrome score, ESS, AIS and recurrence rate,
ACE þ MA and AP þ MA were better than other interventions on
TCM syndrome score. AP þ MA and FN had a significant reduction
than MA on ESS score reduction. MA was better than usual treat-
ment on AIS. ACE þ AP was better than AP on recurrence rate.
However, the number of studies on these outcome indicators is
very small, and we have less effective information. Twenty-two
studies reported adverse events. We found that there were no
serious adverse events related to acupuncture in all studies, con-
sisting unanimously with findings in previous studies [3]. There-
fore, we consider that the safety of acupuncture is reliable.
We found differences between therapies are small or insignifi-
cant and based-on low certainty of evidence. Only ACE is superior
to MA. And ACE, ACE þ MA, AP þ MA, FN and HPN are better than
EA in the network results. We consider there may be two condi-
tions. One condition is that this result may be reflect the real sit-
uation, only because possible risk of bias (especially considered
blinding) lower the certainty of the evidence. Another situation is
that the number of included studies is small, so the results cannot
reflect the differences between different therapies.
Meanwhile, when we assessed the evidence, we found that most
of the research evidence was low certainty of evidence, and the
main reason for the downgrade was risk of bias and imprecision.
Downgrading in the risk of bias is concentrated in adequate allo-
cation concealment and blinding. Previous study has shown that
most RCTs have unclear descriptions of allocation concealment

Table 1
Summary of results of adverse events for all interventions. The number is the number of people with various adverse events.

Intervention Sample size Hematoma Pain Headache Bleeding Dizziness Blood stasis Other

MA 914 39 10 14 10 8 3 Blood stasis (3), hand numbness (2), fainting (2),

sticking of needle (1)
FN 94 4 25 e 12 e e e
EA 656 1 1 3 e e e Hand numbness (1); upper respiratory infection
(24); dyspepsia (7); pruritus (1); others (8)
AP 123 e e e e e e Thirst and bitter taste in mouth (1)
ACE 200 e e e e e e Swelling (5)
ACE þ MA 30 e e e 2 e e e
ACE þ AP 93 e e e e e 7 Blood stasis (3)
SA/usual 1179 11 4 27 3 6 1 Local muscle convulsion (10), hand numbness
(1); worsening of insomnia (1); upper
respiratory infection (13); dyspepsia (4);
pruritus (1); others (5)

45
Y. Lu, H. Zhu, Q. Wang et al.
[62]. Although the impact of whether allocation concealment is
performed in the meta-analysis is not as large as expected, high-
quality RCTs are still needed in the field of Chinese medicine
[63,64]. For blinding, in acupuncture RCTs, because physicians must
operate according to the disease, making blinding difficult. Our
downgrade of imprecision is mainly due to crossing invalid values
and single small sample study. In our included studies, such as PSQI,
there are eight direct comparisons based on one study. In addition,
we think this is related to the complex features of TCM in-
terventions that might not be fully reflected by RCTs [65,66]. For
TCM interventions, pragmatic trials or observational studies using
real-world data are also important evidence pillar [67]. Therefore,
optimizing the integration of randomized and non-randomized
studies of interventions in evidence syntheses may be a more
optimized approach when there is no high certainty evidence from
RCTs or insufficient evidence from RCTs [68,69].
4.2. Strengths and limitations
This is an innovative network meta-analysis, which firstly
comprehensively compared the effect and safety of different
acupuncture therapies on primary insomnia based-on globally
available evidence. We used explicit eligibility criteria, study se-
lection, data extraction, risk of bias assessment, performing dupli-
cate assessment of study eligibility and evidence assessment. From
the network plots, we can find that only limited evidence compared
the differences between different acupuncture therapies. There-
fore, we use network meta-analysis method to provide indirect
evidence when there is no direct evidence. Meanwhile, the power
of evidence body can be enhanced by combining direct and indirect
evidence. We rated the certainty of evidence from network meta-
analysis using the latest advance of GRADE approach. We also
used an innovative classification scheme to interpret and present
the results in complex network and used PSQI as an example.
However, there are some limitations. First, because of the lack of
high-quality RCTs, many comparisons provided only low certainty
evidence. Second, the paucity of direct comparisons between
acupuncture-related interventions contributed to the low certainty
evidence because of serious risk of bias and imprecision. Third, we
do not find study focused on the potential costs associated with
acupuncture interventions. Forth, we do not use clinical important
decision threshold or minimally important difference (MID) to
decide the imprecision [70]. Furthermore, we do not perform
subgroup or meta-regression analysis because of limited evidence.
Meanwhile, incomplete reporting of patient important outcomes is
also a limitation for included RCTs. Future study should report
patient important outcomes or using the core outcome sets of
Chinese medicine [71].
4.3. Comparison with other studies
As said above, most systematic reviews on acupuncture therapy
of primary insomnia are based on direct comparison. Our research is
similar to a network meta-analysis that efficacy comparison of
different acupuncture treatments for primary insomnia [23]. The
research included 42 studies, containing 3304 participants, including
five acupuncture therapies (conventional acupuncture, electro-
acupuncture, scalp acupuncture, warm acupuncture, and electro-
acupuncture combined scalp acupuncture), and effectiveness rate as
primary outcome. The results showed that scalp acupuncture is the
most effective measure. The effectiveness of head penetration
needling, electroacupuncture and manual acupuncture has also been
46
Sleep Medicine 93 (2022) 39e48
confirmed in our research. However, compared with this research,
we have several differences. In terms of research methods, we have
included more studies, sample sizes, outcome indicators, and
concentrated on more acupuncture programs. Meanwhile, we use
GRADE approach to assess the certainty of evidence, improving the
transparency and usefulness of NMA results [72e74]. And we inno-
vate presentation of network meta-analysis results [54].
5. Conclusion
Based on the available evidence, compared with usual treat-
ment, most types of acupuncture therapy showed the improvement
of both subjective and objective sleep indices, especially acupoint
catgut embedding, auricular acupressure or auricular acupuncture
plus acupuncture, electroacupuncture plus acupoint application.
Differences between therapies were small or insignificant. But the
evidence body is usually low certainty in the field of acupuncture
for insomnia. Integrating randomized and non-randomized studies
in evidence syntheses is needed and future studies should enhance
the reporting of the patient important outcomes.
Author contributions
LG, JT, JN, ML, FY, XN and LL concepted and designed the study.
LG, JT, JN, ML, FY, XN, LL, YL, QW and YG designed the methodology.
LG, JT and JN administrated and validated the project. LG, ML, FY, XN
and LL supervise the project. LG, QW, HZ, YL and YG developed
search strategy. QW and HZ screened potential studies and reviews.
YL, CT and QW extracted data, assessed the risk of bias and certainty
of evidence. YL, QW and HL manage data. YL, QW, HL, LH and YL
analysis data. YL and QW wrote the first draft of the manuscript. LG,
YL, QW and HZ edited the final manuscript. All authors have
approved the final manuscript.
Data availability statement
The original contributions presented in the study are included in
the article/Supplementary Material; further inquiries can be
directed to the corresponding author.
Funding
This work was supported by the National Key R&D Program,
China National Centre for Biotechnology Development (No.
2019YFC1709805).
Conflict of interest
None of the authors have any conflict of interest to declare in
this study.
The ICMJE Uniform Disclosure Form for Potential Conflicts of
Interest associated with this article can be viewed by clicking on the
following link: https://doi.org/10.1016/j.sleep.2022.03.012.
Acknowledgments
Nil.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.sleep.2022.03.012.
Y. Lu, H. Zhu, Q. Wang et al. Sleep Medicine 93 (2022) 39e48

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