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Hindawi

Evidence-Based Complementary and Alternative Medicine


Volume 2020, Article ID 6137450, 17 pages
[Link]

Review Article
The Effectiveness of Acupuncture in Management of Functional
Constipation: A Systematic Review and Meta-Analysis

Lu Wang,1 Mingmin Xu ,1 Qianhua Zheng,1 Wei Zhang,2 and Ying Li 3

1
School of Acupuncture–Moxibustion and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
2
Office of Educational Administration, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
3
Graduate School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China

Correspondence should be addressed to Ying Li; liying@[Link]

Received 6 March 2020; Revised 18 May 2020; Accepted 1 June 2020; Published 17 June 2020

Academic Editor: Senthamil R. Selvan

Copyright © 2020 Lu Wang et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. The purpose of this study was to assess the effectiveness and safety of acupuncture for functional constipation (FC).
Methods. A rigorous literature search was performed in English (PubMed, Web of Science, the Cochrane Library, and EMBASE)
and Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), Wanfang database, and
China Science and Technology Journal (VIP)) electronic databases from their inception to October 2019. Included randomized
controlled trials (RCTs) compared acupuncture therapy with sham acupuncture or pharmacological therapies. The outcome
measures were evaluated, including the primary outcome of complete spontaneous bowel movement (CSBM) and secondary
outcomes of Bristol Stool Form Scale (BSFS), constipation symptoms scores (CSS), responder rate, the Patient Assessment of
Constipation Quality of Life (PAC-QOL) questionnaire, and safety evaluation. Meta-analysis was performed by using RevMan5.3.
Results. The merged data of 28 RCTs with 3525 participants indicated that acupuncture may be efficient for FC by increasing
CSBMs (p < 0.00001; MD � 0.84 [95% CI, 0.65 to 1.03]; I2 � 0%) and improving constipation symptoms (p � 0.03; SMD � −0.4
[95% CI, −0.78 to −0.03]; I2 � 74%), stool formation (p < 0.00001; MD � 0.24 [95% CI, 0.15 to 0.34]; I2 � 0%), quality of life
(p < 0.00001; N � 1, MD � −0.33 [95% CI, −0.45 to −0.21]), and responder rates (p � 0.02; RR � 2.16; [95% CI, 1.1 to 4.24];
I2 � 69%) compared with the effects of sham treatment. No increased risk of adverse events was observed (p � 0.44; RR � 1.18;
[95% CI, 0.77 to 1.81]; I2 � 0%). With regard to medication comparisons, the pooled data indicated that acupuncture was more
effective in increasing CSBMs (p � 0.004; MD � 0.53 [95% CI, 0.17 to 0.88]; I2 � 88%) and improving patients’ quality of life
(p < 0.00001; SMD � −0.73 [95% CI, −1.02 to −0.44]; I2 � 64%), with high heterogeneity. However, there were no significant
differences in responder rate (p � 0.12; RR � 1.31; [95% CI, 0.94 to 1.82]; I2 � 53%), BSFS (p � 0.5; MD � 0.17 [95% CI, −0.33 to
0.68]; I2 � 93%), or CSS (p � 0.05; SMD � −0.62 [95% CI, −1.23 to −0.01]; I2 � 89%). Regarding safety evaluation, acupuncture was
safer than medications (p < 0.0001; RR � 0.3; [95% CI, 0.18 to 0.52]; I2 � 30%). Conclusions. Current evidence suggests that
acupuncture is an efficient and safe treatment for FC. Acupuncture increased stool frequency, improved stool formation, al-
leviated constipation symptoms, and improved quality of life. However, the evidence quality was relatively low and the rela-
tionship between acupuncture and drugs is not clear. More high-quality trials are recommended in the future. PROSPERO
registration number: CRD42019143347.

1. Introduction not life-threatening, it has a very significant adverse impact


on quality of life and increases economic costs [3, 4]. Risk
Functional constipation (FC) is one of the common func- factors for FC include female sex, older age, and reduced
tional bowel disorders that affect approximately 14% of the caloric intake [5, 6]. These adverse effects make the man-
adult population worldwide [1]. One survey study indicated agement of constipation a major clinical issue.
that the most frequent symptoms of FC were decreased Many guidelines and reviews summarize stepwise clinical
defecation frequency, difficult stools, feelings of incomplete therapeutic approaches from appropriate lifestyle and dietary
evacuation, and abdominal discomfort [2]. Although FC is modifications to various drug administration, including
2 Evidence-Based Complementary and Alternative Medicine

osmotic agents, stimulant laxatives, prosecretory agents, sero- Table 1: The search strategy in PubMed.
tonin (5-HT4) receptor agonists, and probiotics, and so on Number Search items
[7, 8]. Anorectal biofeedback, nerve stimulation, and colonic
1 Functional constipation
surgery may be used to treat FC [9–11]. Although there are 2 Chronic functional constipation
many methods to choose from, the side effects of these methods 3 Chronic constipation
are notable, including diarrhea, bloating, nausea, and possible 4 Idiopathic constipation
cardiovascular adverse events [12–14]. As a result, many people, 5 Slow transit constipation
including those who do not improve with existing medications 6 Functional gastrointestinal disorder
or suffer many side effects, are interested in complementary 7 Functional defecatory disorder
alternative medicine. 8 Chronic severe functional constipation
According to a 2015 study, acupuncture and electro- 9 Constipation
acupuncture were the most commonly used complementary 10 FC
and alternative therapies for constipation, followed by herbal 11 CC
12 CSFC
medicine [15]. Acupuncture is an ancient Chinese medicine
13 Or 1–12
method in which acupuncture points on the skin are 14 Acupuncture
manually stimulated with needles. Acupuncture treats FC 15 Acupuncture therapy
via regulation of the nervous system and peripheral gas- 16 Acupuncture needle
trointestinal hormone contents [16, 17]. However, the 17 Manual acupuncture
current systematic review remained an uncertain conclusion 18 Electroacupuncture
whether acupuncture was effective in managing FC because 19 Needling
of the miscellaneous outcome measures and diagnostic 20 MA
criteria and lack of high-quality repeatable multicenter 21 EA
randomized controlled trials (RCTs) [18]. Therefore, we 22 Or 14–21
23 Randomized controlled trial
performed a systematic review to evaluate the effectiveness
24 Controlled clinical trial
and safety of acupuncture in the treatment of patients with
25 Randomized
FC via unification of measurement outcomes and inclusion 26 Randomly
criteria and the inclusion of high-quality RCTs. 27 Trial
28 Or 23–27
2. Methods 29 Exp animals/not humans
30 28 not 29
This systematic review was registered in the PROSPERO 31 13 and 22 and 30
registry (CRD42019143347), and the protocol was described
previously [19]. The PRISMA guidelines and the recom- Rome IV/III/II criteria, regardless of demographic
mendations of the Cochrane Handbook for Systematic characteristics (ethnicity, comorbidity, gender, age)
Reviews of Interventions were complied with this systematic and severity of disease were included.
review and meta-analysis (Table S1) [20, 21]. (2) Study design: The trials were RCTs that used a two-,
three-, or four-arm parallel design regardless of blinding.
2.1. Search Strategy. Two reviewers (WZ and QHZ) searched (3) Types of interventions: The intervention group was
the databases from inception to October 2019, including four treated with acupuncture or electroacupuncture
English databases (the PubMed, Web of Science, Cochrane (EA), regardless of the number of acupuncture
Library, and EMBASE) and four Chinese databases (China points, frequency, and courses of treatment. The
National Knowledge Infrastructure (CNKI), Chinese Biological control groups received no treatment, placebo
Medical (CBM), China Science and Technology Journal (VIP), acupuncture, sham acupuncture (SA), conventional
and Wanfang Data Chinese databases). We used the following medication, or placebo control.
terms: (1) “acupuncture,” “manual acupuncture,” “electro- (4) Outcome measures: We limited the outcome mea-
acupuncture,” “acupuncture therapy,” or “acupuncture points,” sures to complete spontaneous bowel movement
combined with (2) “constipation,” “functional constipation,” (CSBM), Bristol Stool Form Scale (BSFS), responder
“colonic inertia,” “dyschezia,” “astriction,” “obstipation,” or rate, constipation symptoms scores (CSS), the Pa-
“slow transit constipation.” (See Table 1, for the search terms tient Assessment of Constipation Quality of Life
and strategy.) Because of the language restriction of our re- (PAC-QOL) questionnaire, and safety evaluation.
searchers, only studies published in English and Chinese were
included.
2.2.2. Exclusion Criteria
2.2. Study Selection (1) Crossover trials, uncontrolled trials, quasi-ran-
domized trials, reviews, case reports, and animal
2.2.1. Inclusion Criteria experimental research studies were excluded.
(1) Participants: Patients over the age of 18 years who (2) Studies with participants that included special
were diagnosed with FC using guidelines or the populations, such as pregnant women, lactating
Evidence-Based Complementary and Alternative Medicine 3

women, or those diagnosed with constipation due to was defined as the number of responders having at least
irritable bowel syndrome, were excluded. three CSBMs per week divided by the total number of
(3) We excluded trials in which the controls received participants in each group. The PAC-QOL scored the effects
acupuncture in combination with other methods, of constipation on physical discomfort, psychosocial dis-
such as moxibustion, herbs, or medication and comfort, anxiety, concerns, and satisfaction in their daily
conventional medications that were not Western lives [24]. Higher scores indicated more defects or dissat-
medicine, such as Chinese medicine, Tibetan med- isfaction. Safety evaluation was assessed using the adverse
icine, and Zhuang medicine. event reported in the studies.
(4) Trials that compared different points or forms of
acupuncture were also excluded. 2.5. Data Analysis. The Review Manager software program
(5) We excluded low-quality trials that had a clear risk of (version 5.3) was used for data synthesis. For continuous
bias, such as a lack of randomized methods and variables, such as CSBM, BSFS, CSS, and PAC-QOL, the
incomplete data. mean difference (MD) or standard mean difference (SWD)
(6) Duplicate publications and studies with incomplete with 95% confidence interval (CI) was used for analysis. For
data were also excluded. dichotomous data, such as the rates of responders and
adverse events, the relative risk (RR) with 95% CI was
utilized for analysis. Some studies reported change-from-
2.3. Data Extraction and Quality Assessment. Two of the baseline values instead of after-treatment values. We cal-
authors (MMX and LW) reviewed all titles and abstracts culated the after-treatment values, assuming a correlation
independently to determine the eligibility of articles. Ar- coefficient of 0.4 between baseline values and after-treatment
gument between the two reviewers was solved via discussion values according to the Cochrane handbook [25]. For studies
and arbitration by a third reviewer (YL). The two authors that satisfied the predefined inclusion criteria with multiple
made a final judgment by reading the full text of the intervention groups, if the multiple intervention groups used
remaining articles. A standardized data extraction form was different acupuncture methods, we merged the data into a
used to extract detailed data from each selected study. The unified acupuncture group data. If the multiple intervention
extraction information was collected according to a fixed groups were different comparison groups, we implemented
protocol: study sites, total numbers, numbers of acupuncture pairwise comparisons. For missing data, we contacted the
and control participants, mean age, mean constipation corresponding authors via e-mail, otherwise the results were
duration, treatment duration, and outcomes. Missing in- excluded. The magnitude of heterogeneity was measured
formation about the included trials was obtained by con- using the I2 statistic: when I2 < 50%, a fixed-effects model will
tacting the correspondent authors via e-mail. be used for pooled data; and when I2 ≥ 50%, a random-effects
The Cochrane risk of bias tool was used to assess bias in model was used. For each merged analysis, a heterogeneity
each study included by the two reviewers (LW and WZ). The test was performed using the chi-squared statistic. If
risk of bias domains included random sequence generation, I2 ≥ 50%, the synthesized studies were considered an indi-
allocation concealment, blinding of participants and per- cator of a substantial level of heterogeneity. Subgroup or
sonnel, blinding of outcome assessment, incomplete out- sensitivity analysis was performed to identify the cause.
come data, selective reporting, and other bias. The risk of Subgroup analyses identified the possible factors that con-
bias in each domain was rated as “low,” “high,” or “unclear.” tributed to the heterogeneity, such as different acupuncture
Disagreements were resolved via consultation with the third stimulation parameters, different control groups, partici-
reviewer (YL). Finally, we evaluated the quality of evidence pants’ age, or disease course. And we evaluated publication
for the outcomes (acupuncture vs. SA) of the included bias by using funnel plots (n > 10).
studies in our review using the Grading of Recommenda-
tions Assessment, Development, and Evaluation (GRADE)
guidelines [22]. 3. Results
3.1. Search Results. According to the search strategy, a total
2.4. Outcome Assessment. The primary outcome was CSBM. of 1673 articles were identified. After duplicates were re-
Secondary outcomes were BSFS, CSS, responder rate, PAC- moved, 1131 articles were further evaluated using the eli-
QOL, and safety evaluation. The time point of all results was gibility criteria. Then, 116 articles were eligible for full-text
after treatment. A CSBM was defined as a bowel movement evaluation after screening the titles and abstracts. We also
with the sense of complete evacuation that occurred without excluded 86 articles for the following reasons: including IBS
the use of any medication or other methods to assist def- patients, no interested outcome indicator, repeated pub-
ecation in the previous 24 hours. The BSFS is a seven-hi- lished data, not RCT, and low quality. Eventually, we in-
erarchy scale, with scores of 1–2 indicating constipation, 3–5 cluded 30 studies in our system review [26–55]. Although 30
indicating normal stool, and 6–7 indicating diarrhea. The articles were included after screening, actually only 28 re-
CSS assessed patients’ eight constipation-related symptoms, lated RCTs (3525 participants) were extracted because data
including straining, endless sensation of defecation, bowel of 4 articles were from the same two RCTs (Peng, 2013; Mao,
sound, abdominal pain, abdominal bloating, stool consis- 2017 (2)), respectively [39, 40, 49, 50]. After reading the full
tency, diarrhea, and fecal incontinence [23]. Responder rate text and analyzing the time period of study, we found that
4 Evidence-Based Complementary and Alternative Medicine

the outcomes from Mao, 2017 (2) were selectively reported (p < 0.0001; RR � 0.3; [95% CI, 0.18 to 0.52]; I2 � 30%)
in 2016 and 2017 separately. The same selective reporting is (Figures 9–14).
the RCT of Peng, 2013. The search process was showed in The sensitivity analysis showed that heterogeneities in
Figure 1. CSBM (p < 0.00001; MD � 0.37 [95% CI, 0.22 to 0.52 ];
I2 � 27%), PAC-QOL (p < 0.00001; SMD � −0.6 [95% CI,
−0.82 to −0.39]; I2 � 31%), and responder rate (p � 0.01;
3.2. Characteristics of the Studies. The included studies came RR � 1.45; [95% CI, 1.08 to 1.95]; I2 � 0%) were reduced
from Korea and China and were published between 2010 and significantly after the removal of 1 RCT [36, 43, 53].
2019. The diagnostic criteria of one RCT were the guidelines for However, we did not find a clear source of heterogeneity for
clinical research [44], and the other RCTs were Rome [Link] CSS and BSFS with an I2 statistic that ranged from 80% to
was 1 four-arm RCT [55], 5 three-arm RCTs [49–54], and 23 93% in subgroup analyses, such as different acupuncture
two-arm RCTs [26–48]. The treatment duration was set for 2 stimulation parameters, different drug groups, age, and
weeks in 2 studies [32, 46], 3 weeks in 1 study [47], 4 weeks in disease course.
18 studies [27, 30, 31, 33–37, 42, 44, 45, 48–55], and 8 weeks in
7 studies[26, 28, 29, 38–41, 43]. For these 28 trials, 10 trials
reported CSBM [26–28, 36, 38–43, 46], 13 trials reported BSFS 3.6. Subgroup Analysis for Medication
[27–29, 34, 35, 38–43, 47, 48, 53], 9 trials presented responder
3.6.1. CSBM. Acupuncture had a better effect than pruca-
rate [26, 28, 29, 38–41, 43, 47, 53], 6 trials presented CSS
lopride (p � 0.0004; WMD � 0.32 [95% CI, 0.14 to 0.5];
[30, 45, 48–52], 10 trials mentioned PAC-QOL
I2 � 29%). However, sensitivity analysis found no significant
[28, 32, 33, 37, 38, 41, 43, 44, 46, 53], and 15 trials mentioned
difference between acupuncture and prucalopride after the
safety evaluation [26–33, 49–55]. Table 2 summarizes the other
removal of one study (p � 0.1; WMD � 0.18 [95% CI, −0.04
parameters of the included trials.
to 0.4]; I2 � 0%). Two studies showed that acupuncture had a
better performance than mosapride and lactulose
3.3. Risk of Bias Assessment. Figure 2 summarizes the risk of (Figure 15).
bias in the 28 RCTs. Blinding of participants and personnel
and incomplete outcome data may be the major reasons for 3.6.2. BSFS. Subgroup analysis showed a significant increase
selection bias and performance bias. Many studies were in the acupuncture groups’ performance on BSFS relative to
associated with an unclear risk of bias for blinding of the lactulose group (p < 0.00001; WMD � 0.62 [95% CI, 0.37
outcome assessment, selective reporting, and other possible to 0.88]; I2 � 0%) and the mosapride group (p � 0.005;
bias. WMD � 0.62 [95% CI, 0.19 to 1.05]; I2 � 61%). Acupuncture
was not significantly different than the highly heterogeneous
comparison with prucalopride (p � 0.53; WMD � −0.29
3.4. Acupuncture vs SA. The merged data indicated that the [95% CI, −1.19 to 0.62]; I2 � 95%) (Figure 16).
acupuncture group exhibited significantly greater efficacy
than the SA group in increasing CSBMs (p < 0.00001;
MD � 0.84 [95% CI, 0.65 to 1.03]; I2 � 0%) and improving 3.6.3. CSS. There was no evidence of a benefit in reducing
stool formation (p < 0.00001; MD � 0.24 [95% CI, 0.15 to CSS in the acupuncture group compared to the lactulose
0.34]; I2 � 0%), responder rates (p � 0.02; RR � 2.16; [95% group (p � 0.05; SMD � −0.62 [95% CI, −1.23 to −0.01];
CI, 1.1 to 4.24]; I2 � 69%), constipation symptoms (p � 0.03; I2 � 89%). However, sensitivity analysis found that acu-
SMD � −0.4 [95% CI, −0.78 to −0.03]; I2 � 74%), and the puncture was superior to lactulose in reducing CSS after the
quality of life (p < 0.00001; N � 1, SMD � −0.33 [95% CI, removal of one study [48] (p � 0.008; SMD � −0.87 [95% CI,
−0.45 to −0.21]). No increased risk of adverse events was −1.52 to −0.23]; I2 � 88%) (Figure 17).
observed (p � 0.44; RR � 1.18; [95% CI, 0.77 to 1.81];
I2 � 0%). Sensitivity analysis showed that acupuncture 3.6.4. PAC-QOL. Subgroup analysis revealed that acu-
produced a significant decrease in CSS after the removal of puncture produced a significant benefit compared with
one study [30] (p � 0.02; SMD � −0.23 [95% CI, −0.42 polyethylene glycol (p � 0.0002; SMD � −0.49 [95% CI,
to −0.04]; I2 � 0%) (Figures 3–8). −0.75 to −0.23]; I2 � 0%) and mosapride (p � 0.02;
SMD � −0.47 [95% CI, −0.85 to −0.08]; I2 � 0%). Two studies
reported that the acupuncture group had a lower score than
3.5. Acupuncture vs Medication. The pooled data indicated
the cisapride group (p � 0.008, N � 1, n � 60, 95% CI, −1.22
that acupuncture was more effective in increasing CSBMs
to −0.18) and lactulose group (p < 0.0001, N � 1, n � 60, 95%
(p � 0.004; MD � 0.53 [95% CI, 0.17 to 0.88]; I2 � 88%) and
CI, −1.79 to −0.68). However, high heterogeneity was found
improving patients’ quality of life (p < 0.00001; SMD � −0.73
in comparisons with prucalopride (p � 0.04; SMD � −1.07
[95% CI, −1.02 to −0.44]; I2 � 64%) than the medication
[95% CI, −2.08 to −0.05]; I2 � 86%) (Figure 18).
groups. However, there were no significant differences in
responder rate (p � 0.12; RR � 1.31; [95% CI, 0.94 to 1.82];
I2 � 53%), BSFS (p � 0.5; MD � 0.17 [95% CI, −0.33 to 0.68]; 3.6.5. Responder Rate. Prucalopride (p � 0.07; RR � 1.25;
I2 � 93%), and CSS (p � 0.05; SMD � −0.62 [95% CI, −1.23 [95% CI, 0.98 to 1.6]; I2 � 14%), mosapride (N � 1, n � 60,
to −0.01]; I2 � 89%). Acupuncture was safer than medication p � 0.31; [95% CI, 0.94 to 1.23]), and lactulose (N � 1, n � 45,
Evidence-Based Complementary and Alternative Medicine 5

1673 records were identified through


database searching. details as below:
Pubmed (n = 150);
Embase (n = 121);
Cochrane Library (n = 226);
Web of Science (n = 135)
CBM (n = 172);
CNKI (n = 330);
Wangfang (n = 482);
VIP (n = 57)

Duplicates (n = 542)

Records after duplicates removed Records excluded after reviewing


(n = 1131) titles and abstracts, reasons as below:
Reviews (n = 94)
Animal experiments (n = 67)
Protocols (n = 30)
Nonadult (n = 10)
Nonstandard RCTs (n = 6)
Not functional constipation (n = 512)
Not the comparision and intervention
of interest (n = 294)
Others (n = 2)

Full text screened for eligibility


(n = 116) Records were excluded after
reviewing the full text, reasons list
as below:
Not the outcome of interest (n = 41)
IBS (n = 2)
data duplication (n = 36)
Nonstandard RCTs (n = 3)
Low quality trials (n = 4)
30 articles from 28 RCTs included in
analysis

Figure 1: Flow diagram of the selection process.

p � 0.05; [95% CI, 1 to 2.15]) failed to achieve statistical evaluation, low for CSBM, BSFS, and responder rate, and
significance (Figure 19). very low for CSS.

4. Discussion
3.6.6. Safety Evaluation. The subgroup analysis suggested
that acupuncture produced no significant difference com- 4.1. Principal Results. The present review examined 28 RCTs
pared with polyethylene glycol (p � 0.21; RR � 0.4; [95% CI, involving 3525 participants that studied the effects of acu-
0.1 to 1.67]; I2 � 43%). Methodologically, acupuncture was puncture treatment on the management of FC. Acupuncture
safer than lactulose (p � 0.0009; RR � 0.24; [95% CI, 0.1 to was associated with the magnitude of clinically relevant
0.56]; I2 � 23%) and mosapride (p � 0.01; RR � 0.36; [95% effects in reducing the severity of FC compared with SA and
CI, 0.16 to 0.8]; I2 � 60%) (Figure 20). pharmacological treatments (polyethylene glycol, pruca-
lopride, mosapride, cisapride, and lactulose). With regard to
SA comparison, acupuncture treatment may not increase the
3.7. GRADE Evaluation. We only evaluated the qualities of risk of adverse events and may be more efficient in in-
the outcomes that compared acupuncture with SA, and the creasing CSBMs, improving stool formation, alleviating
quality of that evidence ranged from very low to moderate constipation symptoms, and promoting the quality of life
(Table 3). The major reasons for downgrading the evidence and responder rates. This study found that SA was inferior to
quality were inconsistency and reporting bias. The levels of real acupuncture for patients, which was consistent with
evidence quality were moderate for PAC-QOL and safety previous findings [18, 56, 57]. However, the evidence quality
6 Evidence-Based Complementary and Alternative Medicine

Table 2: Characteristics of included studies.


Study Participants’ age Disease course
Author n Diagnostic criteria Participants Duration Outcomes
sites (years, M ± SD) (M ± SD)
Acupuncture vs sham electroacupuncture
Treatment:
Da et al. 37.94 ± 18.06 139.59 ± 112.68 mos
1 67 Rome III 34 8 weeks ①③⑥
[26]
Control: 33 37.00 ± 17.89 106.21 ± 91.98 mos
Lee et al. Treatment: 14 49.6 ± 12.7 Not reported
1 29 Rome III 4 weeks ①②⑥
[27] Control: 15 50.0 ± 10.5 Not reported
Treatment:
Liu et al. 47.01 ± 16.5 130.8 ± 122.6 mos
15 1075 Rome III 536 8 weeks ①②③⑤⑥
[28]
Control: 539 47.33 ± 15.8 132.7 ± 127.0 mos
Treatment:
49 ± 34.5 68.5 ± 94.5 mos
Wu [29] 1 120 Rome III 60 8 weeks ②③⑥
Control: 60 52.63 ± 12.9 101 ± 102.2 mos
Treatment:
Xue et al. 48.85 ± 13.30 7.65 ± 6.48 yrs
1 96 Rome III 48 4 weeks ④⑥
[30]
Control: 48 45.25 ± 11.28 8.48 ± 5.76 yrs
Acupuncture vs polyethylene glycol
Treatment:
48.80 ± 8.18 5.06 ± 3.66 mos
Chen [31] 1 61 Rome III 30 4 weeks ⑥
Control: 31 48.58 ± 8.14 4.94 ± 3.68 mos
Treatment:
74.5 1 mos
Mao [32] 1 62 Rome III 30 2 weeks ⑤⑥
Control: 32 73 1 mos
Treatment:
48.03 ± 17.19 24.52 ± 11.32 mos
Ou [33] 1 170 Rome III 84 4 weeks ⑤⑥
Control: 86 46.64 ± 15.71 23.5 ± 10.36 mos
Acupuncture vs mosapride
Treatment:
Ding et al. 34.83 ± 11.76
1 63 Rome III 33 5.71 ± 2.54 yrs 4 weeks ②
[34]
Control: 30
Treatment:
Lian et al. 26.85 ± 8.27 3.44 ± 2.56 yrs
1 63 Rome III 33 4 weeks ②
[35]
Control: 30 27.60 ± 7.86 2.92 ± 2.24 yrs
Treatment:
Wang et al. 47.8 ± 10.1 7. 6 ± 6.4 yrs
1 68 Rome III 34 4 weeks ①
[36]
Control: 34 46. 6 ± 11. 0 8.1 ± 5.9 yrs
Treatment:
28.08 ± 13.42 95.43 ± 103.03 mos
Wang [37] 1 54 Rome III 37 4 weeks ⑤
Control: 17 27.59 ± 9.70 92.00 ± 78.48 mos
Acupuncture vs prucalopride
Treatment:
40.48 ± 2.96 110.76 ± 17.4 mos
Dai [38] 1 60 Rome III 30 8 weeks ①②③⑤
Control: 30 42.80 ± 3.92 150.48 ± 30.84 mos
Treatment:
Mao 44.85 ± 7.71 3.78 ± 2.12 yrs
1 56 Rome III 28 8 weeks ①②③
[39, 40]
Control: 28 46.95 ± 9.83 3.88 ± 2.36 yrs
Treatment:
51.40 ± 12.90 Not reported
Song [41] 1 39 Rome III 20 8 weeks ①②③⑤
Control: 19 49.16 ± 12.31 Not reported
Treatment:
Wang et al. 46 ± 7 4.52 ± 2.36 yrs
1 60 Rome III 30 4 weeks ①②
[42]
Control: 30 47 ± 8 4.64 ± 2.65 yrs
Treatment: 19 41.53 ± 16.15 76.68 ± 7.75 mos
Wang [43] 1 38 Rome III 8 weeks ①②③⑤
Control: 19 35.29 ± 13.26 76 ± 4.93 mos
Acupuncture vs cisapride
Treatment:
Zhou et al. The guidelines for 37. 36 ± 10. 32 2. 54 ± 1. 63 yrs 4 weeks ⑤
1 60 30
[44] clinical research
Control: 30 39. 58 ± 11. 63 2. 72 ± 1. 76 yrs
Evidence-Based Complementary and Alternative Medicine 7

Table 2: Continued.
Study Participants’ age Disease course
Author n Diagnostic criteria Participants Duration Outcomes
sites (years, M ± SD) (M ± SD)
Acupuncture vs lactulose
Treatment:
39.14 ± 14.45 115.18 ± 108.08 mos
Jin [45] 1 37 Rome III 22 4 weeks ④
Control: 15 45.13 ± 17.09 157.4 ± 142.24 mos
Treatment:
Liu et al. 53. 13 ± 9. 65 3.70 ± 2. 54 yrs
1 60 Rome III 30 2 weeks ①⑤
[46]
Control: 30 52.76 ± 8.87 3.96 ± 2.68 yrs
Ruan et al. Treatment: 21 68 ± 9 17.90 ± 9.77 mos
1 45 Rome III 3 weeks ②③
[47] Control: 24 69 ± 8 16.92 ± 10.04 mos
Treatment:
64.87 ± 4.208 5.27 ± 3.51 yrs
Shi [48] 1 60 Rome III 30 4 weeks ②④⑥
Control: 30 66.27 ± 3.513 5.5 ± 3.94 yrs
Acupuncture vs sham acupuncture vs lactulose
Treatment:
53 ± 13 125.1 ± 128.6 mos
Peng et al. 64
3 128 Rome III 4 weeks ④⑥
[49, 50] Control A: 33 52 ± 17 118 ± 105.8 mos
Control B: 31 59 ± 12 97.8 ± 123 mos
Treatment:
48.8 ± 13.3 7.65 ± 6.48 yrs
Wang et al. 48
1 95 Rome III 4 weeks ④⑥
[51] Control A: 24 40.8 ± 10.0 9.46 ± 5.89 yrs
Control B: 23 44.6 ± 15.2 7.65 ± 5.65 yrs
Treatment:
45.88 ± 16.85 110.84 ± 99.85 mos
228
Wu et al. Control A:
5 475 Rome III 46.25 ± 16.81 109.25 ± 100.70 mos 4 weeks ④⑥
[52] 112
Control B:
44.12 ± 17.48 111.04 ± 110.15 mos
115
Acupuncture vs mosapride vs mosapride & sham electroacupuncture
Treatment:
35.26 ± 19.07 8.88 yrs
30
Xu [53] 1 90 Rome III 4 weeks ②③⑤⑥
Control A: 30 35.42 ± 15.28 8.71 yrs
Control B: 30 36.00 ± 17.20 8.83 yrs
Low intensity acupuncture vs high intensity acupuncture vs mosapride
Treatment A:
34.00 ± 15.62 70.44 ± 85.53 mos
58
Wu et al.
3 190 Rome III Treatment B: 4 weeks ⑥
[54] 37.20 ± 18.19 86.29 ± 104.06 mos
65
Control: 67 43.60 ± 17.90 68.09 ± 74.13 mos
Shu-mu vs He vs Shu-mu-he vs mosapride
Treatment A:
61 (16) 130 mos
19
Treatment B:
Wu et al. 53 ± 12 123 mos
1 104 Rome III 34 4 weeks ⑥
[55]
Treatment C:
56 ± 9 217.35 mos
26
Control: 25 55 ± 11 130 mos
Notes: M ± SD, the mean ± standard deviation; mos, months; yrs, years; ① complete spontaneous bowel movement (CSBM); ② Bristol Stool Form Scale (BSFS); ③
responder rate; ④ constipation symptoms scores (CSS); ⑤ Patient Assessment Of Constipation Quality Of Life (PAC-QOL) questionnaire; ⑥ safety evaluation.

was relatively low because of inconsistency and reporting Previous studies showed that many factors influenced
bias. Our meta-analysis showed that acupuncture may be the efficacy of acupuncture, such as age, comorbidity,
more effective than pharmacological treatment in increasing gender, disease severity, stimulation of acupuncture, ex-
weekly CSBMs and improving the quality of life and re- pectations of patients, and doctor-patient interaction, which
sponder rate. The data suggested that acupuncture caused may be sources of heterogeneity [58–60]. However, due to
fewer adverse events. However, no significant benefits in the inability to obtain more relevant data, we cannot analyze
stool formation or clinical symptoms of FC were found in based on relevant influencing factors. The present study only
patients who received acupuncture compared with drug with found that the heterogeneity may be caused by different
high heterogeneity. control group. There were two outcomes (CSS and BSFS)
8 Evidence-Based Complementary and Alternative Medicine

Random sequence generation (selection bias)


Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias

0 25 50 75 100
(%)
Low risk of bias
Unclear risk of bias
High risk of bias
Wang, 2016 (2)

Mao, 2017 (2)


Wu, 2014 (2)
Wu, 2014 (1)
Wu, 2014 (3)

Liu, 2016 (2)


Wang, 2017

Wang, 2016
Wang, 2013
Wang, 2010

Chen, 2019
Zhou, 2013

Ruan, 2018

Ding, 2017
Song, 2016

Peng, 2013

Mao, 2017

Lian, 2014
Xue, 2015

Dai, 2016
Wu, 2017

Lee, 2018
Liu, 2016
Ou, 2012
Shi, 2017

Da, 2015
Xu, 2015

Jin, 2010
? + + + + + + + + + + + + + + + + + + + + + + ? ? + + + Random sequence generation (selection bias)
? + + + + + + ? + + + + + ? ? + ? + + ? + + + ? ? + + ? Allocation concealment (selection bias)
– – + + + + – ? – – – – – – – – – – – – + – + – – + + – Blinding of participants and personnel (performance bias)
? + ? + + + + ? + ? + ? ? ? ? + ? + + ? + ? + ? ? + ? ? Blinding of outcome assessment (detection bias)
+ + + + + + + + + + + + + + – + + + – + + + ? – ? + + + Incomplete outcome data (attrition bias)
? ? + ? + ? ? ? ? – ? ? ? ? ? ? ? ? ? ? + – ? ? – – ? ? Selective reporting (reporting bias)
? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Other bias

Figure 2: Risk of bias assessment.

Acupuncture SA Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, fixed, 95% CI IV, fixed, 95% CI
Da, 2015 2 1.67 34 1.33 1.09 33 8.1 0.67 [–0.00, 1.34]
Lee, 2018 3.21 3.83 14 3.47 2.45 15 0.7 –0.26 [–2.62, 2.10]
Liu, 2016 2.15 1.8 536 1.29 1.55 539 91.2 0.86 [0.66, 1.06]

Total (95% CI) 584 587 100.0 0.84 [0.65, 1.03]


Heterogeneity: chi2 = 1.12, df = 2 (p = 0.57); I2 = 0%
Test for overall effect: Z = 8.55 (p < 0.00001) –4 –2 0 2 4
SA Acupuncture

Figure 3: Forest plot for CSBM (acupuncture vs SA).

Acupuncture SA Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, fixed, 95% CI IV, fixed, 95% CI
Lee, 2018 4.17 1.48 14 3.47 1.33 15 0.9 0.70 [–0.33, 1.73]
Liu, 2016 3.45 0.63 536 3.22 1.04 539 88.5 0.23 [0.13, 0.33]
Wu, 2014 (1) 3.56 0.83 60 3.24 0.83 60 10.6 0.32 [0.02, 0.62]

Total (95% CI) 610 614 100.0 0.24 [0.15, 0.34]


Heterogeneity: chi = 1.08, df = 2 (p = 0.58); 2 I2 = 0%
Test for overall effect: Z = 4.94 (p < 0.00001) –2 –1 0 1 2
SA Acupuncture

Figure 4: Forest plot for BSFS (acupuncture vs SA).

Acupuncture SA Weight Risk ratio Risk ratio


Study or subgroup
Events Total Events Total (%) M-H, random, 95% CI M-H, random, 95% CI
Da, 2015 8 34 1 33 9.2 7.76 [1.03, 58.70]
Liu, 2016 168 536 65 539 51.3 2.60 [2.00, 3.37]
Wu, 2014 (1) 19 60 15 60 39.5 1.27 [0.71, 2.25]

Total (95% CI) 630 632 100.0 2.16 [1.10, 4.24]


Total events 195 81
Heterogeneity: tau2 = 0.21; chi2 = 6.43, df = 2 (p = 0.04); I2 = 69%
Test for overall effect: Z = 2.25 (p = 0.02) 0.01 0.1 1 10 100
SA Acupuncture

Figure 5: Forest plot for responder rate (acupuncture vs SA).


Evidence-Based Complementary and Alternative Medicine 9

Acupuncture SA Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Peng, 2013 8.08 3.769 63 8.1 3.229 31 23.8 –0.01 [–0.44, 0.42]
Wang, 2010 5.15 2.32 48 6.27 2.75 23 21.3 –0.45 [–0.95, 0.05]
Wu, 2014 (2) 8.25 2.18 228 8.75 1.62 112 30.9 –0.25 [–0.47, –0.02]
Xue, 2015 5.15 2.33 48 7.81 3.1 48 24.0 –0.96 [–1.39, –0.54]

Total (95% CI) 387 214 100.0 –0.40 [–0.78, –0.03]


Heterogeneity: tau2 = 0.10; chi2 = 11.42, df = 3 (p = 0.010); I2 = 74%
Test for overall effect: Z = 2.13 (p = 0.03) –4 –2 0 2 4
Acupuncture SA

Figure 6: Forest plot for CSS (acupuncture vs SA).

Acupuncture SA Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Liu, 2016 1.88 0.73 536 2.12 0.71 539 100.0 –0.33[–0.45, –0.21]

Total (95% CI) 536 539 100.0 –0.33 [–0.45, –0.21]


Heterogeneity: not applicable
–100 –50 0 50 100
Test for overall effect: Z = 5.42 (p < 0.00001)
Acupuncture SA

Figure 7: Forest plot for PAC-QOL (acupuncture vs SA).

Acupuncture SA Weight Risk ratio Risk ratio


Study or subgroup
Events Total Events Total (%) M-H, fixed, 95% CI M-H, fixed, 95% CI
Da, 2015 2 34 1 33 2.8 1.94 [0.18, 20.40]
Lee, 2018 4 14 4 15 10.7 1.07 [0.33, 3.48]
Liu, 2016 31 536 24 539 66.1 1.30 [0.77, 2.18]
Peng, 2013 2 63 0 31 1.8 2.50 [0.12, 50.54]
Wang, 2010 0 48 0 23 Not estimable
Wu, 2014 (1) 0 60 0 60 Not estimable
Wu, 2014 (2) 6 228 5 112 18.5 0.59 [0.18, 1.89]

Total (95% CI) 983 813 100.0 1.18 [0.77, 1.81]


Total events 45 34
Heterogeneity: chi2 = 1.93, df = 4 (p = 0.75); I2 = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 0.78 (p = 0.44)
SA Acupuncture

Figure 8: Forest plot for safety evaluation (acupuncture vs SA).

Acupuncture Medication Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Dai, 2016 1.92 0.88 30 1.62 0.63 30 15.1 0.30 [–0.09, 0.69]
Liu, 2016 (2) 1.58 0.66 30 1.02 0.49 30 16.3 0.56 [0.27, 0.85]
Mao, 2017 (2) 2.63 0.53 20 2.56 0.48 20 16.0 0.07 [–0.24, 0.38]
Song, 2016 2.73 0.18 20 2.27 0.24 19 17.8 0.46 [0.33, 0.59]
Wang, 2016 3.89 0.86 34 2.36 0.39 34 16.0 1.53 [1.21, 1.85]
Wang, 2016 (2) 2.69 2.04 19 2.31 2.01 19 5.4 0.38 [–0.91, 1.67]
Wang, 2017 2.21 0.89 30 1.98 1.09 30 13.4 0.23 [–0.27, 0.73]

Total (95% CI) 183 182 100.0 0.53 [0.17, 0.88]


Heterogeneity: tau2 = 0.18; chi2 = 50.22, df = 6 (p < 0.00001); I2 = 88%
Test for overall effect: Z = 2.88 (p = 0.004) –4 –2 0 2 4
Medication Acupuncture

Figure 9: Forest plot for CSBM (acupuncture vs medication).

without an apparent source of heterogeneity compared outcome indicators, and statistical methods may be the
between acupuncture and medication. Our careful data reasons for heterogeneity. For example, different types of
analysis suggested that small sample size, the specificity of variables, such as considering the BSFS as a continuous or
10 Evidence-Based Complementary and Alternative Medicine

Acupuncture Medication Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Dai, 2016 3.18 0.68 30 2.99 0.32 30 10.6 0.19 [–0.08, 0.46]
Ding, 2017 4.08 1.26 33 3.11 1.15 30 9.5 0.97 [0.37, 1.57]
Lian, 2014 3.97 0.64 33 3.23 0.8 30 10.3 0.74 [0.38, 1.10]
Mao, 2017 (2) 3.4 0.75 20 4.9 1.02 20 9.6 –1.50 [–2.05, –0.95]
Ruan, 2018 2.43 0.5 21 1.88 0.61 24 10.4 0.55 [0.23, 0.87]
Shi, 2017 4.27 0.58 30 3.53 0.97 30 10.2 0.74 [0.34, 1.14]
Song, 2016 4.61 0.97 20 3.13 1.03 19 9.3 1.48 [0.85, 2.11]
Wang, 2016 (2) 3.22 0.48 19 3.37 0.83 19 10.1 –0.15 [–0.58, 0.28]
Wang, 2017 3.43 0.65 30 4.85 1.02 30 10.1 –1.42 [–1.85, –0.99]
Xu, 2015 3.44 0.9 30 3.26 0.97 30 9.9 0.18 [–0.29, 0.65]

Total (95% CI) 266 262 100.0 0.17 [–0.33, 0.68]


Heterogeneity: tau2 = 0.62; chi2 = 134.74, df = 9 (p < 0.00001)); I2 = 93%
Test for overall effect: Z = 0.67 (p = 0.50) –4 –2 0 2 4
Medication Acupuncture

Figure 10: Forest plot for BSFS (acupuncture vs medication).

Experimental Control Weight Risk ratio Risk ratio


Study or subgroup
Events Total Events Total (%) M-H, random, 95% CI M-H, random, 95% CI
Dai, 2016 10 30 8 30 12.5 1.25 [0.57, 2.73]
Mao, 2017 (2) 6 20 5 20 8.5 1.20 [0.44, 3.30]
Ruan, 2018 18 21 14 24 26.0 1.47 [1.00, 2.15]
Song, 2016 8 20 2 19 4.8 3.80 [0.92, 15.67]
Wang, 2016 (2) 8 19 6 19 11.1 1.33 [0.57, 3.11]
Xu, 2015 29 30 27 30 37.0 1.07 [0.94, 1.23]

Total (95% CI) 140 142 100.0 1.31 [0.94, 1.82]


Total events 79 62
Heterogeneity: tau2 = 0.07; chi2 = 10.63, df = 5 (p = 0.06); I2 = 53%
Test for overall effect: Z = 1.57 (p = 0.12) 0.01 0.1 1 10 100
Favours [experimental] Favours [control]

Figure 11: Forest plot for responder rate (acupuncture vs medication).

Acupuncture Medication Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Jin, 2010 6.95 2.46 22 10.7 3.2 15 17.5 –1.32 [–2.05, –0.59]
Peng, 2013 8.08 3.769 63 9.31 4.759 29 20.7 –0.30 [–0.74, 0.14]
Shi, 2017 7.23 3.9 30 5.73 3.15 30 20.0 0.42 [–0.09, 0.93]
Wang, 2010 5.15 2.32 48 9.42 2.7 24 19.3 –1.72 [–2.29, –1.15]
Wu, 2014 (2) 8.25 2.18 228 9 2.04 115 22.5 –0.35 [–0.58, –0.12]

Total (95% CI) 391 213 100.0 –0.62 [–1.23, –0.01]


Heterogeneity: tau2 = 0.42; chi2 = 36.90, df = 4 (p < 0.00001); I2 = 89%
Test for overall effect: Z = 1.99 (p = 0.05) –4 –2 0 2 4
Acupuncture Medication

Figure 12: Forest plot for CSS (acupuncture vs medication).

Experimental Control Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
Dai, 2016 63.7 7.73 30 65.8 9.81 30 11.7 –0.23 [–0.74, 0.27]
Liu, 2016 (2) 19.3 6.21 30 28.7 8.67 30 10.9 –1.23 [–1.79, –0.68]
Mao, 2017 45.4 10.1 30 50.9 10.8 32 11.7 –0.52 [–1.03, –0.01]
Ou, 2012 12.6 13.2 84 20.5 18.9 86 15.1 –0.48 [–0.79, –0.18]
Song, 2016 61.1 11.9 20 73.8 12.2 19 9.2 –1.03 [–1.71, –0.36]
Wang, 2013 0.73 0.55 37 0.91 0.44 17 10.6 –0.34 [–0.92, 0.24]
Wang, 2016 (2) 39.7 10.7 19 69.5 17.1 19 7.7 –2.05 [–2.85, –1.25]
Xu, 2015 0.85 0.52 30 1.18 0.63 30 11.6 –0.56 [–1.08, –0.05]
Zhou, 2013 58.4 19.8 30 72.8 20.7 30 11.5 –0.70 [–1.22, –0.18]

Total (95% CI) 310 293 100.0 –0.73 [–1.02, –0.44]


Heterogeneity: tau2 = 0.12; chi2 = 22.36, df = 8 (p = 0.004); I2 = 64%
Test for overall effect: Z = 4.89 (p < 0.00001) –4 –2 0 2 4
Favours [experimental] Favours [control]

Figure 13: Forest plot for PAC-QOL (acupuncture vs medication).


Evidence-Based Complementary and Alternative Medicine 11

Acupuncture Medication Weight Risk ratio Risk ratio


Study or subgroup
Events Total Events Total (%) M-H, fixed, 95% CI M-H, fixed, 95% CI
Chen, 2019 0 30 4 31 9.4 0.11 [0.01, 2.04]
Mao, 2017 2 30 2 32 4.1 1.07 [0.16, 7.10]
Ou, 2012 0 84 0 86 Not estimable
Peng, 2013 2 63 1 29 2.9 0.92 [0.09, 9.75]
Shi, 2017 0 30 9 30 20.3 0.05 [0.00, 0.87]
Wang, 2010 0 48 0 24 Not estimable
Wu, 2014 (3) 1 79 3 25 9.7 0.11 [0.01, 0.97]
Wu, 2014 (2) 6 228 10 115 28.3 0.30 [0.11, 0.81]
Wu, 2017 0 123 4 67 12.4 0.06 [0.00, 1.11]
Xu, 2015 5 30 6 30 12.8 0.83 [0.28, 2.44]

Total (95% CI) 745 469 100.0 0.30 [0.18, 0.52]


Total events 16 39
Heterogeneity: chi2 = 9.94, df = 7 (p = 0.19); I2 = 30%
0.001 0.1 1 10 1000
Test for overall effect: Z = 4.33 (p < 0.0001)
Medication Acupuncture

Figure 14: Forest plot for safety evaluation (acupuncture vs medication).

Acupuncture Medication Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
2.1.1. vs prucalopride
Dai, 2016 1.92 0.88 30 1.62 0.63 30 15.1 0.30 [–0.09, 0.69]
Mao, 2017 (2) 2.63 0.53 20 2.56 0.48 20 16.0 0.07 [–0.24, 0.38]
Song, 2016 2.73 0.18 20 2.27 0.24 19 17.8 0.46 [0.33, 0.59]
Wang, 2016 (2) 2.69 2.04 19 2.31 2.01 19 5.4 0.38 [–0.91, 1.67]
Wang, 2017 2.21 0.89 30 1.98 1.09 30 13.4 0.23 [–0.27, 0.73]
Subtotal (95% CI) 119 118 67.8 0.32 [0.14, 0.50]
Heterogeneity: tau2 = 0.01; chi2 = 5.64, df = 4 (p = 0.23); I2 = 29%
Test for overall effect: Z = 3.53 (p = 0.0004)
2.1.2. vs mosapride
Wang, 2016 3.89 0.86 34 2.36 0.39 34 16.0 1.53 [1.21, 1.85]
Subtotal (95% CI) 34 34 16.0 1.53 [1.21, 1.85]
Heterogeneity: not applicable
Test for overall effect: Z = 9.45 (p < 0.00001)

2.1.3. vs lactulose
Liu, 2016 (2) 1.58 0.66 30 1.02 0.49 30 16.3 0.56 [0.27, 0.85]
Subtotal (95% CI) 30 30 16.3 0.56 [0.27, 0.85]
Heterogeneity: not applicable
Test for overall effect: Z = 3.73 (p = 0.0002)
Total (95% CI) 183 182 100.0 0.53 [0.17, 0.88]
Heterogeneity: tau2 = 0.18; chi2 = 50.22, df = 6 (p < 0.00001); I2 = 88%
Test for overall effect: Z = 2.88 (p = 0.004) –4 –2 0 2 4
Test for subgroup differences: chi2 = 42.31, df = 2 (p < 0.00001); I2 = 95.3% Medication Acupuncture

Figure 15: Forest plot for CSBM by subgroup analysis.

categorical variable, may have differentially influenced the cardiac arrest [61, 62]. Therefore, to avoid the effect of
heterogeneity. However, most of the results of the included different mechanisms of action and side effects of drugs on
high-quality studies did not include categorical variable data, the results, we added a different subgroup analysis based on
and we cannot judge whether the two analysis methods have drug control.
different effects on the results. Compared with the first-line agents, the subgroup
The current study included five Western medicines that analysis showed that acupuncture may be more effective
were directly compared with acupuncture, including saline than lactulose in increasing weekly CSBMs and more ad-
laxatives (polyethylene glycol), osmotic laxatives (lactulose), vantageous than polyethylene glycol, prucalopride, and
and 5-HT agonists (prucalopride, mosapride, and cisapride). lactulose in improving the quality of life. It was suggested
The guidelines have different mechanisms of action and side that acupuncture caused fewer adverse events than poly-
effects, such as mosapride, which only acts in the upper ethylene glycol and lactulose. However, the evidence is
digestive tract, and cisapride, which is associated with insufficient because of the drug characteristics, small sample
12 Evidence-Based Complementary and Alternative Medicine

Acupuncture Medication Weight Mean difference Mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
2.2.1. vs prucalopride
Dai, 2016 3.18 0.68 30 2.99 0.32 30 10.6 0.19 [–0.08, 0.46]
Mao, 2017 (2) 3.4 0.75 20 4.9 1.02 20 9.6 –1.50 [–2.05, –0.95]
Song, 2016 4.61 0.97 20 3.13 1.03 19 9.3 1.48 [0.85, 2.11]
Wang, 2016 (2) 3.22 0.48 19 3.37 0.83 19 10.1 –0.15 [–0.58, 0.28]
Wang, 2017 3.43 0.65 30 4.85 1.02 30 10.1 –1.42 [–1.85, –0.99]
Subtotal (95% CI) 119 118 49.7 –0.29 [–1.19, 0.62]
Heterogeneity: tau2 = 1.00; chi2 = 87.09, df = 4 (p < 0.00001); I2 = 95%
Test for overall effect: Z = 0.62 (p = 0.53)

2.2.2. vs mosapride
Ding, 2017 4.08 1.26 33 3.11 1.15 30 9.5 0.97 [0.37, 1.57]
Lian, 2014 3.97 0.64 33 3.23 0.8 30 10.3 0.74 [0.38, 1.10]
Xu, 2015 3.44 0.9 30 3.26 0.97 30 9.9 0.18 [–0.29, 0.65]
Subtotal (95% CI) 96 90 29.7 0.62 [0.19, 1.05]
Heterogeneity: tau2 = 0.09; chi2 = 5.07, df = 2 (p = 0.08); I2 = 61%
Test for overall effect: Z = 2.80 (p = 0.005)

2.2.3. vs lactulose
Ruan, 2018 2.43 0.5 21 1.88 0.61 24 10.4 0.55 [0.23, 0.87]
Shi, 2017 4.27 0.58 30 3.53 0.97 30 10.2 0.74 [0.34, 1.14]
Subtotal (95% CI) 51 54 20.6 0.62 [0.37, 0.88]
Heterogeneity: tau2 = 0.00; chi2 = 0.52, df = 1 (p = 0.47); I2 = 0%
Test for overall effect: Z = 4.84 (p < 0.00001)
Total (95% CI) 266 262 100.0 0.17 [–0.33, 0.68]
Heterogeneity: tau2 = 0.62; chi2 = 134.74, df = 9 (p < 0.00001); I2 = 93%
Test for overall effect: Z = 0.67 (p = 0.50) –2 –1 0 1 2
Test for subgroup differences: chi2 = 3.68, df = 2 (p = 0.16), I2 = 45.7% Medication Acupuncture

Figure 16: Forest plot for BSFS by subgroup analysis.

Acupuncture Medication Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
2.3.1. vs lactulose
Jin, 2010 6.95 2.46 22 10.7 3.2 15 17.5 –1.32 [–2.05, –0.59]
Peng, 2013 8.08 3.769 63 9.31 4.759 29 20.7 –0.30 [–0.74, –0.14]
Shi, 2017 7.23 3.9 30 5.73 3.15 30 20.0 0.42 [–0.09, 0.93]
Wang, 2010 5.15 2.32 48 9.42 2.7 24 19.3 –1.72 [–2.29, –1.15]
Wu, 2014 (2) 8.25 2.18 228 9 2.04 115 22.5 –0.35 [–0.58, –0.12]
Subtotal (95% CI) 391 213 100.0 –0.62 [–1.23, –0.01]
Heterogeneity: tau2 = 0.42; chi2 = 36.90, df = 4 (p < 0.00001); I2 = 89%
Test for overall effect: Z = 1.99 (p = 0.05)
Total (95% CI) 391 213 100.0 –0.62 [–1.23, –0.01]
Heterogeneity: tau2 = 0.42; chi2 = 36.90, df = 4 (p < 0.00001); I2 = 89%
Test for overall effect: Z = 1.99 (p = 0.05) –2 –1 0 1 2
Test for subgroup differences: not applicable Acupuncture Medication

Figure 17: Forest plot for CSS by subgroup analysis.

size, and inadequate blinding. Studies showed that poly- 4.2. Strengths. This meta-analysis has several strengths.
ethylene glycol and lactulose were not effective in alleviating Compared with previous reviews and meta-analyses, the
abdominal pain and bloating, which directly affect the unified specifications of the FC diagnostic criteria for in-
quality of life of patients [62]. Because of the inert char- clusion in this review were all Rome III, except for one RCT
acteristics of acupuncture, it is difficult to implement a [44]. We included several high-quality multicenter RCTs
blinded method when choosing medication as a control. with large sample sizes from 2010 to 2019, including the
Therefore, the effectiveness of acupuncture is impossible to largest trial with 1075 patients, which pinpointed that EA
exclude because the patient has greater expectations for reduced the scores of constipation symptoms and quality of
acupuncture treatment, especially improvements in sub- life in patients with chronic severe functional constipation
jective feelings. after 8 weeks [28]. This review observed more
Evidence-Based Complementary and Alternative Medicine 13

Acupuncture Medication Weight Std. mean difference Std. mean difference


Study or subgroup
Mean SD Total Mean SD Total (%) IV, random, 95% CI IV, random, 95% CI
2.4.1. vs polyethylene glycol
Mao, 2017 45.4 10.1 30 50.9 10.8 32 11.7 –0.52 [–1.03, –0.01]
Ou, 2012 12.6 13.2 84 20.5 18.9 86 15.1 –0.48 [–0.79, –0.18]
Subtotal (95% CI) 114 118 26.8 –0.49 [–0.75, –0.23]
Heterogeneity: tau2 = 0.00; chi2 = 0.02, df = 1 (p = 0.90); I2 = 0%
Test for overall effect: Z = 3.68 (p = 0.0002)

2.4.2. vs prucalopride
Dai, 2016 63.7 7.73 30 65.8 9.81 30 11.7 –0.23 [–0.74, 0.27]
Song, 2016 61.1 11.9 20 73.8 12.2 19 9.2 –1.03 [–1.71, –0.36]
Wang, 2016 (2) 39.7 10.7 19 69.5 17.1 19 7.7 –2.05 [–2.85, –1.25]
Subtotal (95% CI) 69 68 28.6 –1.07 [–2.08, –0.05]
Heterogeneity: tau2 = 0.69; chi2 = 14.49, df = 2 (p = 0.0007); I2 = 86%
Test for overall effect: Z = 2.06 (p = 0.04)

2.4.3. vs mosapride
Wang, 2013 0.73 0.55 37 0.91 0.44 17 10.6 –0.34 [–0.92, 0.24]
Xu, 2015 0.85 0.52 30 1.18 0.63 30 11.6 –0.56 [–1.08, –0.05]
Subtotal (95% CI) 67 47 22.1 –0.47 [–0.85, –0.08]
Heterogeneity: tau2 = 0.00; chi2 = 0.31, df = 1 (p = 0.57); I2 = 0%
Test for overall effect: Z = 2.37 (p = 0.02)

2.4.4. vs lactulose
Liu, 2016 (2) 19.3 6.21 30 28.7 8.67 30 10.9 –1.23 [–1.79, –0.68]
Subtotal (95% CI) 30 30 10.9 –1.23 [–1.79, –0.68]
Heterogeneity: not applicable
Test for overall effect: Z = 4.35 (p < 0.0001)

2.4.5. vs cisapride
Zhou, 2013 58.4 19.8 30 72.8 20.7 30 11.5 –0.70 [–1.22, –0.18]
Subtotal (95% CI) 30 30 11.5 –0.70 [–1.22, –0.18]
Heterogeneity: not applicable
Test for overall effect: Z = 2.63 (p = 0.008)
Total (95% CI) 310 293 100.0 –0.73 [–1.02, –0.44]
Heterogeneity: tau2 = 0.12; chi2 = 22.36, df = 8 (p = 0.004); I2 = 64%
Test for overall effect: Z = 4.89 (p < 0.00001) –4 –2 0 2 4
Test for subgroup differences: chi2 = 7.03, df = 4 (p = 0.13), I2 = 43.1% Acupuncture Medication

Figure 18: Forest plot for PAC-QOL by subgroup analysis.

comprehensive outcome indicators related to the effec- There are still some unanswered questions. First, the
tiveness of FC treatment involving the frequency and optimal variables deserve further investigation, including
symptoms of defecation, stool form, quality of life, and side acupuncture type, frequency, duration, and selection of
effects and compared acupuncture with other clinical drugs acupoints in acupuncture treatment. Our literature review
for FC to show the effectiveness and safety of acupuncture found that many other types of acupuncture are used to
more intuitively. treat FC, including warm needles, acupoint injections, and
ear needles. No research showed that acupuncture or EA
was the best method to treat FC, which requires further
4.3. Limitations and Implications for Research and Practice. research.
There are some limitations in this study. First, blinding Second, recent studies investigated the effectiveness of
remains a common challenge in acupuncture clinical re- acupuncture for chronic severe FC, but there was no
search, and 19 RCTs had a high risk in the blinding of comprehensive data analysis to determine the efficacy of
participants and personnel in our risk of bias assessment. acupuncture for chronic severe FC. There remain further
Future trials should strengthen the effectiveness of the unanswered questions about which patients may find acu-
blinding method and adopt appropriate fake devices to puncture most beneficial in terms of FC severity. We know
examine research questions, minimize potential bias, and that patients generally experience a range of other symptoms
improve the quality of the evidence. Second, most RCTs during constipation, such as anxiety, abdominal pain, and
were performed in China, which may lead to publication anorexia. Traditional acupuncturists consider these symp-
bias and affect the validity and reliability of this systematic toms when making treatment plans. More trials of this type
review. Databases in other languages should be considered are needed to model real-world settings.
for inclusion in the future, such as Japanese, Korean, and Finally, our subgroup analysis results showed that
German. comparisons of acupuncture and drugs revealed many
14 Evidence-Based Complementary and Alternative Medicine

Acupuncture Medication Weight Risk ratio Risk ratio


Study or subgroup
Mean Total Mean Total (%) M-H, random, 95% CI M-H, random, 95% CI
2.5.1. vs prucalopride
Dai, 2016 10 30 8 30 12.5 1.25 [0.57, 2.73]
Mao, 2017 (2) 6 20 5 20 8.5 1.20 [0.44, 3.30]
Song, 2016 8 20 2 19 4.8 3.80 [0.92, 15.67]
Wang, 2016 (2) 8 19 6 19 11.1 1.33 [0.57, 3.11]
Subtotal (95% CI) 89 88 36.9 1.43 [0.89, 2.29]
Total events 32 21
Heterogeneity: tau2 = 0.00; chi2 = 2.14, df = 3 (p = 0.54); I2 = 0%
Test for overall effect: Z = 1.49 (p = 0.14)

2.5.2. vs mosapride
Xu, 2015 29 30 27 30 37.0 1.07 [0.94, 1.23]
Subtotal (95% CI) 30 30 37.0 1.07 [0.94, 1.23]
Total events 29 27
Heterogeneity: not applicable
Test for overall effect: Z = 1.03 (p = 0.31)

2.5.3. vs lactulose
Ruan, 2018 18 21 14 24 26.0 1.47 [1.00, 2.15]
Subtotal (95% CI) 21 24 26.0 1.47 [1.00, 2.15]
Total events 18 14
Heterogeneity: not applicable
Test for overall effect: Z = 1.98 (p = 0.05)

Total (95% CI) 140 142 100.0 1.31 [0.94, 1.82]


Total events 79 62
Heterogeneity: tau2 = 0.07; chi2 = 10.63, df = 5 (p = 0.06); I2 = 53%
Test for overall effect: Z = 1.57 (p = 0.12) 0.005 0.01 1 10 200
Test for subgroup differences: chi2 = 3.32, df = 2 (p = 0.19), I2 = 39.7% Medication Acupuncture

Figure 19: Forest plot for responder rate by subgroup analysis.

Acupuncture Medication Weight Risk ratio Risk ratio


Study or subgroup
Events Total Events Total (%) M-H, fixed, 95% CI M-H, fixed, 95% CI
2.6.1. vs polyethylene glycol
Chen, 2019 0 30 4 31 9.4 0.11 [0.01, 2.04]
Mao, 2017 2 30 2 32 4.1 1.07 [0.16, 7.10]
Ou, 2012 0 84 0 86 Not estimable
Subtotal (95% CI) 144 149 13.6 0.40 [0.10, 1.67]
Total events 2 6
Heterogeneity: chi2 = 1.74, df = 1 (p = 0.19); I2 = 43%
Test for overall effect: Z = 1.25 (p = 0.21)

2.6.2. vs mosapride
Wu, 2014 (3) 1 79 3 25 9.7 0.11 [0.01, 0.97]
Wu, 2017 0 123 4 67 12.4 0.06 [0.00, 1.11]
Xu, 2015 5 30 6 30 12.8 0.83 [0.28, 2.44]
Subtotal (95% CI) 232 122 34.9 0.36 [0.16, 0.80]
Total events 6 13
Heterogeneity: chi2 = 4.98, df = 2 (p = 0.08); I2 = 60%
Test for overall effect: Z = 2.49 (p = 0.01)

2.6.3. vs lactulose
Peng, 2013 2 63 1 29 2.9 0.92 [0.09, 9.75]
Shi, 2017 0 30 9 30 20.3 0.05 [0.00, 0.87]
Wang, 2010 0 48 0 24 Not estimable
Wu, 2014 (2) 6 228 10 115 28.3 0.30 [0.11, 0.81]
Subtotal (95% CI) 369 198 51.5 0.24 [0.10, 0.56]
Total events 8 20
Heterogeneity: chi2 = 2.59, df = 2 (p = 0.27); I2 = 23%
Test for overall effect: Z = 3.33 (p = 0.0009)

Total (95% CI) 745 469 100.0 0.30 [0.18, 0.52]


Total events 16 39
Heterogeneity: chi2 = 9.94, df = 7 (p = 0.19); I2 = 30%
Test for overall effect: Z = 4.33 (p < 0.0001) 0.001 0.1 1 10 1000
Test for subgroup differences: chi2 = 0.61, df = 2 (p = 0.74), I2 =0% Medication Acupuncture

Figure 20: Forest plot for safety evaluation by subgroup analysis.


Evidence-Based Complementary and Alternative Medicine 15

Table 3: GRADE evaluation: acupuncture compared to sham acupuncture.


No. of MD or
Other
Condition participants Design Limitations Inconsistency Indirectness Imprecision SMD or RR Quality
considerations
(studies) (95% CI)
0.84 (0.65
CSBM 1171 (3) RCT No serious Serious No serious No serious Reporting bias Low
to 1.03)
0.24 (0.15
BSFS 1224 (3) RCT No serious Serious No serious No serious Reporting bias Low
to 0.34)
−0.42
CSS 432 (4) RCT Serious Serious Serious Serious Reporting bias (−0.81 to Very low
−0.02)
−0.33
PAC-QOL 1075 (1) RCT No serious No serious No serious No serious Reporting bias (−0.45 to Moderate
−0.21)
Responder 2.16 (1.1 to
1262 (3) RCT No serious Serious No serious No serious Reporting bias Low
rate 4.24)
Safety 1.21 (0.78
1627 (7) RCT Serious No serious No serious No serious None Moderate
evaluation to 1.87)
RCT, randomized controlled trial; MD, mean difference; SMD, standard mean difference; RR, relative risk; CI, confidence interval.

uncertainties in outcome indicators. The most prominent Chengdu University of Traditional Chinese Medicine Xin-
requirement in the past was to perform more high-quality glin Scholars Program (no.YXRC2018007).
RCTs to evaluate the effectiveness of acupuncture for the
treatment of FC. This meta-analysis suggested that acu- Supplementary Materials
puncture was better than some clinical medicines in in-
creasing defecation frequency and quality of life. Therefore, S1: checklist of items to include when reporting a systematic
more trials are needed in the future to clarify the clinical review or meta-analysis. (Supplementary Materials)
advantages and disadvantages of acupuncture and explore
how acupuncture can supplement or replace the shortage of
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