Effectiveness and safety of moxibustion for primary insomnia

14 Pages·2016·1.76 MB·English

Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217
DOI10.1186/s12906-016-1179-9
RESEARCH ARTICLE Open Access
Effectiveness and safety of moxibustion for
primary insomnia: a systematic review and
meta-analysis
Yu-Jiao Sun1, Jia-Min Yuan2 and Zhi-Min Yang2*
Abstract
Background: Primary insomniais a widespread and refractory disease. Moxibustion therapyfor insomnia shows
some advantages compared with conventional therapies. This systematic review and meta-analysis of randomized
controlled trials (RCTs) was conducted to evaluate the effectiveness and safety of moxibustion therapy for insomnia.
Methods: We conducted a comprehensive literature review of the CENTRAL, PubMed, EMBASE, Webof science,
CNKI, VIP,and Wanfang Data databases from their inception to July 2015 for RCTs that compared moxibustion with
western medications, oral Chinese medicine, or othermethodsof traditional Chinese medicine (TCM) in patients
withprimaryinsomnia. The primary outcome measure was effective rate and secondary outcome measure was
adverse events. Data collection and analysis included risk of bias evaluation, meta-analysis,sensitivity analysis,
publication bias and adverse events analysis according to corresponding criteria.
Results: The study included 22 RCTs (1,971patients). The quality ofthe studies was low. The overall meta-analysis
demonstrated that moxibustionwas more effective for insomnia than western medications, oral Chinese medicine
andotherTCMtherapies(RR=1.17,95%CI1.12to1.23,P<0.00001).Subgroupanalysesdemonstratedthatmoxibustion
wasmoreeffectiveforinsomniathanwesternmedications(RR=1.16,95%CI1.09to1.24,P<0.00001),oralChinese
medicine(RR=1.11,95%CI1.04to1.18,P=0.002),andotherTCMtherapies(RR=1.22,95%CI1.15to1.30,P<0.
00001).Therewerenoseriousadverseeffectsassociatedwithmoxibustiontherapyforinsomnia,andtherateofadverse
eventswaslow.
Conclusion:It is difficult to get the conclusion regarding the effectiveness and safety of moxibustion for primary
insomnia due to insufficient evidence, such as the high risk of bias in the included studies, small sample sizes,
and few reports on adverse effects. Moxibustion should be considered as a novel therapeutic option for
insomnia, and more rigorous clinical trials of moxibustion therapy for insomnia are needed to assess its effects.
Keywords: Moxibustion, Insomnia, Systematic Review
Background thought to be associated with a group of centrally lo-
Descriptionofthecondition cated neurons coupled with dynamic transformation of
Insomnia is a sleep disorder characterized by the inability neurotransmitters, including norepinephrine (NE) and
to fall asleep, sleep loss and poor-quality sleep. Insomnia 5-hydroxytryptamine (5-HT) [5].
iscausedbymultiplephysiological,psychological,anden- In industrialized countries, insomnia is an epidemic
vironmentalfactors[1–4]. [6–9], where an estimated 40 % of the population suffers
Insomniaisrelatedtothefunctionofthecerebralcortex from the disorder [10–16]. An international survey pub-
and results from mental or nervous tension. Insomnia is lished in 2008 estimated the prevalence of insomnia at
23 % in Japan, 31 % in Western Europe, and 56 % in the
UnitedStates[17].
*Correspondence:[email protected]
Insomnia can lead to memory problems, depression
2GuangdongHospitalofTraditionalChineseMedicine,No.111,DadeRoad,
YueXiuDistrict,Guangzhou,Guangdong510120,China [18–20], irritability, and an increased risk for cardio-
Fulllistofauthorinformationisavailableattheendofthearticle
©2016TheAuthor(s).OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.0
InternationalLicense(http://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinkto
theCreativeCommonslicense,andindicateifchangesweremade.TheCreativeCommonsPublicDomainDedicationwaiver
(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.
Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page2of14
cerebrovascular diseases [21–23], such as headache [24], diseases by improving the blood supply to brain tissue,
hypertension [25–27], and heart failure [28]. Insomnia increasing the elasticity of blood vessels, and enhancing
can decreasean individual’s health-related quality of life the excitability of related sites on the cerebral cortex
[29], leading to functional impairment while awake [54]. In TCM, moxibustion is thought to regulate qi and
[29–31] and consequences such as automobile-related the blood, tonifying healthy qi to eliminate pathogenesis
accidents [32] and absenteeism [33–37]. by means of warming. Moxibustion applied at Bǎihuì can
However, insomnia remains under-diagnosed and balanceyinandyang,tonifyboththeheartandthespleen,
under-treated. An estimated 47-67 % of individuals dredgebloodvessels,andtranquilize[54]mind[5].
with insomnia do not seek medical attention. Among
those that do attempt to resolve their sleep problems, Whyitisimportanttodothisstudy
only 50–90 % receive treatment [17, 38]. The effectiveness of moxibustion therapy for insomnia
remains controversial; therefore, its application is lim-
Descriptionoftheintervention ited.Therearecurrentlynopublishedsystematicreviews
Western conventional medicine recommends pharmaco- or meta-analyses investigating the effectiveness and
logical treatment (such as hypnotic sedative agents) and safety ofmoxibustion therapyfor insomnia.
cognitivebehavioral therapy (CBT)forinsomnia[39].
Pharmacological agents are effective for insomnia but Objective
are only recommended for short-term relief. The long- This systematic review and meta-analysis of randomized
term use of these medications is associated with adverse controlled trials (RCTs) was conducted as a rigorous
effects such as disturbed sleep architecture, rebound evaluation of the effectiveness and safety of moxibustion
insomnia, withdrawal effects [40], damage to cerebral therapyfor insomnia.
nerves, memory and psychomotor impairment, hypo-
function, dependency, and addiction [41]. For example, Methods
benzodiazepines may cause headaches, nightmares, This systematic review and meta-analysis is reported ac-
daytime fatigue, nausea, confusion, and falls [42]. Z- cording to the Preferred Reporting Items for Systematic
drugs can result in bizarre behaviors, dizziness, falls, ReviewsandMeta-Analyses(PRISMA) guidelines[55].
and gastrointestinal upset [43].
Evidencefrom clinical studies supports the useof CBT Databaseandsearchstrategy
for insomnia [44, 45]. However, CBT is not effective Two review authors (SYJ and YJM) independently
in all patients [46], and access to treatment is limited searched the Cochrane Central Register of Controlled
[45, 47] because qualified CBT therapists are rare Trials (CENTRAL), PubMed, EMBASE, Web of Science,
[48] and expensive [49]. Chinese National Knowledge Infrastructure (CNKI),VIP
Consequently, insomnia sufferers require alternative information database, and Wanfang Data Information
treatments[50, 51].Moxibustion isacomponent usedin Site from their inception to July 2015. Searches were re-
traditional Chinese medicine (TCM). Some Chinese strictedtostudiesintheEnglishandChineselanguages.
studies by randomized controlled trials (RCTs) or clin- Medline(Pubmed)searchstrategy:
ical observations suggest that the moxibustion has the
potential to be an effective and safe therapy for insom- 1. insomniaORdyssomniaOR sleep OR sleep disorder
nia,such asimproving sleep quality, adjusting thebrain’s OR sleep maintenanceOR somnipathy(infulltext);
sleep function, improving symptoms of dreaminess, diz- 2. moxibustionORmoxa(infulltext);
ziness, headache, heavy head and poor memory, and 3. clinical trialORcontrolled clinicaltrialOR
promotingtheperiodicityfrom light todeepsleep [52]. randomizedcontrolled trialORrandomizedclinical
trial(infulltext);
Howtheinterventionmightwork 4. #1AND #2 AND#3
Modern medicine believes moxibustion modulates neu-
rotransmitters to resist insomnia, thereby improving A monthly e-mail alert was set up at the National
sleep quantity [53]. Experiments in rats indicate that Center for Biotechnology Information (NCBI) from the
moxibustion protects against chronic stress by acting on U.S. National Library of Medicine (NLM) to obtain up-
the hippocampal neurons to increase the amount of dates ofnewpublications.
brain-derived neurotrophic factor as well as 5-HT and
its metabolites. Holistic healthcare uses moxibustion to Inclusioncriteria
generate far-infrared and near infrared energy to regu-
late dysfunctional organs and build wellbeing [54]. Sus- 1) RCTsofpatientsthatweredissatisfiedwith their
pended moxibustion at Baihui can treat nervous system qualityofsleep;
Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page3of14
2) inwhich theintervention groupincludedpatients 3) trialsinspecialpatientpopulationssuchas
undergoingtherapywith differentmethods of menopausalwomen;
moxibustionasmonotherapy orcombination 4) trialsinwhich moxibustionascombinationtherapy
therapy(including grain-moxibustion,thunder-fire wasnotthe onlyintervention todiffer between the
moxibustion,heat-sensitivemoxibustion),and the treatmentand control group;
controlgroupincludedpatientsundergoingtherapy 5) studies reporting fraudulentdata orwith insufficient
with western medications,or oralChinesemedicine, data;
orotherTCMtherapies(includingacupointmassage, 6) duplicate studies.
point-application,head-needleacupuncture,auricular-
plastertherapy,andacupuncture); Studyselection
3) Theprimaryoutcomemeasure wasthe clinical Two review authors (SYJ, YJM) independently examined
effective rate.Itwasadichotomousoutcome and titles and abstracts to select eligible RCTs. When data-
theoveralleffectivenessofmoxibustiontherapyasa sets overlapped or were duplicated, only the most recent
subjectiveassessment,whichwasdefinedasthe information was included. Then the full text of poten-
proportionofparticipantswhogotimprovedinsleep tially relevant studies was retrieved. Two author re-
qualityandwasbasedonresponseevaluationcriteria viewers (SYJ and YJM) independently examined the full
usedinthetreatmentofinsomniawithTCM.What’s text records to determine which studies met the inclu-
more,itwasreportedbytrialparticipantsthemselves. sion criteria. Disagreements about the study selection
Forexample,clinicaltherapeutic effectcriteriawas were resolved by discussion with a third review author
categorizedascure,markedlyeffective, effective,or (YZM) andconsensus.
ineffective.accordingtothe Guideline forClinical
Trials ofNewPatent Chinesemedicines Dataextractionandmanagement
(GCTNPCM)evaluation standards,which define: (1) Two review authors (SYJ and YJM) independently ex-
clinical cureassleep timetorestore normalsleep tracted the data from eligible RCTs including details on
timeORanighttime sleep duration of<6h,deep the study population, interventions, and outcome mea-
sleep, andfullofenergyafterwakingup;(2) sures. Disagreements about data extraction were re-
markedly effectiveassignificant improvementof solved through discussion with a third review author
insomnia,sleep timeincreased<3hcompared to (YZM) andconsensus.
previoussleep time andan increaseinthedepth of
sleep; (3)effective asameliorationinsymptomsas Assessmentofqualityofevidenceinincludedstudies
sleep timeincreased<3hcompared withthe The methodological quality of RCTs was assessed inde-
previoussleep time;and (4)ineffective asno pendently using the Cochrane Handbook for Systematic
significantimprovement ofinsomniaOR Reviews of Interventions [57] from 7 parts, including
deteriorated aftertreatment [39,56].Thenthe random sequence generation, allocation concealment,
patientsof“cure,markedlyeffective, effective”were blinding of participants and personnel, blinding of out-
taken aspeoplewhogotimprovedinsleep quality come assessments, incomplete outcome data, selective
and thepatientsof“ineffective”weretaken aspeople reporting,andotherbias.
whogotunimprovedinsleep quality.Thetotal Two review authors (SYJ, YJM) independently evalu-
numberof“cure,markedlyeffective, effective”were ated the methodological quality of the included articles.
used tocalculate effective rate. Disagreements about the assessment of quality of evi-
Otherassessmentcriteriaofclinicaltherapeuticeffect dence in included studies were resolved through discus-
withcomparabledefinitionswerealsoconsidered[39]. sionwith athird review author (YZM) andconsensus.
4) Thesecondaryoutcomemeasurewasadverseevents RCTs with fraudulent data of low quality were not in-
associatedwiththeuseofmoxibustiontherapyfor cluded inthe meta-analysis.
insomnia.Itwasreportedinthearticlesormeasured
byvalidatedscales,e.g.,HealthSurveyQuestionnaire, Data analysis
TreatmentEmergentSymptomScale(TESS)etal. Statistical analyses were performed using Review Man-
5) OnlyEnglish andChineseaslanguageselection ager [Computer program] Version 5.3. (RevMan5.3,
Copenhagen: The Nordic Cochrane Centre, The
Exclusioncriteria Cochrane Collaboration, 2014). Risk ratios (RRs) with
95%CIswere calculatedfor dichotomousvariables.
1) studies thatwerenotRCTs; A random-effects model was used to pool the studies
2) patientsdiagnosedwithprimaryinsomniaresulting with significant heterogeneity, as determined by the in-
from another physiologicalor psychologicaldisease; consistency index (I2≥30 %). A fixed effect model was
Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page4of14
used to pool the studies in the absence of substantial vs. western medications: range, 10 [54] to 30 days [59];
heterogeneity (I2<30%). moxibustion vs. oral Chinese medicine: range, 10 [68] to
Sensitivity analyses were conducted to explore the im- 32 days [63]; moxibustion vs. other TCM therapies:
pact ofconfounding factors. range,10[72]to47days [73]).
Publication bias was comprehensively assessed using In the control groups of the 22 included trials, the
funnel plot by RevMan v5.3. and Begg’s rank correlation treatment methods included 2 western medications (Es-
test of asymmetry by stata.13.0. Publication bias was tazolam [54, 59, 60, 62], Diazepam plus Oryzanol plus
thoughttobeinsignificantatP>0.05 [58]. V [61]), 6 oral Chinese medicine therapies (Sanhuang
B1
Anshen decoction [65], Renshenguipi pill [66], Huatan-
Results jieyu decoction [68], Tianwangbuxin decoction [63],
Trialidentification Anshen Bunao decoction [67], Anshen Bunao Ye [64]),
The searches identified 590 articles. Titles and abstracts and 5 other TCM therapies (head-acupoint massage [75,
were screened, and 77 RCTs were considered potentially 77], point-application [76], head-needle acupuncture
eligible forinclusion. Afteranalyzingthe full-text articles [78], auricular-plaster therapy [71, 73], and acupuncture
and a risk of bias assessment, 55 RCTs were excluded. [5, 69, 70, 72, 74]). The treatment duration of the con-
Twenty-two RCTs were found eligible based on our in- trol groups ranged from 7 [68] to 47 days [73]: (moxi-
clusion criteria (Fig.1). bustion vs. western medications: range, 10 [54] to
30 days [59]; moxibustion vs. oral Chinese medicine:
Characteristicsofincludedstudies range, 7 [68] to 30 days [64, 65]; moxibustion vs. other
The characteristics of the 22 included trials (n=1,971) TCMtherapies:range,10[72]to47days [73]).
were summarized in Table 1. Five trials [54, 59–62] The effectiveness of moxibustion was classified ac-
compared moxibustion with western medications (n= cording to 5 criteria: (1) GCTNPCM [5, 60–63, 66, 67,
477; moxibustion: n=241, control: n=236) (Table 1a), 70, 72, 74, 75, 77], (2) CDT&ETCMD&S [65], (3) PSQI
six trials [63–68] compared moxibustion with oral [64], (4) WHO sleep efficiency calculation [54, 69, 78],
Chinese medicine (n=533; moxibustion: n=267, con- (5)unclearcriteria [59,68,71,73,76].
trol: n=266) (Table 1b), and eleven trials [5, 69–78] The baseline was comparable because there were no
compared moxibustion with other TCM therapies (n= significant differences in gender, age, or disease duration
961; moxibustion: n=491, control: n=470) (Table 1c). betweentheintervention andcontrol groups (P>0.05).
Patients included in the 22 trials were 13 [60] -
75 years [59, 67] of age (moxibustion vs. western medi- Riskofbiasinincludedstudies
cations: range, 13 [60] - 75 years [59]; moxibustion vs. Theoverallriskof biasinthe22includedtrialswashigh
oralChinesemedicine:range,18[66]-75years[67];moxi- (Fig. 2).
bustion vs. other TCM therapies: range, 18 [71, 78] - In 10trials [5,60–62,65, 70,72,75,77,78],therisk of
72years[71]).Theoveralldurationofdiseaseinthe22in- bias due to random sequence generation was assessed as
cluded trials ranged from 1 week [67] to 30 years [59] low because a random number table was used. In 12 tri-
(moxibustionvs.westernmedications:range,1month[60] als [54, 59, 63, 64, 66–69, 71, 73, 74, 76], the risk of bias
to 30 years [59]; moxibustion vs. oral Chinese medicine: due to random sequence generation was assessed as un-
range, 1 week [67] to 16 years [64]; moxibustion vs. other clear duetoinsufficientdetailsinthereport.
TCMtherapies:range,1month[70]to20years[73]). In all 22trials [5,54,59–78], therisk of biasdue to al-
The diagnostic criteria used in the 22 trials included location concealment was assessed as unclear due to in-
(1) Chinese classification and criteria for mental disor- sufficientdetails inthereport.
ders 3rd edition (CCMD-3) [5, 60–62, 65–69, 71, 73, 77], In all 22 trials [5, 54, 59–78], the risk of bias due to
(2) Chinese classification and diagnostic criteria for blinding of participants and personnel was assessed as
mental disorders second edition-revision (CCMD-2-R) high. Blinding of participants and personnel was never
[72, 74], (3) GCTNPCM [63, 66, 75], (4) International possible because all the included trials adopted conven-
Classification of Disease 10th Version (ICD-10) [60, 61, tional western medications, oral Chinese herbal medi-
63, 70, 71], (5) sleep efficiency calculation of the World cine, or other TCM interventions such as massage, or
HealthOrganization(WHO)[54],(6)CriteriaofDiagno- acupuncture.
sis and Therapeutic Effects for TCM Disease and Syn- In all 22 trials [5, 54, 59–78], the risk of bias due
drome (CDT&ETCMD&S) [59, 65, 67, 72, 78], (7) to blinding of outcome assessments was assessed as
Pittsburgh Sleep Quality Index (PSQI) [64], and (8) un- high because the primary outcome (effective rate)
clear criteria [76]. was reported by trial participants only according to
The treatment duration of the treatment groups inclusion criteria and trial participants were never
rangedfrom 10 [54, 68, 72] to 47 days [73] (moxibustion possible to be blinded.
Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page5of14
Fig.1Flowchartofliteraturesearch.Followingthesearchstrategy,590articleswereidentifiedfrommedicalliteraturedatabases,and77required
furtherassessment.Finally,22articleswereincludedinthisreview
In 19 trials [5, 54, 59–64, 67–72, 74–78], the risk of treat (ITT) analysis, though the dropouts were less than
bias due to incomplete outcome data was assessed as 20%ineach article.
low because there were no missing data and all expected Inall22trials[5,54,59–78],theriskof biasduetose-
outcomes were reported. Three articles [65, 66, 73] were lective reporting was assessed as low because all the tri-
assessed as having unclear risk because they did not re- als reported all of the outcomes that they had specified
port sufficient detail to let usmakesurethe baseline was in their methods and no additional outcomes were
balanced after dropouts and did not use an intention-to- reported.
Table1Characteristicsoftrialsincludedinthemeta-analysis S
u
n
a.Moxibustionvs.Westernmedications e
t
a
Includedtrials Eligibilitycriteria Interventionsandtreatmentduration Sampleandcharacteristics(malefemale,age, OutcomeCriteria(effective l.
diseaseduration) rateCriteria) BM
C
Trial Control Trial Control C
o
m
Wu2014[59] CD&TETCMD&S Moxibustion Estazolam 91; 91; Unclear p
Duration:30d Duration:30d AGE:20-75; AGE:20-75; lem
Diseaseduration:3m-30y Diseaseduration:3m-30y; en
ta
Wong2014[62] CCMD-3 Moxibustion Estazolam 40(M:18,F:22); 40(M:16;F:24); GCTNPCM ry
Duration:20d Duration:20d AGE:18-63(mean:38); AGE:18-66(mean:39); a
n
Diseaseduration:1.5m-4y Diseaseduration:1.2m-6y d
A
Yu -CCMD-3 Moxibustion Estazolam 30; 30; GCTNPCM lte
rn
2012[60] -ICD10 Duration:21d Duration:14d AGE:13-65; AGE:13-65; a
Diseaseduration:1m-8y Diseaseduration:1m-8y; tiv
e
M
Ju Sleepefficiency Moxibustion Estazolam 40(M:18,F:22); 35(M:14F:21); Sleepefficiencycomputation e
d
2009[54] computation Duration:10d Duration:10d AGE:25-75; AGE:25-75; ic
Diseaseduration:0.5y-5y Diseaseduration:0.5y-5y ine
Yuan2007[61] -CCMD-3 Moxibustion -Diazepam 40; 40; GCTNPCM (20
-ICD10 Duration:20d -Oryzanol AGE14-65; AGE14-65; 16
–VB1 Diseaseduration:1m-10y; Diseaseduration:1m-10y; ) 16
Duration:20d :2
1
7
b.Moxibustionvs.oralChinesemedicine
Includedtrials Eligibilitycriteria Interventionsandtreatmentduration Sampleandcharacteristics(malefemale,age, OutcomeCriteria(effective
diseaseduration) rateCriteria)
Trial Control Trial Control
Jiao2015[65] -CCMD-3 -Moxibustion-SanhuangAnshen SanhuangAnshen 80(M:37,F:43); 79(M:-,F:-); CDT&ETCMD&S
-CDT&ETCMD&S DecoctionDuration:30d Decoction AGE:(mean:67.8); AGE:(mean:65.1);
Duration:30d Diseaseduration:-; Diseaseduration:-;
Liu2015[66] -CCMD-3 Grain-moxibustion Renshenguipipill 38; 38; GCTNPCM
-GCTNPCM Duration:14d Duration:14d AGE:18-70; AGE:18-70;
Diseaseduration:-; Diseaseduration:-;
Zhang2014[68] -CCMD-3 -Moxibustion Huatanjieyu 59; 59; Unclear
-Huatanjieyudecoction decoction AGE:34-65; AGE:34-65;
Duration:10d Duration:7d Diseaseduration:-; Diseaseduration:-;
He2014[63] -ICD-10- -Moxibustion-Tianwangbuxin Tianwangbuxin 30(M:12,F:18); 30(M:13,F:17); GCTNPCM
-GCTNPCM decoction decoction AGE:30-60 AGE:31-60
Duration:32d Duration:28d (mean:45.3±4.4); (mean:46.2±5.1);
Diseaseduration:-; Diseaseduration:-;
Wu2010[67] -CCMD-3 -Heat-sensitiveMoxibustion– AnshenBunao 30(M:13,F:17); 30(M:11,F:19); GCTNPCM
-CDT&ETCMD&S AnshenBunaodecoction decoction AGE:33-74(mean:46.8); AGE:35-75(mean:45.7);
Duration:22d Duration:22d Diseaseduration:1w-2.7y Diseaseduration:1w-2.5y P
a
g
Hu PSQI Moxibustion AnshenBunaoYe 30(M:12,F:18); 30(M:14,F:16); PSQI e
6
2007[64] Duration:30d Duration:30d AGE:19-65; AGE:18-67; o
Diseaseduration:24d-16y Diseaseduration:20d-14y f1
4
Table1Characteristicsoftrialsincludedinthemeta-analysis(Continued) S
u
n
c.Moxibustionvs.otherTCMtherapies et
a
Includedtrials Eligibilitycriteria Interventionsandtreatmentduration Sampleandcharacteristics(malefemale,age, OutcomeCriteria(effective l.
B
diseaseduration) ratecriteria) M
C
Trial Control Trial Control Co
m
Xie2015[77] CCMD-3 -Moxibustion Head-acupoint 30(M:17,F:13); 30(M:14,F:16); GCTNPCM ple
-Head-acupointmassage massage AGE: AGE:(mean:42.7±12.4y); m
e
Duration:28d Duration:28d (mean:43.3±13.8y); Diseaseduration:(mean: n
Diseaseduration:(mean: 10.8±4.7m); tary
11.5±5.3m); a
n
d
Wang2014[76] Unclear -Moxibustion Point-application 18(M:10,F:8); 18(M:11,F:7); Unclear A
-Point-application Duration:15d AGE:39-65y(mean:45.2y); AGE:41-69y(mean:48.1y); lte
Duration:15d Diseaseduration:- Diseaseduration:- rna
Xu2014[78] CD&TETCMD&S -Heat-sensitiveMoxibustion Head-needle 58(M:-,F:-); 54(M:-,F:-); sleepefficiencyby tive
-Head-needleacupuncture acupuncture AGE:18-70y; AGE:18-70y; internationalstandard M
e
Duration:24d Duration:24d Diseaseduration:12m-60m Diseaseduration:12m- dic
60m in
e
Shu2014[75] GCTNPCM -Moxibustion Head-acupoint 9(M:0,F:9); 9(M:0,F:9); GCTNPCM (2
0
-Head-acupointmassage massage AGE:30-56; AGE:30-56; 1
6
Duration:15d Duration:15d Diseaseduration:2m-7m Diseaseduration:2m-7m ) 1
6
Ma2014[73] CCMD-3 -Moxibustion Auricular-plaster 99(M:38,F:61); 96(M:33,F:63); unclear :2
1
-Auricular-plastertherapy therapy AGE:20-64y AGE:21-62y 7
Duration:47d Duration:47d (mean:38±13y); (mean:37±12y);
Diseaseduration:0.5y-20y Diseaseduration:0.5y-20y
(mean:7.48±4.57y) (mean:7.13±4.92y)
Li2014[70] ICD-10 -Moxibustion -Acupuncture 35(M:12,F:23); 35(M:8,F:27); GCTNPCM
-Acupuncture Duration:21d AGE:20-60y AGE:25-60(mean:48±4.
Duration:21d (mean:45±3.5y); 9y);
Diseaseduration:1m-18m Diseaseduration:1m-
(mean:5.5±4.2m) 18m
(mean:5.6±0.4m)
Quan2012[74] CCMD-2-R -Moxibustion Acupuncture 36(M:15,F:21); 36(M:17,F:19); GCTNPCM
-Acupuncture Duration:43d AGE:19-67y AGE:20-68y
Duration:43d (mean:38.9y); (mean:40.6y);
Diseaseduration:6m-9y Diseaseduration:5m-10y
(mean:5.3y); (mean:5y);
Ao2011[69] CCMD-3 -Moxibustion Acupuncture 34(M:13,F:21); 33(M:14,F:19); Sleepefficiencyby
-Acupuncture Duration:32-33d AGE:(mean:40.54±11.27); AGE:(mean:39.67±11.93); internationalstandard
Duration:32-33d Diseaseduration:(mean:9.7± Diseaseduration:(mean:
2.45m); 8.47±1.69m);
Li2011[5] CCMD-3 -Moxibustion Acupuncture 100(M:46,F:54); 98(M:45,F:53); GCTNPCM
-Acupuncture Duration:28d AGE: AGE:(mean:36.67±10.93);
Duration:28d (mean:35.58±9.87); Diseaseduration:(mean: P
a
Diseaseduration:(mean:21.59 22.76±8.39m); ge
±7.87m); 7
o
f
Chen2010[71] -CCMD-3 -Moxibustion 37(M:-,F:-); 26(M:-,F:-); Unclear 1
4
Table1Characteristicsoftrialsincludedinthemeta-analysis(Continued) S
u
n
-ICD-10 -Auricular-plastertherapy Auricular-plaster AGE:18-72(mean:48); AGE:18-72(mean:48); e
t
Duration:22-23d therapy Diseaseduration:2m-7y Diseaseduration:2m-7y a
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Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page9of14
In 19 trials [5, 54, 59–64, 67–72, 74–78], the risk of
bias due to other reasons was assessed as low because
these studies appeared to be free of other sources of
bias. Three articles [65, 66, 73] were assessed as being at
unclear risk because there were no sufficient detail to let
usmakesurethebaselinewasbalancedafterdropouts.
Effectiverateofmoxibustionforinsomnia
The effective rate of moxibustion for insomnia was de-
scribedinall22includedtrials.
The overall meta-analysis (Fig. 3) demonstrated that
moxibustion was more effective for insomnia than west-
ern medications, oral Chinese medicine and other TCM
therapies (RR=1.17, 95 % CI 1.12 to 1.23, P < 0.00001).
There was an evidence of significant heterogeneity be-
tween the trials (χ2=33.46, P=0.04, I2=37 %) and tests
for subgroup differences showed there were somepoten-
tial differences between the groups (χ2=4.37, P=0.11,
I2=54.3 %).
The subgroup meta-analysis (Fig. 3) demonstrated that
moxibustion was more effective for insomnia than west-
ern medications [54, 59–62] (RR=1.16, 95 % CI 1.09 to
1.24, P<0.00001), oral Chinese medicine [63–68] (RR=
1.11, 95 % CI 1.04 to 1.18, P = 0.002), and other TCM
therapies [5, 69–78] (RR=1.22, 95 % CI 1.15 to 1.30,
P<0.00001). There were no evidence of significant
heterogeneity between the trials comparing moxibus-
tion vs. western medications [54, 59–62] (χ2=2.14, P=
0.71, I2=0 %) and moxibustion vs. other TCM therapies
[5, 69–78] (χ2=9.11, P=0.52, I2=0 %). But there was an
evidence of significant heterogeneity between the trials
comparing moxibustion vs. oral Chinese medicine
[63–68] (χ2=7.53, P=0.18, I2=34 %).
To account for clinical heterogeneity and subgroup
differences probably arising from the use of different cri-
teria toevaluate theeffectiveness ofmoxibustion therapy
for insomnia, a sensitivity analysis of trials using only
GCTNPCM criteria was conducted. The effectiveness of
moxibustion classified according to GCTNPCM criteria
was described in 12 trials (moxibustion vs. western med-
ications in 3 trials [60–62], moxibustion vs. oral Chinese
medicine in 3 trials [63, 66, 67] and moxibustion vs.
otherTCMtherapiesin6trials[5,70,72,74,75,77]).
In sensitivity analysis (Fig. 4), the overall meta-analysis
demonstrated that moxibustion was significantly more
effective for insomnia than western medications, oral
Chinese medicine and other TCM therapies (RR=1.21,
95 % CI 1.14 to 1.28, P<0.00001). There was no evi-
dence of significant heterogeneity between the trials
(χ2=3.15, P=0.99, I2=0 %) and tests for subgroup dif-
ferences showed there were no potential differences be-
Fig.2Riskofbiasinincludedstudies tween the groups (χ2=1.14, P=0.57, I2=0 %).
In sensitivity analysis (Fig. 4), the subgroup meta-
analysis demonstrated that moxibustion was still more
Sunetal.BMCComplementaryandAlternativeMedicine (2016) 16:217 Page10of14
Fig.3Forestplotandmeta-analysisofeffectiverate
Fig.4Forestplotandmeta-analysisofeffectiverateforsensitivity