Systematic Review And Meta-Analysis Of Acupuncture Therapy As An Intervention For Migraine

ObjectiveFollowing the basis of evidence-based medicine,the objective of this study is to evaluate the quality of randomized controlled trials using acupuncture as an intervention method for the treatment of migraine in accordance with the guidelines of the CONSORT(Consolidated Standards of Reporting Trials)statement-STRICTA(Standards for Reporting Interventions in Clinical Trials of Acupuncture)checklist.Subsequently,the acupuncture points used in all included studies were extracted and analysed.Using bivariate analysis,a heatmap showing the combination and occurrence of all acupuncture points were shown and used to create a proposed acupuncture protocol for the treatment of migraine.A meta-analysis was performed to determine the statistical effect of the efficacy of acupuncture therapy in the treatment of migraine.Lastly,various summary of findings table will be presented to migraineurs and clnicians alike to show the different grades of recommendation for acupuncture therapy.This study was conducted in order to improve the service quality and clinical skills of acupuncturists in Singapore.MethodsClinical trials for this study was mainly retrieved through electronic databases.Databases searched will include Chinese databases and English databases.Chinese databases included in the search are China National Knowledge Infrastructure(CNKI),China Biomedical Literature Data(CBM),VIP Database(VIP),and Wanfang Medical Network.English databases included are PubMed,ScienceDirect,Embase and the Cochrane Library.All randomized controlled trials published before December 2018 will be included.Hand searching through the citations of included studies was also performed.The search parameters for studies is stated below are("acupuncture"[MeSH Terms]OR "acupuncture"[All Fields]OR"acupuncture therapy"[MeSH Terms]OR("acupuncture"[All Fields]AND"therapy"[All Fields])OR"acupuncture therapy"[All Fields])OR needling[All Fields]AND("migraine disorders"[MeSH Terms]OR("migraine"[All Fields]AND "disorders"[All Fields])OR "migraine disorders"[All Fields]OR "migraine"[All Fields])?Study inclusion criteria:1.Study design:Clinical studies or clinical trials are randomized controlled trials(RCT)or semi-randomized controlled trials;subjects must be randomly assigned.The abstract or main text of the study should contain terms such as "randomized control","randomized allocation","randomized" and such,Blinding of whichever party is not required.2.Population:Patients who were clinically diagnosed with migraine were eligible for inclusion regardless of any migraine subtypes.The clinical diagnosis should be based on the diagnostic criteria established in ICHD-1,ICHD-2,ICHD-3,the Guiding Principles for Clinical Research of New Drugs in Traditional Chinese Medicine,or the Expert Consensus for Diagnosis and Prevention of Migraine.Age,gender,race,and nationality are not restricted.3.Intervention:The treatment group must receive acupuncture therapy as the main intervention method.4.Control:The control group can receive traditional Chinese medication,modern medication,acupuncture therapy,sham acupuncture or other forms of therapy.However,control group therapy cannot be absent.5.Outcome:The main outcome indicator for this study is the number of clinically successful cases of migraineurs after treatment;the secondary outcome indicators are the long-term and short term efficacy of acupuncture therapy,the rate of migraine attacks after treatment,the total headache time experienced post treatment,changes in concentrations of certain plasma substances,changes in TCD scans of migraineurs post treatment and number of migraineurs who experienced adverse effects during treatment.6.Full text or accurate data must be accessible.Exclusion criteria:1.Non-randomized controlled trials or observational studies.2.Crossover studies.3.Animal trials or laboratory studies.4.Non-clinical studies such as systematic reviews,meta-analysis,discussions,and summary of clinical experience.5.Comparative study of migraineurs and non-migraineurs.6.Repeated publications in different databases.7.Non-Chinese and English literature.8.Clinical studies that cannot be traced.9.Clinical trials that are ongoing or possess incomplete data.10.Interventions that do not feature acupuncture therapy as the main intervention method.Data extraction:Studies chosen from electronic databases were kept and managed using Endnote x7.The data extracted from the studies after screening include the author' s name(s),year of publication,randomization method,blinding of parties,migraine subtypes,number of subjects,number of treatment and control groups,comparison of sample sizes between groups,intervention method,efficacy indicators,selection of acupuncture points,effectiveness of the two groups,invalid cases of the two groups,statistical processing methods,author conclusions.All extracted data is entered and managed via Microsoft Excel 2013.All meta-analysis charts were created using Revman 5.3.Literature screening:In the first phase,two evaluators independently screened selected clinical studies.Screening through the title,abstract and keywords of the study in accordance to the inclusion and exclusion criterias,an initial number of studies were collected.In the second stage,after reading through the full text of the literature and applying the same filters from the inclusion and exclusion criterias,a final number of clinical studies to be included in this study was collected.When two evaluators had differences during the screening stage,a third evaluator was engaged to give the final judgment in the inclusion or exclusion of a specific literature.Literature quality evaluation:The final conclusions of systematic reviews and meta-analysis are closely related to the quality of the included literature.If the quality of the included literature is not subject to rigorous quality assessment,the results presented by the meta-analysis and subsequent discussions no longer be accurate and degrades the clinical guidance value of a systematic review and meta-analysis.Included studies were evaluated according to the CONSORT-STRICTA checklist to determine their qualityAssessing the risk of bias:Risk of bias was evaluated in accordance to the risk of bias tool developed by the Cochrane collaboration.A total of 7 areas will be assessed:1.The method of randomization.2.Allocation concealment.3.Blinding of participants.4.Blinding of those performing the intervention method.5.Integrity of outcome.6.Risk of selective reporting of outcome.7.Other bias.Analysis of acupuncture points:All acupuncture points used in the included studies were listed and analyzed,the results displayed using a heatmap.An occurrence analysis was also performed to determine commonly paired acupuncture points.Publication bias:Using Revman 5.3,a funnel plot was created to assess the publication bias within included studies.Meta-analysis:Meta-analysis of the included literature was performed using Revman 5.3 software.Test of heterogeneity and sensitivity analysis was performed to stabilize the results of the meta-analysis.Test of heterogeneity:Heterogeneity occurs naturally due to factors such as different experimental designs or different outcome indicators.Subgroup analysis and sensitivity analysis were performed in the presence of high heterogeneity to explore the source of heterogeneity and to provide explanation for it.Subgroup analysis:Subgroup analysis of different control groups and outcome measures were performed to further remove heterogeneity and to determine the best performing area of acupuncture therapy.ResultsA total of 23 articles were included after screening.CONSORT-STRICTA checklist revealed that included studies were lacking in the reporting of randomization methods,blinding protocols,allocation concealment,disclosure of possible adverse reactions,limitations of the study and clinician qualifications.The risk of bias tool shows that most of the included literature contains unknown risks.After analysis of acupuncture points used in the included studies,a prescription of acupuncture points for migraine was proposed as followed.Main points:Fengchi,Taiyang,Taichong,Shuaigu,Baihui;auxiliary points:phlegm and dampness syndrome,Fenglong;liver qi stagnation syndrome and liver yang disruption syndrome,Taichong;qi and blood deficiency syndrome,plus Zusanli,Sanyinjiao;blood stasis syndrome,plus Geshu.This combination of acupuncture points is based on the experience and results of predecessors.This proposed prescription can also improve the clinical effectiveness of acupuncture treatment for migraine.There is a small amount of publication bias among studies that are included in the meta-analysis.Clinical studies with large sample sizes are published more frequently,while clinical studies with small sample sizes are published less.Asymmetry in the funnel plot illustrates the presence of reporting bias in the included literature.Outcome data in studies with small sample size was especially biased toward the intervention group,to the point of exceeding the 95%CI.Since most included studies failed to report blinding protocols and allocation concealment,an asymmetrical distribution can be seen on the funnel plot.Meta-analysis of the proved that the clinical effectiveness of acupuncture therapy was superior compared to the control group,but due to the presence of moderate heterogeneity between included literatures,subgroup analyses were subsequently performed based on different control groups and secondary outcome measures.Acupuncture therapy is shown to perform better compared to f lunarizine,ergotamine-caf feine,nimodipine and carbamazepine.Acupuncture therapy was shown to be able to achieve a clinical effectiveness similar to sumatriptan.Two clinical studies have chosen to compare needle manipulation techniques or unconventional acupuncture points on with conventional acupuncture as a control.There is no heterogeneity between the documents.The outcome data indicated that the combination of needle manipulation techniques or certain unconventional points can significantly improve the clinical efficiency of acupuncture therapy.Subgroup analysis of acupuncture versus sham acupuncture shows acupuncture therapy to be statistically superior.The sham acupuncture points,although located close to the acupuncture points selected in the intervention group still failed to achieve the same clinical effectiveness.This illustrates the specificity of acupuncture points in the human body,and also serves as a reminder for acupuncturists to pay-attention to the accuracy of acupuncture points while performing acupuncture.In terms of long-term efficacy and short-term efficacy,acupuncture has significant advantages in the treatment of migraine compared to control groups.In terms of reducing the frequency of migraine attacks and the headache duration,although the data supports the effect of acupuncture therapy,lack of standardized measurement protocols for both outcomes affected the credibility of the results by-introducing high heterogeneity between studies.Acupuncture has been found to maybe affect the concentration of plasma endothelin(ET)and nitric oxide(NO)in migraineurs,opening up a new path for future researchers to explore.Transcranial Doppler(TCD)test was used to observe the changes of migraineurs before and after treatment.Acupuncture treatment may relieve intracranial vasospasm,reduce blood flow velocity and thereby relieve the symptoms of migraine,but the evidence is not statistically significant.The number of adverse reactions in acupuncture was significantly less than in other control interventions.Finally,according to the results of the GRADE profiling,clinicians can strongly recommend acupuncture therapy to migraineurs who are currently taking ergotamine-caffeine or nimodipine.Acupuncture therapy can be recommended for migraineurs who are currently taking sumatriptan as a treatment plan with less adverse reactions.For migraineurs currently taking flunarizine or carbamazepine,current clinical research evidence does not fully support acupuncture as an alternative to medication,but it can be suggested as a treatment method with less adverse reactions.ConclusionThe systematic review and meta-analysis results of this study show that acupuncture therapy has a positive effect in the treatment of migraine.After analyzing and proposing a prescription for the treatment of migraine,it can be concluded that the acupuncture points on the gallbladder meridian and the liver meridian can improve the symptoms of migraine,possessing clinical effectiveness that is superior when compared to modern medicine.This could be caused by the change in plasma endothelin and nitric oxide concentration in migraineurs post treatment,and it is worthy to be explored in future researches.Finally,the currently published randomized controlled trials using acupuncture therapy as an intervention method for migraine are mostly of medium quality.Future researchers need to further improve the study design method and reporting quality in order to produce higher quality literature to better judge the authenticity of the results.