Efficacy of Transcranial Magnetic Stimulation for Reducing ...

The results showed that TMS was also significantly effective in alleviating depression. In summary, our survey of the existing research ... ThisarticleispartoftheResearchTopic NeuralBasesofNeurologicalandPsychiatricDisordersandTheirNeuromodulationTreatments Viewall 34 Articles Articles HongmingLi UniversityofPennsylvania,UnitedStates MohamedA.Abdelnaim FacultyofMedicine,UniversityofRegensburg,Germany MelanieL.Bozzay WarrenAlpertMedicalSchoolofBrownUniversity,UnitedStates Theeditorandreviewers'affiliationsarethelatestprovidedontheirLoopresearchprofilesandmaynotreflecttheirsituationatthetimeofreview. Abstract Introduction Methods Results Discussion DataAvailabilityStatement AuthorContributions Funding ConflictofInterest Publisher'sNote SupplementaryMaterial References SuggestaResearchTopic> DownloadArticle DownloadPDF ReadCube EPUB XML(NLM) Supplementary Material Exportcitation EndNote ReferenceManager SimpleTEXTfile BibTex totalviews ViewArticleImpact SuggestaResearchTopic> SHAREON OpenSupplementalData SYSTEMATICREVIEWarticle Front.Psychiatry,18January2022 |https://doi.org/10.3389/fpsyt.2021.764183 EfficacyofTranscranialMagneticStimulationforReducingSuicidalIdeationinDepression:AMeta-Analysis YananCui1,HaijianFang1,CuiBao2,WanyueGeng2,FengqiongYu3*andXiaomingLi3* 1SchoolofMentalHealthandPsychologicalSciences,AnhuiMedicalUniversity,Hefei,China 2SchooloftheFirstCollegeforClinicalMedicine,AnhuiMedicalUniversity,Hefei,China 3AnhuiProvinceKeyLaboratoryofCognitionandNeuropsychiatricDisorders,DepartmentofMentalHealthandPsychologicalScience,TheSecondAffiliatedHospitalofAnhuiMedicalUniversity,AnhuiMedicalUniversity,Hefei,China Objectives:Thisstudyaimedtosystematicallyreviewtheefficacyoftranscranialmagneticstimulationtreatmentinreducingsuicidalideationindepression. Methods:PubMed,WebofScience,CBMdisc,WanFang,ChongqingVIP,andCNKIdatabaseswereelectronicallysearchedforrandomizedcontrolledtrialsoftranscranialmagneticstimulation(TMS)interventioninthemanagementofsuicidalideationfrominceptiontoFebruary24,2021.Tworeviewersindependentlyscreenedstudies,extracteddata,andassessedthequalityofincludedstudies.Meta-analysiswasthenperformedusingSTATA15.1software. Results:Atotalofeightarticlesinvolving566patientswereincluded.Themeta-analysisresultsshowedthatthesuicidalideationscoresofthegroupwhoreceivedTMStreatmentweresignificantlylower[standardizedmeandifference(SMD)=−0.415,95%confidenceinterval(CI):−0.741to−0.090,P=0.012]thanthoseofthecontrolgroup.Subgroupanalysisshowedthatage,TMSpattern,frequencyofintervention,andstimulationthresholdalteredtheTMSefficacy. Conclusions:EvidenceshowedthatTMSachievedsuperiorresultsinreducingsuicidalideation.Becauseofthelimitedqualityandquantityoftheincludedstudies,morehigh-qualitystudiesarerequiredtoverifytheconclusions. SystematicReviewRegistration:https://inplasy.com/,identifier:INPLASY202180065. Introduction Majordepressivedisorder(MDD)isaserious,worldwidementalissue,influencingmillionsofindividuals(1).Morethan50%ofChinesepatientswithMDDhavesuicidalideation(2).Suicideisnotonlyamajorhealthproblembutalsoasocialproblem(3).AccordingtoglobaldatareleasedbytheWorldHealthOrganizationin2012,morethan800,000peoplediebysuicideeveryyear,accountingfor1.4%oftheworld'sdeathtollandmakingitthe15thleadingcauseofdeath(4,5).Thelifetimeprevalenceofsuicideideationisapproximately9.2%onaglobalscale(6).Suicidalideationisdefinedasthinkingabout,considering,orplanningsuicide(6).InareviewoftheECTinterventionliterature,Finketal.foundthatECTwaseffectiveforindividualswithmajordepressionandsuicide,andforfollow-up(7).Ciprianietal.foundthattheLiinterventiongroupreducedsuicidedeathsbyatleast60%comparedtothecontrolgroup(8).Accessiblepsychologicalandpharmacologicalinterventionshavemeantthatadvancementshavebeenmadeinreducingsuicide(9);however,thesearenotwithoutsideeffects,whichinfluencestheireffectivenessandmayfurthernegativelyaffectthosealreadyathighriskofsuicide(10).Henceinventivetreatmentprocedurestopreventsuicide,forusealongsideexistingtreatments,arefundamentallyrequired. Thereisagrowinginterestintheuseofnon-invasivebrainincitementtechniquestodecreasesuicidalintentandbehavior.Transcranialmagneticstimulation(TMS)isanon-invasivemagneticstimulationtechnologyinwhichapulsedmagneticfieldactsonthecentralnervoussystem(mainlythebrain)tochangethemembranepotentialofcorticalnervecellstoproduceinducedcurrent,whichaffectsbrainmetabolismandnerveelectricalactivity,andcausesaseriesofphysiologicalandbiochemicalreactions(11).AformofTMS,intermittentTBS(iTBS),actuatesalong-termpotentiation(LTP)-likeimpactbyexpandingthepostsynapticconcentrationofcalciumparticles(12).BothTBSandtraditionalpatternedTMScaninduceplasticchangesinaparameter-dependentmanner(e.g.,inhibitorexciteasafunctionoffrequency).Thephysiologicalandtherapeuticantidepressantmagnitudeoftheeffectseemtobesimilar.PhysiologicalstudieshaveshownthatthedurationofthephysiologicalmodulationonthemotorcortexmaybelongerforTBSthanpatternedTMS.Itisnotclearthatthistranslatestoclinicalefficacythough(infact,theantidepressantbenefitsmaybeshorter)(13–16).TBShasbeenshowntobesafeandwell-tolerated,andtohaveantidepressantproperties(17).Arecentstudy(18)suggeststhatTBSisefficaciousinsuicide. OtherstudieshavediscussedthatrTMScanaffecttheemotionalandcognitivestateofpatients(19),andthatpatientswithsuicidalideationandbehavioroftenhavedamagetoareasofthebrainthatareinvolvedincognitiveandemotionalcontrolfunctions(20,21),andthatthetargetsofTMShappentobeimplicatedinthesebrainareas(22),whichlendssupporttotheideathatTMSwouldbeexpectedtobeaneffectivetreatmentforsuicideanditspotentialuseasatreatmentforsuicidalideation. Somestudies(23)havenotdemonstratedasignificantdifferenceinthereductionofsuicidescoresbetweenactiveTMSstimulationandshamstimulation.Bycomparingtheeffectsofepilepsytreatmentandnon-invasivebrainstimulationonsuicide,Chenetal.supportedtheeffectofECTonacutesuicidalideation,buttheycouldnotsuggestthesameforMST,rTMS,ortDCS(24).Bozzayetal.review(25)supportstheongoinguseofTMSasanewmediumtoreducesuiciderisk;Serafinietal.analyzedtherelationshipbetweenrTMSinterventionsandsuicidalbehavior,oneofmultiplesuicidaldimensions(e.g.,suicidalideation,intensityofsuicidalthoughts,suicidalbehavior,andsuicidalintent),inasystematicstudy(26).AMeta-analysis(27)concludedthattheefficacyandefficiencyofhighfrequencywashigherthanthatoftheshamstimulationgroup;Brunonietal.(28)includednearly100studiesandshowedthatlowfrequencystimulationwasthemosteffective,whilehighfrequencystimulationwastheleasteffective,bilateralstimulationwasintermediate,andbilateralstimulationandlowfrequencystimulationwerethemostacceptableofthestimulationmodes;Dell'Ossoetal.(29)showedthathigh-frequencystimulationandlow-frequencystimulationweresimilarlyeffective.Thetreatmentisalsoeffectiveinspecialpopulations,especiallyadolescents,butthefollow-upanddelayedeffectsofthetreatmentarealsoofconcerninadolescentswhoarenotfullyneurologicallymature.However,fewmeta-analysessupporttheuseofTMSforsuicidalideation(oneofmultiplesuicidaldimensions)interventionsorprovideinsightintohowbesttodevelopandutilizesuchinterventions.Tofillthisknowledgegap,weconductedameta-analysisontheefficacyofTMSinthetreatmentofsuicidalideation,withsubgroupanalysesofTMSpatterns,age,stimulationfrequencyandintensity. Methods ThestudyhasbeenregisteredonINPLASYwebsite.Theregistrationnumberofthismeta-analysesprotocolisINPLASY202180065. SearchStrategy Sixelectronicdatabasesweresearchedforrelevantstudies:PubMed,WebofScience,WanFang,ChineseNationalKnowledgeInfrastructure,ChongqingVIP,andCBMdisc,fromtheirestablishmenttoFebruary24,2021,withnorestrictionsonthepublicationyear.Theword“suicide”wascombinedwith“transcranialmagneticstimulation”andthesearchstrategyofcombiningsubjectwordswithfreewordswasadopted(SupplementaryMaterials).Studieswereassessedbytheinclusionandexclusioncriteriabelowandsortedfirstbyexaminationoftitle,thenabstract,thenthefulltext.Thefinalsearchofeachdatabasewasperformedindependentlyandseparatelybytworeviewers. InclusionCriteria Theselectedstudieswerethosethatmetthefollowingeligibilitycriteria:(1)randomizedcontrolledtrialspublishedinEnglishorChinese;(2)theageofparticipantsrangedfrom13-to80-years-old;(3)thestudygroupwastreatedwithTMSoraphysicalinterventionwithadefinitetreatmentplan,includingadifferentsequenceandfrequencyofneurophysicalstimulation;(4)thecontrolgrouphadnorestrictionsinthetreatmenttheyreceived(exceptotherphysicaltreatmentssuchasECT,TDCS,etc.),includingconventionaltreatment,placebotreatment,andwaitingfortreatment;and(5)theevaluationresultswereofsuicidalideationandsuicidalbehavior. DataExtraction Informationwasextractedindependentlybytworeviewersinastandardizedmanner.Anydisagreementswerediscussedwithanotherreviewer,toreachconsensus.EngaugeDigitizer12.1wasusedtoobtainmoreinformation[Onlyonestudy(30)intheincludedstudiesdidnotgivethedataweneeded,butweextractedthemfromthefigurebymeansofthetool].Thefollowingdatawereextractedforeachstudy:firstauthor'sname,yearofpublication,location,samplesize,psychometricinstrumentsandmeanandstandarddeviationofsuicideideationscore.Wealsoextractedinformationonsamplesize,age,typeofTMS,interventionfrequency,andintensitythreshold,inordertoestimateTMSefficacyforsuicidalideationbysubgroups. QualityAssessment Cochraneriskofbiasassessment(31)wasusedtoevaluatethestudyqualityaccordingtothefollowingcriteria:randomsequencegeneration,allocationconcealment,blinding,incompleteoutcomedata,selectivereporting,andothersourcesofbias.Eachareawasrankedforhigh,low,orunknownbiasrisk.WealsocalculatedtheJadadscoreforeachoftheincludedstudies(32).IncalculatingtheJadadscore,eachstudywasevaluatedaccordingtothequalityofrandomization,blindingprocedures,anddescriptionofwithdrawalsanddropouts.Jadadscoresrangedfrom0to5,withtrialsscoring3orgreaterconsideredgoodqualitytrials. StatisticalAnalysis WPSOffice3.0.2softwarewasusedtoorganizetheincorporatedliteratureanddata,andstatisticalanalysiswascompletedusingSTATAversion15.1software.TheQtestwasusedtoexplorethevariationbetweenstudies.TheI2statisticreflectedtheproportionofheterogeneityinthetotalvariationofeffect.IftheheterogeneitytestresultswereP>0.1andI2<50%,thehomogeneityoftheincludedstudieswasconsideredtobegood,andafixedeffectsmodelwasused;otherwise,arandomeffectsmodelwasused.PublicationbiaswasassessedbyafunnelplotandEgger'stest.SubgroupanalysiswasconductedtoexplorethepotentialheterogeneitybetweenstudiesandtheefficacyofTMSinterventionforsuicidalideationaccordingtodifferentcharacteristics. Results CharacteristicsofEligibleStudies Throughsearching,145potentiallyrelatedarticleswerefound.Afterthetitleandabstractwerescreened,aremaining29documentswerescreenedforfulltext.Finally,eightarticlesmettheinclusioncriteriaformeta-analysis.Twostudieswithinonearticlemettheinclusioncriteria,makingatotalofninestudiesformeta-analysis.ThedocumentscreeningprocessandresultsareshowninFigure1. FIGURE1 Figure1.PRISMAflowdiagramofthesystematicreviewphases. ThebaselineinformationfromtheincludedstudiesispresentedinTable1.Ninesham-controlledclinicaltrials,includingatotalof566patients,7rTMS-controlledclinicaltrialincludingatotalof490patients,2iTBS-controlledclinicaltrialincludingatotalof76patientswereincludedinthepresentsystematicreview.Clinicalsamplesincludedpredominantlypatientswithsuicidalideationandoneofthefollowingpsychiatricdiagnoses:MDD,treatmentresistantdepression(TRD).Subjectsinallstudiesweretakingantidepressantsduringtreatment,exceptforStefanieetal.Chrisetal.(Onlyhabitualbenzodiazepineagentswereallowed),twostudieswentthroughadrugwashoutperiod.Thecontrolgroupinallstudieswasgivenashamstimulationtreatment,i.e.,thesamecoilalsoemitsatappingsoundonthesurfaceofthepatient'sscalp,butwithoutpulses.TheJadadscoreforalltheincludedstudieswas≥3.TheresultsofthebiasriskassessmentareshowninTable2. TABLE1 Table1.Characteristicsofeligiblestudiesincludedinthemeta-analysis. TABLE2 Table2.Qualityassessmentofincludedstudies. OverallEfficacyofTMS SuicidalIdeation TheefficacyofTMSinterventionforreducingsuicidalideationwascalculatedforeachstudy,asshowninFigure2.Theresultsofthemeta-analysisshowedthatthesuicidalideationscoresofthegroupwhoreceivedTMStreatmentforsuicidalideationwerestatisticallysignificantlylower[standardizedmeandifference(SMD)=−0.415,95%confidenceinterval(CI):−0.741to−0.090,P=0.012]thanthoseofthecontrolgroup.Theheterogeneityofthestudieswashigh[heterogeneitychi-squared(χ2)=26.90,P=0.001;I2=70.3%].ThefunnelplotshowninFigure3reflectsthepublicationbiasbyvisualinspection.TheresultsofEgger'stestrevealednopotentialriskofpublicationbias(t=−1.25,P=0.252). FIGURE2 Figure2.Forestplotoftranscranialmagneticstimulationinterventionforsuicidalideation. FIGURE3 Figure3.Funnelplot.SMD,StandardMeanDifference. Depression Sevenstudiesprovidedscoresfordepressionaftertheintervention.AsshowninFigure4,themeta-analysisresultsshowedthatthedepressionscoresoftheTMSgroupwerestatisticallysignificantlylowerthanthoseofthecontrolgroup(SMD=−0.885,95%CI:−1.361to−0.409,P=0.012).Theheterogeneityofthestudieswashigh(heterogeneityχ2=35.67,P<0.001;I2=83.2%). FIGURE4 Figure4.Forestplotoftranscranialmagneticstimulationinterventionfordepression. SubgroupAnalysis TMSPattern Meta-analysisusingarandomeffectsmodelshowedthatcomparedwithiTBS(SMD=−0.207,95%CI:−1.041to0.627,P=0.627),thescoresforsuicidalideationinpatientswhoreceivedrTMSintervention(SMD=−0.47,95%CI:−0.849to−0.091,P=0.015)weresignificantlylowerthanthoseinthecontrolgroup(Table3). TABLE3 Table3.Subgroupanalysisofincludedstudies. Age Meta-analysisusingarandomeffectsmodelshowedthatcomparedwithage≥50years(SMD=−0.213,95%CI−0.460to0.035,P=0.092),suicidalideationscoresinthegroupaged<50yearswhoreceivedtheintervention(SMD=−0.498,95%CI:−0.972to−0.025,P=0.039)werestatisticallysignificantlylowerthanthoseinthecontrolgroup(Table3). IntensityThreshold Inthreesubgroupsofintensitythreshold120%,110%,and≤100%,theefficacyofTMSinterventionforsuicidalideationwasrepresentedbySMDsof−0.087(95%CI:−0.371to0.198,P=0.551),−0.207(95%CI:−1.041to0.627,P=0.627),and−0.681(95%CI:−1.191to−0.171,P=0.009),respectively(Table3). Frequency Meta-analysisusingarandomeffectsmodelshowedthatcomparedwiththehighfrequencygroup(SMD=−0.382,95%CI:−0.782to0.018,P=0.061),thescoresforsuicidalideationinthegroupwhoreceivedalowfrequencyofrTMS(SMD=−0.516,95%CI:−0.958to−0.074,P=0.022)werestatisticallysignificantlylowerthanthoseinthecontrolgroup(Table3). CumulativeMeta-Analysis Noobvioustimetrendwasobservedwhenapplyingthe“initialvs.follow-up”strategy(P=0.087)andregressionstrategyanalysis(regressioncoefficient=−0.05585,P<0.001).Theseresultsremainedrobustwhenthefirststudywasremovedandtheresultsrecalculated(regressioncoefficient=−0.04770,P<0.001;Figure5). FIGURE5 Figure5.Cumulativemeta-analysisplot.ES,EffectSize. SensitivityAnalysis Sensitivityanalysisoftheincludedstudiesshowedthatthepointeffectvaluesfellwithinthe95%CIofthefinaleffectvalues,whichwerestableandhadnosignificanteffectonthefinalconclusions(Figure6). FIGURE6 Figure6.Influenceanalysisofindividualstudies. Discussion ThepresentstudysystematicallyreviewedtheefficacyofTMSinreducingsuicidalideationindepression.Theresultsshowedthatcomparedwiththecontrolgroup,thesuicidalideationscoresofthegroupreceivingTMStreatmentwerestatisticallysignificantlylower.TheresultsshowedthatTMSwasalsosignificantlyeffectiveinalleviatingdepression.Insummary,oursurveyoftheexistingresearchdemonstratedthattheuseofTMSinmanagingsuicideriskwaspromising,providingnewevidenceoftheeffectivenessandsafetyofTMSforalleviatingsuicidalideation. Ourresultsshowedmoderateheterogeneityamongtheincludedstudies.ToexplorepossibleinfluencesontheeffectivenessofTMSforreducingsuicidalideation,weperformedsubgroupanalysesaccordingtoTMSpattern,age,thresholdoutputrate,andfrequency.Theresultsshowthatthesevariablesareindeedalsoasourceofheterogeneityinthisstudy.Heterogeneitywashigh(I2=70.3%),andthefunnelplotshowedthattheoutliersappearedtobefromthesamesource(Figure3).Wefoundthearticle(38)thatwasthemainsourceofheterogeneityandusedittodrawaGalbraithstarplot(Figure7),andtheSMDafterexcludingitwas−0.252(95%CI:−0.439to−0.066,P=0.008),withlowerheterogeneity(I2=10.6%).Apossibleexplanationforthismightbethatanovelneuro-navigationtechniquewasusedinthatstudytodeterminethecoillocationforTMStreatment,ratherthanusingthetraditional5cmmethod.Thisdidnothaveanimpactontheoveralleffect. FIGURE7 Figure7.Galbraithstarplot. Althoughsubgroupanalyseswereperformedinourstudy,duetothelimitationsofthestudysize(non-significantgroupsarealwayssmall).Unfortunately,theresultsofsubgroupanalysesarelikelytobeunreliableintermsofbias.Ofconcern,thisalsosuggeststhatfuturestudiesofTMSresearchinterventionsforsuicideshouldpaymoreattentiontotheageofthesubjects,differentinterventionmodalities,anddifferentparametersettings. Cumulativeanalyseswereperformedinourstudyaccordingtothetimesequenceofthestudies,andmeta-analysisrepeatedforeachstudyadded,reflectingdynamictrendsinstudyresultsovertime.Theinterventioneffectwasshowntoberobust,andsensitivityanalysisalsoindicatedgoodstability(Sensitivityanalyseswereconductedbysequentiallyexcludingstudieswithmultipledailysessions,andtheresultswerethattheapparentefficacyofTMSonsuicidalideationdidnotvarywiththenumberofdailysessionsandwasrobust). TBSisaformofrTMSandthesestimulationparadigmshavebeenfoundtobesafeinnormalsubjectsandcapableofproducingconsistent,rapid,andcontrollableelectrophysiological,andbehavioralchanges(16,39).However,nostudieshaveshownthatiTBSwasamoreeffectiveinterventionthanrTMSinreducingsuicidalideation.Qinetal.whofoundthatrTMScouldachieveeffectiveoutcomesforolderadultswithdepression,butthattreatmentoutcomeswerenotasgoodasinyoungandmiddle-agedpatients.Inthestudybywalletal.,threeadolescentshadsuicidalideationandimprovedduringTMStreatment(40).StimulusintensityalsoinfluencestheeffectivenessofTMSinterventions,asdemonstratedbypreviousstudies(41,42).TherTMSmayactuate,inhibit,orsomehowotherwiseinterferewiththeactionofneuronalcorticalnetworks,dependingonstimulusfrequencyandintensity,andbrain-inducedelectricfieldsetup(43).Buttherelationshipbetweenthefrequencyandintensityofstimulationandtheinducedexcitabilitychangehasnotbeenextensivelyexplored.Inourstudy,thelowfrequencytargetwasalwaysontherightDLPFC,whilethehighfrequencytreatmenttargetwasalwaysontheleftDLPFCandlowfrequencytreatmentwasmorebeneficialinreducingsuicidalideationscoresindepressedpatientsthanthehigherfrequencies.Theeffectsofdifferentstimulationfrequenciesonthecortexarenotclear.Itiscommonlyassumedthathighfrequencystimulationincreasesneuronalactivityandcorticalexcitabilityinbrainregions(44),andthatlowfrequencystimulationdecreasesthem(45).However,noconsistentconclusionshavebeendrawnaboutthetherapeuticeffectsofdifferentstimulationfrequencies,andourconclusionsonthisweresimilartothosedescribedbyChenetal.(46)andLanaetal.(47). Comparedtootherphysicalinterventions,suchasECTinterventions,TMSinterventionsdonotseemtobeveryeffective(48).Themostencouragingresultssupportingtranscranialmagneticstimulationarethoseofstudies(49–51).Inafurtherstudy,DTMSwasusedinpatientswithsevereTRD,viaanew“H1”coildailyfor4weeks.DTMSwasassociatedwithimprovementsinsuicidalbehavior(ideationandbehavior),depressionandrelatedanxietysymptoms.TheclinicalsafetyofDTMSwasalsoconfirmed(52).Subjectsinallincludedstudiesweredepressed,andpatientsintwostudies(33,34)(iTBS)receivedphysicalinterventionswithoutmedication.CombinedwiththeresultsofthesubgroupanalysisoftheTMSmodel,thisseemstoimplythattheTMSinterventionispromisingasanadjunctivetreatment.Inonestudy,improvementswerefoundinbothsuicidalideation(especiallyinthefirstweekoftreatment)anddepressivesymptoms(50).Animprovementindepressivesymptomswasalsoshowninourmeta-analysisoftheresultsindepression(Figure4).Inapreviousstudy,areductioninsuicideriskwasfoundtobemediatedbyimprovementsindepressivesymptoms(49).Whileinanotherstudy,changesinsuicidalideationwerefoundtobeunrelatedtoimprovementsindepression(33),Weissmanetal.concludedthatthecorrelationbetweendepressionandchangesinsuicidalideationwas0.38andsuggestedthatsuicidalideationcouldbeaspecifictargetsymptomconstructforrTMS(53). ThisstudywasdesignedtodeterminetheeffectofTMStreatmentforreducingsuicidalideationindepression.Basedontheabovediscussion,aswellastheoutcomeindicatorsafterourquantitativeanalysis,webelievethattranscranialmagneticstimulationispromisinginreducingsuicidalideation.Thefindingssuggestedthatfutureresearchshouldfocusmoreonlow-intensity,low-frequencyTMSinterventionsforsuicidalideationinmiddle-agedyouth.However,duetothelimitationsofthisstudy,thisconclusionmaywarrantaseriouswarning,excepttosaythatthisstudyaddstotheevidenceforTMSinterventionsforsuicidalideationandprovidesapromisingdirectionforfutureresearchonTMSinterventionsinlargesamples. Thereweremanylimitationstothisstudy.Theunpublishedliteraturewasnotsearched,smallersamplesubgroupanalysisandthefunnelplotsuggestedthatpublicationbiasmayhaveresultedinanexaggerationofpositiveresults.Thisstudyfocusedonsuicidalideationratherthansuicidalbehaviororattempts,andalthoughSIisimportant,itisnottheonlyfactorthatcontributestosuicide.ItishopedthatmorefutureresearchwillfocusontheeffectsofTMSinterventionsonsuicidalbehaviororattempts.Finally,manystudieshaveprimarilyincludedtargetedtreatment-resistantdepression,anditisunclearwhetherSIinpatientswithoutTRDwillshowsimilarresults.Despiteitslimitations,thisis,toourknowledge,thefirstmeta-analysistoquantitativelyanalyzetheefficacyoftranscranialmagneticstimulationonsuicidal,whichisarguablyastrengthofthisstudy.AndthestudycertainlyaddedtoourunderstandingoftheefficacyofTMSinterventioninreducingsuicidalideationindepressionandprovidedvaluableadviceanddirectionforclinicaltreatment. DataAvailabilityStatement Theoriginalcontributionspresentedinthestudyareincludedinthearticle/SupplementaryMaterial,furtherinquiriescanbedirectedtothecorrespondingauthor/s. AuthorContributions YCwrotethefirstdraftofthismanuscriptandeditedthesubsequentversions.YC,HF,andXLareresponsibleforthedatacollectionandanalysis.CB,WG,XL,andFYgavecriticalrevisionforthemanuscript.Allauthorscontributedtothearticleandapprovedthesubmittedversion. Funding ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina(31771222)andtheNaturalScienceFoundationofAnhuiProvince(KJ2016A355). ConflictofInterest Theauthorsdeclarethattheresearchwasconductedintheabsenceofanycommercialorfinancialrelationshipsthatcouldbeconstruedasapotentialconflictofinterest. 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SupplementaryMaterial TheSupplementaryMaterialforthisarticlecanbefoundonlineat:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.764183/full#supplementary-material References 1.FerrariAJ,CharlsonFJ,NormanRE,PattenSB,WhitefordHA.Burdenofdepressivedisordersbycountry,sex,age,andyear:findingsfromtheglobalburdenofdiseasestudy2010.PLoSMed.(2013)10:e1001547.doi:10.1371/journal.pmed.1001547 PubMedAbstract|CrossRefFullText|GoogleScholar 2.FangX,ZhangC,WuZ,PengD,XiaW,XuJ,etal.Prevalence,riskfactorsandclinicalcharacteristicsofsuicidalideationinChinesepatientswithdepression.JAffectDisord.(2018)235:135–41.doi:10.1016/j.jad.2018.04.027 PubMedAbstract|CrossRefFullText|GoogleScholar 3.JunfengH,GuoL,BaihuiG,YuanyuanZ,XumeiW.Researchprogressofsuicideriskassessmentscaleabroad.IntJPsychiatry.(2015)042:135–8. 4.FleischmannA,DeLeoD.TheWorldHealthOrganization'sreportonsuicide:afundamentalstepinworldwidesuicideprevention.Crisis.(2014)35:289–91.doi:10.1027/0227-5910/a000293 PubMedAbstract|CrossRefFullText|GoogleScholar 5.WHO.FirstWHOReportOnSuicidePrevention.(2014).Availableonlineat:http://www.who.int/mediacentre/news/releases/2014/suicide-prevention-report/en/.(accessedMarch15,2021). 6.KlonskyED,MayAM,SafferBY.Suicide,suicideattempts,andsuicidalideation.AnnRevClinPsychol.(2016)12:307–30.doi:10.1146/annurev-clinpsy-021815-093204 PubMedAbstract|CrossRefFullText|GoogleScholar 7.FinkM,KellnerCH,McCallWV.TheroleofECTinsuicideprevention.JEct.(2014)30:5–9.doi:10.1097/YCT.0b013e3182a6ad0d PubMedAbstract|CrossRefFullText|GoogleScholar 8.CiprianiA,HawtonK,StocktonS,GeddesJR.Lithiuminthepreventionofsuicideinmooddisorders:updatedsystematicreviewandmeta-analysis.BMJ.(2013)346:f3646.doi:10.1136/bmj.f3646 PubMedAbstract|CrossRefFullText|GoogleScholar 9.ZalsmanG,HawtonK,WassermanD,HeeringenKV,ZoharJ.Suicidepreventionstrategiesrevisited:10-yearsystematicreview.LancetPsychiatry.(2016)3:646–59.doi:10.1016/S2215-0366(16)30030-X PubMedAbstract|CrossRefFullText|GoogleScholar 10.BrownGK,KarlinBE,TrockelM,GordienkoM,YesavageJ,TaylorCB.Effectivenessofcognitivebehavioraltherapyforveteranswithdepressionandsuicidalideation.ArchSuicideResOffiJIntAcadSuicideRes.(2016)20:677–82.doi:10.1080/13811118.2016.1162238 PubMedAbstract|CrossRefFullText|GoogleScholar 11.LefaucheurJP,AlemanA,BaekenC,BenningerDH,ZiemannU.Evidence-basedguidelinesonthetherapeuticuseofrepetitivetranscranialmagneticstimulation(rTMS):anupdate(2014–2018).ClinNeurophysiol.(2020)131:474–528.doi:10.1016/j.clinph.2019.11.002 PubMedAbstract|CrossRefFullText|GoogleScholar 12.ObermanL,EdwardsD,EldaiefM,Pascual-LeoneA.Safetyofthetabursttranscranialmagneticstimulation:asystematicreviewoftheliterature.JClinNeurophysiol.(2011)28:67–74.doi:10.1097/WNP.0b013e318205135f PubMedAbstract|CrossRefFullText|GoogleScholar 13.DiLazzaroV,DileoneM,PilatoF,CaponeF,MusumeciG,RanieriF,etal.ModulationofmotorcortexneuronalnetworksbyrTMS:comparisonoflocalandremoteeffectsofsixdifferentprotocolsofstimulation.JNeurophysiol.(2011)105:2150–6.doi:10.1152/jn.00781.2010 PubMedAbstract|CrossRefFullText|GoogleScholar 14.ChungSW,HoyKE,FitzgeraldPB.Theta-burststimulation:anewformofTMStreatmentfordepression?DepressAnxiety.(2015)32:182–92. PubMedAbstract|GoogleScholar 15.PrasserJ,SchecklmannM,PoepplTB,FrankE,KreuzerPM,HajakG,etal.BilateralprefrontalrTMSandthetaburstTMSasanadd-ontreatmentfordepression:arandomizedplacebocontrolledtrial.WorldJBiolPsychiatry.(2015)16:57–65.doi:10.3109/15622975.2014.964768 PubMedAbstract|CrossRefFullText|GoogleScholar 16.LazzaroVD,PilatoF,DileoneM,ProficeP,RothwellJC.Thephysiologicalbasisoftheeffectsofintermittentthetaburststimulationofthehumanmotorcortex.JPhysiol.(2010)586:3871–9.doi:10.1113/jphysiol.2008.152736 PubMedAbstract|CrossRefFullText|GoogleScholar 17.LiCT,ChenMH,JuanCH,HuangHH,ChenLF,HsiehJC,etal.Efficacyofprefrontaltheta-burststimulationinrefractorydepression:arandomizedsham-controlledstudy.Brain.(2014)137:2088–98.doi:10.1093/brain/awu109 PubMedAbstract|CrossRefFullText|GoogleScholar 18.TienY,HuangCW,ChanCH.RapidantisuicidaleffectsofprolongediTBSontreatment-resistantdepression:acasereport.PsychiatryRes.(2021)305:114264.doi:10.1016/j.psychres.2021.114264 PubMedAbstract|CrossRefFullText|GoogleScholar 19.SherL,MindesJ,NovakovicV.Transcranialmagneticstimulationandthetreatmentofsuicidality.ExpRevNeurother.(2010)10:1781–4.doi:10.1586/ern.10.166 PubMedAbstract|CrossRefFullText|GoogleScholar 20.BredemeierK,MillerIW.Executivefunctionandsuicidality:asystematicqualitativereview.ClinPsycholRev.(2015)40:170–83.doi:10.1016/j.cpr.2015.06.005 PubMedAbstract|CrossRefFullText|GoogleScholar 21.AllenK,BozzayML,EdenbaumER.Neurocognitionandsuicideriskinadults.CurrBehavNeurosciRep.(2019)6:151–65.doi:10.1007/s40473-019-00189-y CrossRefFullText|GoogleScholar 22.LuberB,LisanbySH.Enhancementofhumancognitiveperformanceusingtranscranialmagneticstimulation(TMS).Neuroimage.(2014)85:961–70.doi:10.1016/j.neuroimage.2013.06.007 PubMedAbstract|CrossRefFullText|GoogleScholar 23.YesavageJA,FairchildJK,MiZ,BiswasK,Davis-KarimA,PhibbsCS,etal.Effectofrepetitivetranscranialmagneticstimulationontreatment-resistantmajordepressioninUSveterans:arandomizedclinicaltrial.JAMAPsychiatry.(2018)75:884–93.doi:10.1001/jamapsychiatry.2018.1483 PubMedAbstract|CrossRefFullText|GoogleScholar 24.ChenY,MagninC,BrunelinJ,LeauneE,FangY,PouletE.Canseizuretherapiesandnoninvasivebrainstimulationspreventsuicidality?Asystematicreview.BrainBehav.(2021)11:e02144.doi:10.1002/brb3.2144 PubMedAbstract|CrossRefFullText|GoogleScholar 25.BozzayML,PrimackJ,BarredoJ,PhilipNS.Transcranialmagneticstimulationtoreducesuicidality–areviewandnaturalisticoutcomes.JPsychiatricRes.(2020)125:106–12.doi:10.1016/j.jpsychires.2020.03.016 PubMedAbstract|CrossRefFullText|GoogleScholar 26.SerafiniG,CanepaG,AgugliaA,AmerioA,BianchiD,MagnaniL,etal.Effectsofrepetitivetranscranialmagneticstimulationonsuicidalbehavior:asystematicreview.ProgNeuropsychopharmacolBiolPsychiatry.(2021)105:109981.doi:10.1016/j.pnpbp.2020.109981 PubMedAbstract|CrossRefFullText|GoogleScholar 27.BerlimMT,vandenEyndeF,Tovar-PerdomoS,DaskalakisZJ.Response,remissionanddrop-outratesfollowinghigh-frequencyrepetitivetranscranialmagneticstimulation(rTMS)fortreatingmajordepression:asystematicreviewandmeta-analysisofrandomized,double-blindandsham-controlledtrials.PsycholMed.(2014)44:225–39.doi:10.1017/S0033291713000512 PubMedAbstract|CrossRefFullText|GoogleScholar 28.BrunoniAR,ChaimaniA,MoffaAH,RazzaLB,GattazWF,DaskalakisZJ,etal.Repetitivetranscranialmagneticstimulationfortheacutetreatmentofmajordepressiveepisodes:asystematicreviewwithnetworkmeta-analysis.JAMAPsychiatry.(2017)74:143–52.doi:10.1001/jamapsychiatry.2016.3644 PubMedAbstract|CrossRefFullText|GoogleScholar 29.Dell'OssoB,OldaniL,CamuriG,DobreaC,CremaschiL,BenattiB,etal.Augmentativerepetitivetranscranialmagneticstimulation(rTMS)intheacutetreatmentofpoorresponderdepressedpatients:acomparisonstudybetweenhighandlowfrequencystimulation.EurPsychiatry.(2015)30:271–6.doi:10.1016/j.eurpsy.2014.12.001 PubMedAbstract|CrossRefFullText|GoogleScholar 30.GeorgeMS,RamanR,BenedekDM,PelicCG,GrammerGG,StokesKT,etal.Atwo-sitepilotrandomized3daytrialofhighdoseleftprefrontalrepetitivetranscranialmagneticstimulation(rTMS)forsuicidalinpatients.BrainStimulation.(2014)7:421–31.doi:10.1016/j.brs.2014.03.006 PubMedAbstract|CrossRefFullText|GoogleScholar 31.HigginsJ,ThompsonSG,DeeksJJ,AltmanDG.Cochranehandbookforsystematicreviewsofinterventionsversion5.1.0.thecochranecollaboration.Naunyn-SchmiedebergsArchivfexperimentellePathologieundPharmakologie(2008)5:S38. GoogleScholar 32.JadadA.Assessingthequalityofreportsofrandomizedclinicaltrials:isblindingnecessary?ControlClinTrials.(1996)17:1–12.doi:10.1016/0197-2456(95)00134-4 PubMedAbstract|CrossRefFullText|GoogleScholar 33.DesmyterS,DupratR,BaekenC,VanAutreveS,AudenaertK,vanHeeringenK.Acceleratedintermittentthetaburststimulationforsuicideriskintherapy-resistantdepressedpatients:arandomized,sham-controlledtrial.FrontHumNeurosci.(2016)10:480.doi:10.3389/fnhum.2016.00480 PubMedAbstract|CrossRefFullText|GoogleScholar 34.BaekenC,DupratR,WuGR,DeRaedtR,vanHeeringenK.Subgenualanteriorcingulate-medialorbitofrontalfunctionalconnectivityinmedication-resistantmajordepression:aneurobiologicalmarkerforacceleratedintermittentthetaburststimulationtreatment?BiolPsychiatryCognNeurosciNeuroimaging.(2017)2:556–65.doi:10.1016/j.bpsc.2017.01.001 PubMedAbstract|CrossRefFullText|GoogleScholar 35.QiW.TheEffectofHighandLowFrequencyRepetitiveTranscranialMagneticStimulationonClinicalSymptomsandSuicidalIdeationinPatientsWithDepression.Hebei:HebeiUniversity(2019). 36.JunBoG.EffectofRepetitiveTranscranialMagneticStimulationonSelfHarmofAdolescentDepression:AStudyontheEfficacyofLowFrequencyStimulationofRightDorsolateralPrefrontalLobe.Chengdu:UniversityofElectronicScienceandTechnology(2020). 37.DaiL,WangP,ZhangP,GuoQ,DuH,LiF,etal.Thetherapeuticeffectofrepetitivetranscranialmagneticstimulationinelderlydepressionpatients.Medicine.(2020)99:e21493.doi:10.1097/MD.0000000000021493 PubMedAbstract|CrossRefFullText|GoogleScholar 38.PanF,ShenZ,JiaoJ,ChenJ,LiS,LuJ,etal.Neuronavigation-GuidedrTMSforthetreatmentofdepressivepatientswithsuicidalideation:adouble-blind,randomized,sham-controlledtrial.ClinPharmacolTher.(2020)108:826–32.doi:10.1002/cpt.1858 PubMedAbstract|CrossRefFullText|GoogleScholar 39.HuangYZ,EdWardsMJ,RounisE,BhatiaKP,RothwellJC.Thetaburststimulationofthehumanmotorcortex.Neuron.(2005)45:201–6.doi:10.1016/j.neuron.2004.12.033 PubMedAbstract|CrossRefFullText|GoogleScholar 40.WallCA,CroarkinPE,SimLA,HusainMM,JanicakPG,KozelFA,etal.Adjunctiveuseofrepetitivetranscranialmagneticstimulationindepressedadolescents:aprospective,openpilotstudy.JClinPsychiatry.(2011)72:1263–9.doi:10.4088/JCP.11m07003 PubMedAbstract|CrossRefFullText|GoogleScholar 41.ToddG.Low-intensityrepetitivetranscranialmagneticstimulationdecreasesmotorcorticalexcitabilityinhumans.JApplPhysiol.(2006)101:500–5.doi:10.1152/japplphysiol.01399.2005 PubMedAbstract|CrossRefFullText|GoogleScholar 42.LangN,HarmsJ,WeyhT,LemonRN,PaulusW,RothwellJC,etal.StimulusintensityandcoilcharacteristicsinfluencetheefficacyofrTMStosuppresscorticalexcitability.ClinNeurophysiol.(2006)117:2292–301.doi:10.1016/j.clinph.2006.05.030 PubMedAbstract|CrossRefFullText|GoogleScholar 43.LefaucheurJP.Transcranialmagneticstimulation.HandbookClinNeurol.(2019)160:559–80.doi:10.1016/B978-0-444-64032-1.00037-0 PubMedAbstract|CrossRefFullText|GoogleScholar 44.DockxR,BaekenC,DupratR,VosFD,SaundersJH,PolisI,etal.Changesincaninecerebralperfusionafteracceleratedhighfrequencyrepetitivetranscranialmagneticstimulation(HF-rTMS):aproofofconceptstudy.VetJ.(2018)66:66–71.doi:10.1016/j.tvjl.2018.02.004 PubMedAbstract|CrossRefFullText|GoogleScholar 45.MilevRV,GiacobbeP,KennedySH,BlumbergerDM,DaskalakisZJ,DownarJ,etal.Canadiannetworkformoodandanxietytreatments(CANMAT)2016clinicalguidelinesforthemanagementofadultswithmajordepressivedisorder:section4.Neurostimulationtreatments.CanJPsychiatry.(2016)61:561–75.doi:10.1177/0706743716660033 PubMedAbstract|CrossRefFullText|GoogleScholar 46.ChenJ,ZhouC,WuB,WangY,LiQ,WeiY,etal.Leftversusrightrepetitivetranscranialmagneticstimulationintreatingmajordepression:ameta-analysisofrandomisedcontrolledtrials.PsychiatryRes.(2013)210:1260–4.doi:10.1016/j.psychres.2013.09.007 PubMedAbstract|CrossRefFullText|GoogleScholar 47.DonseL,PadbergF,SackAT,RushAJ,ArnsM.SimultaneousrTMSandpsychotherapyinmajordepressivedisorder:clinicaloutcomesandpredictorsfromalargenaturalisticstudy.BrainStimul.(2018)11:337–45.doi:10.1016/j.brs.2017.11.004 PubMedAbstract|CrossRefFullText|GoogleScholar 48.KeshtkarM,GhanizadehA,FiroozabadiA.Repetitivetranscranialmagneticstimulationversuselectroconvulsivetherapyforthetreatmentofmajordepressivedisorder,arandomizedcontrolledclinicaltrial.JEct.(2011)27:310–4.doi:10.1097/YCT.0b013e318221b31c PubMedAbstract|CrossRefFullText|GoogleScholar 49.CroarkinPE,NakoneznyPA,DengZD,RomanowiczM,VoortJLV,CamsariDD,etal.High-frequencyrepetitiveTMSforsuicidalideationinadolescentswithdepression.JAffectDisord.(2018)239:282–90.doi:10.1016/j.jad.2018.06.048 PubMedAbstract|CrossRefFullText|GoogleScholar 50.HadleyD,AndersonBS,BorckardtJJ,AranaA,LiX,NahasZ,etal.Safety,tolerability,andeffectivenessofhighdosesofadjunctivedailyleftprefrontalrepetitivetranscranialmagneticstimulationfortreatment-resistantdepressioninaclinicalsetting.JEct.(2011)27:18–25.doi:10.1097/YCT.0b013e3181ce1a8c PubMedAbstract|CrossRefFullText|GoogleScholar 51.AbdelnaimMA,LangguthB,DeppeM,MohonkoA,KreuzerPM,PoepplTB,etal.Anti-suicidalefficacyofrepetitivetranscranialmagneticstimulationindepressivepatients:aretrospectiveanalysisofalargesample.FrontPsychiatry.(2019)10:929.doi:10.3389/fpsyt.2019.00929 PubMedAbstract|CrossRefFullText|GoogleScholar 52.BerlimMT,VandenEyndeF,Tovar-PerdomoS,ChachamovichE,ZangenA,TureckiG.Augmentingantidepressantswithdeeptranscranialmagneticstimulation(DTMS)intreatment-resistantmajordepression.WorldJBiolPsychiatry.(2014)15:570–8.doi:10.3109/15622975.2014.925141 PubMedAbstract|CrossRefFullText|GoogleScholar 53.WeissmanCR,BlumbergerDM,BrownPE,IsserlesM,RajjiTK,DownarJ,etal.Bilateralrepetitivetranscranialmagneticstimulationdecreasessuicidalideationindepression.JClinPsychiatry.(2018)79.doi:10.4088/JCP.17m11692 PubMedAbstract|CrossRefFullText|GoogleScholar Keywords:transcranialmagneticstimulation,suicidalideation,meta-analysis,depression,TMS Citation:CuiY,FangH,BaoC,GengW,YuFandLiX(2022)EfficacyofTranscranialMagneticStimulationforReducingSuicidalIdeationinDepression:AMeta-Analysis.Front.Psychiatry12:764183.doi:10.3389/fpsyt.2021.764183 Received:25August2021;Accepted:20December2021;Published:18January2022. Editedby:HongmingLi,UniversityofPennsylvania,UnitedStates Reviewedby:MohamedA.Abdelnaim,UniversitätRegensburg,GermanyMelanieL.Bozzay,WarrenAlpertMedicalSchoolofBrownUniversity,UnitedStates Copyright©2022Cui,Fang,Bao,Geng,YuandLi.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(CCBY).Theuse,distributionorreproductioninotherforumsispermitted,providedtheoriginalauthor(s)andthecopyrightowner(s)arecreditedandthattheoriginalpublicationinthisjournaliscited,inaccordancewithacceptedacademicpractice.Nouse,distributionorreproductionispermittedwhichdoesnotcomplywiththeseterms. *Correspondence:FengqiongYu,[email protected];XiaomingLi,[email protected] COMMENTARY ORIGINALARTICLE Peoplealsolookedat SuggestaResearchTopic>