12种新一代抗抑郁药

Articles:10.1016/S0140-6736(09)60046-51Comparativeefficacyandacceptabilityof12new-generationantidepressants:amultiple-treatmentsmeta-analysisAndreaCipriani,ToshiakiAFurukawa,GeorgiaSalanti,JohnRGeddes,JulianPTHiggins,RachelChurchill,NorioWatanabe,AtsuoNakagawa,IchiroMOmori,HughMcGuire,MicheleTansella,CorradoBarbuiSummaryBackgroundConventionalmeta-analyseshaveshowninconsistentresultsforefficacyofsecond-generationantidepressants.Wethereforedidamultiple-treatmentsmeta-analysis,whichaccountsforbothdirectandindirectcomparisons,toassesstheeffectsof12new-generationantidepressantsonmajordepression.MethodsWesystematicallyreviewed117randomisedcontrolledtrials(25928participants)from1991uptoNov30,2007,whichcomparedanyofthefollowingantidepressantsattherapeuticdoserangefortheacutetreatmentofunipolarmajordepressioninadults:bupropion,citalopram,duloxetine,escitalopram,fluoxetine,fluvoxamine,milnacipran,mirtazapine,paroxetine,reboxetine,sertraline,andvenlafaxine.Themainoutcomesweretheproportionofpatientswhorespondedtoordroppedoutoftheallocatedtreatment.Analysiswasdoneonanintention-to-treatbasis.FindingsMirtazapine,escitalopram,venlafaxine,andsertralineweresignificantlymoreefficaciousthanduloxetine(oddsratios[OR]1·39,1·33,1·30and1·27,respectively),fluoxetine(1·37,1·32,1·28,and1·25,respectively),fluvoxamine(1·41,1·35,1·30,and1·27,respectively),paroxetine(1·35,1·30,1·27,and1·22,respectively),andreboxetine(2·03,1·95,1·89,and1·85,respectively).Reboxetinewassignificantlylessefficaciousthanalltheotherantidepressantstested.Escitalopramandsertralineshowedthebestprofileofacceptability,leadingtosignificantlyfewerdiscontinuationsthandidduloxetine,fluvoxamine,paroxetine,reboxetine,andvenlafaxine.InterpretationClinicallyimportantdifferencesexistbetweencommonlyprescribedantidepressantsforbothefficacyandacceptabilityinfavourofescitalopramandsertraline.Sertralinemightbethebestchoicewhenstartingtreatmentformoderatetoseveremajordepressioninadultsbecauseithasthemostfavourablebalancebetweenbenefits,acceptability,andacquisitioncost.FundingNone.IntroductionInthepast20years,severalnewdrugshavebeenintroducedforthetreatmentofdepression,manyofwhicharestructurallyrelatedandsharesimilarputativemechanismsofaction.Aswithstatinsforthepreventionofcoronaryevents,1theextenttowhichtheseagentsvaryintermsofefficacyandacceptabilityisunclear.Moreover,someofthenewdrugsareso-calledme-toodrugs2—ie,chemicallysimilartoexistingdrugswithexpiringpatentsratherthangenuineadvancesintreatment.Systematicreviewshavealreadyhighlightedsomedifferencesinefficacybetweensecond-generationantidepressants.3–9Wereportanoverviewofallrandomisedcontrolledtrialsthatcompared12new-generationantidepressantsintermsofefficacyandacceptabilityintheacute-phasetreatmentofmajordepression.Weusedmultiple-treat-mentsmeta-analysis,10alsoknownasmixed-treatmentcomparisonsmeta-analysisornetworkmeta-analysis,whichallowstheintegrationofdatafromdirect(whentreatmentsarecomparedwithinarandomisedtrial)andindirectcomparisons(whentreatmentsarecomparedbetweentrialsbycombiningresultsonhoweffectivetheyarecomparedwithacommoncomparatortreatment).11Weaimedtoprovideaclinicallyusefulsummaryoftheresultsofthemultiple-treatmentsmeta-analysisthatcanbeusedtoguidetreatmentdecisions.MethodsStudyselectionanddatacollectionAtthebeginningofthisproject,wedraftedastudyprotocolandsubsequentlymadeitfreelyavailabletothepubliconourinstitutionalwebsitebeforecarryingoutthefinalanalyses.Furthermore,withthepublicationofthispapertheoveralldatasetwillbeinthepublicdomain.Forouranalysis,weincludedonlyrandomisedcontrolledtrialsthatcomparedanyofthefollowing12new-generationantidepressants(bupropion,citalopram,duloxetine,escitalopram,fluoxetine,fluvoxamine,milnacipran,mirta-zapine,paroxetine,reboxetine,sertraline,andvenlafaxine)asmonotherapyintheacute-phasetreatmentofadultswithunipolarmajordepression.Weexcludedplacebogroupswherepresentandrandomisedcontrolledtrialsofwomenwithpost-partumdepression.12Toidentifytherelevantstudies,wereviewedtheCochranecollaborationdepression,anxiety,andneurosisreviewgroupcontrolledtrialsregisters(CCDANDTR-studiesandCCDANCTR-references)uptoNov30,2007.PublishedOnlineJanuary29,2009DOI:10.1016/S0140-6736(09)60046-5SeeOnline/CommentDOI:10.1016/S0140-6736(09)60047-7DepartmentofMedicineandPublicHealth,SectionofPsychiatryandClinicalPsychology,UniversityofVerona,Italy(ACiprianiPhD,CBarbuiMD,ProfMTansellaMD);DepartmentofPsychiatryandCognitive-BehavioralMedicine,NagoyaCityUniversityGraduateSchoolofMedicalSciences,Nagoya,Japan(ProfTAFurukawaMD,NWatanabePhD,IMOmoriPhD);DepartmentofHygieneandEpidemiology,UniversityofIoanninaSchoolofMedicine,Greece(GSalantiPhD);DepartmentofPsychiatry,UniversityofOxford,UK(ACipriani,ProfJRGeddesMD);MRCBiostatisticsUnitInstituteofPublicHealth,UniversityofCambridge,UK(JPTHigginsPhD);CochraneDepression,AnxietyandNeurosisReviewGroup,InstituteofPsychiatry,London,UK(HMcGuireMA);DepartmentofCommunitybasedMedicine,UniversityofBristol,UK(RChurchillPhD);andDepartmentofNeuropsychiatry,SchoolofMedicin