A concise reviewIBSWord文档下载推荐.docx
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A concise reviewIBSWord文档下载推荐.docx
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TOPICHIGHLIGHT
WJG20thAnniversarySpecialIssues(4):
Irritablebowelsyndrome
Irritablebowelsyndrome:
Aconcisereviewofcurrenttreatmentconcepts
WallGCetal.IBStreatmentreview
GeoffreyCWall,GinelleABryant,MichelleMBottenberg,ErikDMaki,AndrewRMiesner
GeoffreyCWall,GinelleABryant,MichelleMBottenberg,ErikDMaki,AndrewRMiesner,DepartmentofInternalMedicine,BroadlawnsMedicalCenter,DesMoines,IA50309,UnitedStates
Authorcontributions:
Allauthorsparticipatedinliteraturereview,retrieval,synthesisaswellaswritingthispaper
Correspondenceto:
GeoffreyCWall,PhD,FCCP,BCPS,CGP,DepartmentofPharmacy,IowaMethodistMedicalCenter,1200PleasantStreet,DesMoines,IA50309,UnitedStates.geoff.wall@drake.edu
Telephone:
+1-515-2414297Fax:
+1-515-2415085
Received:
September27,2013Revised:
March4,2014
Accepted:
June14,2014
Publishedonline:
Abstract
Irritablebowelsyndrome(IBS)isoneofthemostcommongastrointestinaldisorderscausingpatientstoseekmedicaltreatment.Itisrelativelyresourceintensiveandthesourceofsignificantmorbidity.RecentinsightsintothepathophysiologyandtreatmentofIBShasgivencliniciansmoreoptionsthanevertocontendwiththisdisorder.Thepurposeofourpaperistoreviewolder,"
classic"
treatmentsforIBSaswellasneweragentsand"
alternative"
therapies.WediscusstheevidencebaseofthesedrugsandprovidecontexttohelpdevelopappropriatetreatmentplansforIBSpatients.
©
2014BaishidengPublishingGroupInc.Allrightsreserved.
Keywords:
Irritablebowelsyndrome;
Probiotics;
Rifaximin;
Lubiprostone;
Linaclotide;
Peppermintoil
Coretip:
Gastroenterologypractitionershavemoreagentsthaneverbeforetotreatthesymptomsassociatedwithirritablebowelsyndrome.Unfortunately,despiteadvancesinourunderstandingofthepathophysiologyofthisdisorder,targetedtreatmentsdonotyetexist.Thisreviewsummarizestherecentevidence-basedtreatmentofthisdisorder,including,olderandneweragents.
WallGC,BryantGA,BottenbergMM,MakiED,MiesnerAR.Irritablebowelsyndrome:
Aconcisereviewofcurrenttreatmentconcepts.WorldJGastroenterol2014;
Inpress
INTRODUCTION
Irritablebowelsyndrome(IBS)isoneofthemostcommongastrointestinaldisorderscausingpatientstoseekmedicaltreatment.ItexertssignificanteconomicburdenandisresponsibleforconsiderablemorbidityinWesterncountries[1].Despitethesecostsandnumerousinvestigationsintothepathophysiologyandtreatmentofthisdisorder,ourunderstandingofIBSisstillincomplete.Overthelasttenyears,increasinginsightintotheentericnervoussystemandhowitsdysfunctionmayplayaroleinIBSpathologyhasemerged[2].AdditionallyourincreasingunderstandingofthegutmicrobiomeandhowitspotentialdisruptionmayleadtoIBSsymptomshasalsobeenhighlighted[3].However,withfewexceptions,theseinsightshaveyettoleadtotargetedtreatmentstrategiesforIBS.Currently,manyclinicians’useatreatmentapproachbasedonthepredominantsymptomsofthepatient:
constipation(IBS-C),diarrhea(IBS-D),ormixedsymptoms(IBS-M)(Table1)[4].SeveralnewdrugshaverecentlybeenexaminedforIBSusingthissymptom-basedapproach.TwoagentsforIBS-C,lubiprostoneandlinaclotidehavebeenapprovedbytheUnitedStates(US)FoodandDrugAdministration(FDA)forthatspecificindication[5].ToimprovetheevidencebywhichdrugsforIBSareapproved,theFDAhasrecentlyproposedstandardizedoutcomesforapprovalstudiesasisdiscussedlaterinthispaper.ThepurposeofthispaperistoprovidetheclinicianwithaconcisereviewofpharmacotherapystrategiesforIBS.Consequently,itisdividedintothreesections:
“classic”treatmentoptions,“newerdrugs,”suchaslubiprostoneandlinaclotide,and“alternative”treatmentssuchasprobioticsandpeppermintoil.Inthelastsectionwewillalsodiscussemerginginformationontheso-called“pre-cebo”effectinIBS.
CLASSICTREATMENTSFORIBS
Antidiarrheals
Loperamideisasyntheticopioid,whichactsonintestinalmusclestoprolongtransittimeandinhibitperistalsis.WhileloperamidehasbeenstudiedindifferentsubtypesofIBS,itmaybeparticularlyeffectiveinIBS-Dbecauseofitsabilitytodecreasefecalvolumeandtransittime.Ameta-analysisin2000foundloperamidetobeaneffectiveagentindecreasingstoolfrequencyandimprovingstoolconsistency,aswellasdemonstratingamodestimprovementinglobalwellbeing[6].However,itdoesnotappearthatloperamideiseffectiveinreducingabdominalpainincomparisontoplacebo.Infact,somestudiesshowanincreaseinabdominalpainparticularlywhenloperamideisusedinIBS-C[7].Othercommonantidiarrhealagents,suchasdiphenoxylatewithatropine,havenotbeenwellstudiedinIBSandarelikelytobelesstoleratedduetoanticholinergiceffects,suchassedation,drymouth,constipation,andurinaryretention.
Antidepressants
Antidepressants,suchasthetricyclicantidepressants(TCA),selectiveserotoninreuptakeinhibitors(SSRI),andserotoninnorepinephrinereuptakeinhibitors,havebeenutilizedinthetreatmentofvariousfunctionalgastrointestinaldisorders.CurrenttreatmentguidelinesendorsetheuseofeitherTCAsorSSRIsforpatientswithIBS,althoughduloxetinehasalsobeenstudiedinsmalltrialsforthispopulation[8,9].Theseagentsarebelievedtoactviacentrally-mediatedantinociceptivepathwaysdecreasingabdominalpainassociatedwithIBS.Inaddition,theseagentsmayaffectthegastrointestinaltractbyperipheralmeansparticularlyinguttransittimes[8].ArecentCochranereviewpooled15TCAandSSRItrials[10].Theantidepressantclassasawholesignificantlydecreasedpain,IBSsymptomscores,andoverallglobalassessment.AsubgroupanalysisrevealedonlyTCAsremainedstatisticallysignificantforabdominalpainandimprovementinsymptomscores.However,thismaybeduetoasmallernumberofpatientsandtrialsstudyingtheuseofSSRIstotreatIBS.Inaddition,anearliermeta-analysisdemonstratedareductioninpain,bloating,andothersymptoms,althoughitcontainedmostlyTCAtrials[11].
Despitethelargedifferencesintheamountofsupportingdata,manycliniciansarereticenttoprescribeTCAsinsteadofSSRIsgiventhepoortolerabilityoftheseagents.Infact,onetrialutilizingdesipraminefoundnearlyoneinfivesubjectsofthattreatmentarmdroppedoutduetoadversereactions[12].Secondaryaminetricyclicantidepressants(e.g.,nortriptyline)aretypicallybettertoleratedthantertiaryamines(e.g.,amitriptyline)becauseofdecreasedanticholinergicadverseeffects.Inaddition,lowerdosesofTCAsascomparedtodosesusedtotreatdepressionseemadequatetoprovideIBSsymptomrelief.Despiteamorefavorablesideeffectprofile,SSRIuseismorecontroversialinIBSpatientsasthesupportingevidenceisnotnearlyasrobust.ClinicalguidelinesdosuggesthypotheticallythatSSRIsmaybeofmoreutilityinIBS-CandTCAsmaybeofmorebenefitinIBS-Dduetotheirrespectiveeffectsonwholeguttransittimes[8].8Cliniciansawaithead-to-headtrialswiththeseagents.
Antispasmodics
MedicationsthatrelaxsmoothmuscleviaanticholinergicmechanismsorcalciumchannelantagonismhavebeencommonlyutilizedforthetreatmentofIBS.Amongthesearealverine,dicyclomine(withorwithoutcimetropium),hyoscyamine,otilonium,pinaverium,scopolamine,andtrimebutine.Theavailabilityofmanyofthesemedicationsvariesfromcountrytocountry.Generally,antispasmodicshavebeenutilizedfortheireffectsongastrointestinalmotilityinattemptstoreduceabdominalpainassociatedwithIBS.Theyhavealsobeenevaluatedincombinationwithagentssuchasacetaminophen,simethacone,andbenzodiazepinesinattemptstoimprovegastrointestinaldiscomfort[13-15].
Unfortunatelymanyofthestudiesevaluatingantispasmodicsaresmall,sufferfrommethodologicalissues,andoftenfailtoevaluateindividualsymptomsoreffectonIBSsubtypes.Onlyasmallnumberoftrialsincludeactivecomparators.ArecentCochranereviewof29antispasmodictrialsforIBSsuggestedthatsome,butnotallantispasmodicsmaydecreaseabdominalpain[10].Similarlysome,butnotall,antispasmodicsimprovedIBSsymptomscoresandglobalassessment.Asubgroupanalysisshowedbenefitoftheuseoftrimebutine,pinaverium,andcombineddicyclomine/cimetropiuminthetreatmentofIBS.Anticholinergicsideeffectsoftheseagentsoftenincludedose-relatedvisiondisturbances,drymouth,anddizziness.Moreover,antispasmodicscanalsocauseconstipation,thustheyshouldbeusedcautiouslyinpatientswithIBS-C.PrescribersshouldconsiderthelimitationsofthesemedicationswhenusingthemforIBS.
Bulkingagents
SeveralbulkingagentshavebeenexaminedinthetreatmentofIBS.Theseincludepsyllium,calciumpolycarbophil,bran,andispaghulahusk.Thesesyntheticandnaturallyoccurringfibersupplementsareoftenusedfortheirabilitytoincreasestoolfrequency,quality,andtransittime.Consequently,theyareoftenattractiveoptionsinallsubtypesofIBS,particularlyIBS-C.Mostofthetrialsinvolvingtheseagentshavebeensmallandasaresult,multiplemeta-analyseshavebeenundertaken.AnearlysystematicreviewfoundthattheremaybeasignificantimprovementinglobalIBSsymptomswithsolublefibers(psyllium,calciumpolycarbophil,ispaghula),butworseningsymptomswithinsolublefiber(bran)[16].However,thisreviewsufferedfromsignificantheterogeneity.Furthermore,arecentCochranereviewof12randomizedcontroltrialsshowedthatfibersupplem
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