LAI:Lineeguidaedesperienzeinternazionali
LAI:Guidelinesandinterna5onalexperience
PMLlorcaCHUClermont-Ferrand
EA7280UniversitéClermontAuvergne
Disclosures
• Advisoryboard:Allergan,Jansen,Lilly,Lundbeck,Otsuka,Roche,Teva
• Involvementinclinicaltrialsfor:Janssen,Lundbeck,Otsuka
• Educa5onalgrantsforresearch,honorariaandtravelsupportforac5vi5esasaconsultant/advisorandlecturer/facultymemberforpharmaceu5calcompanies:AstraZeneca,Janssen,Lundbeck,Otsuka,Sanofi
Objec5ves
• Interna5onalGuidelinesfortheuseofLAIinschizophrenia– TypeofGuidelines– Evolu5onofGuidelines
• AWtudesofPa5entstowardtreatmentandmorespecificallytowardLAI
• InterestofGuidelinesinclinicalprac5ce• Implementa5onofGuidelines
WhatareClinicalGuidelines?
• Meanstoimprovehealthcare
• 1990modernguidelineerabegan:– “systema'callydevelopedstatementstoassistprac''onerandpa'entdecisionsaboutappropriatehealthcareforspecificclinicalcircumstances”1
• Basedonbestavailableevidence
• Systema5cmethodsusedtoiden5fyandevaluatetheevidence
1.Fieldetal(1990)
TheEvidenceBasedMedicine(EBM)Triad
– Clinicaldecisionreliesonthreemaincomponents1:• Bestexternalevidence• Individualclinicalexperience• Pa5entValuesandexpecta5ons
1.Sacke@etal(1996)
“Gooddoctorsusebothindividualclinicalexper5seandthebestavailableexternalevidence,andneitheraloneisenough.Withoutclinicalexper5se,prac5cerisksbecomingtyrannisedbyevidence,forevenexcellentexternalevidencemaybeinapplicabletoorinappropriateforanindividualpa5ent.Withoutcurrentbestevidence,prac5cerisks
becomingrapidlyoutofdate,tothedetrimentofpa5ents.”1
Individualclinical
experience
Pa0entsvaluesandexpecta0ons
Bestexternalevidence
EBM
TheEBMtriad
“Bestexternalevidence”
InterestofEvidenceBasedGuidelinesfortheuseofLAI
Individualclinical
experience
Pa0entsvaluesandexpecta0ons
Bestexternalevidence
EBM
TheEBMtriad
Evidence-basedguidelines
• Evidence-basedguidelines(EBG)1:recommenda5onsdrawnupbyataskforceacercri5calanalysisofavailabledata(selectedandrankedaccordingtotheirlevelofevidence).– First-linetreatment:definedaccordingtoahigherlevelofevidence,(randomizedcontrolledtrials-RCT-)
– Second-orThird-linetreatments:basedonevidencefromnon-controlledornon-randomizedstudiesoronexpertadvice
1.Samalinetal(2012)
EBGcanbeconsideredaswayoforganizingthe“bestclinicalevidence”inrecommenda5onsofclinicalprac5ce
Evolu5onofEvidenceBasedguidelinesrelatedtoLAIusein
schizophrenia
AmericanPsychiatricAssocia5on
1. Lehmanetal(2010)
IntheupdateoftheAPAGuidelinesin2010,LAIwasonlyproposedincaseof
repeatednonadherenceforchronicpa0ents
EvidenceBasedguidelinesin2012InterestofLAIformaintenancetreatment
• Regardingnon-adherence,mostoftheguidelinesandalgorithms(exceptPORT2009)statedthatdepotan0psycho0csareeffec0veapproach1
• Someguidelines(CPA,2005;MOH,2011;NICE,2009;PORT2009)actuallyrecommendedthatswitchingformula0onofan0psycho0csfromoraltodepotshouldbeconsideredinthemaintenancetreatment.
1.Takeushietal(2012)
Alloftheguidelinesandalgorithmsfailedtocommentonwhetheroralordepothasaspecificinterest,exceptintermsof
adherence,inthemaintenancephaseoftreatment.
Evolu5onofguidelinesfortheWFSBP
20061 2012(MainlyRLAI&PP1M)2
“Atypicalortypicaldepotprepara5onsshouldbeatreatmentop5onwhenapa5entexpressesapreferenceforsuchtreatmentbecauseofitsconvenience,oranessen5alpartofatreatmentplaninwhichtheavoidanceofcovertnon-
adherencewithan5psycho5cdrugsisaclinicalpriority(LevelD)”
“Forop5mumeffec5venessinpreven5ngrelapse,depotprepara5onsshouldbe
prescribedwithinthestandardrecommendeddosageandintervalrange
(LevelA)”
“Thereisgoodevidencetosupporttheuseoflong-ac5nginjectableRisperidone
forthetreatmentofschizophrenia(CategoryofevidenceA,
Recommenda5ongrade1)”“Thereissomeevidencefortheuseoflong-ac5nginjectableRisperidonein
first-episodeschizophreniapa5entsandelderlypa5entssufferingfrom
schizophrenia(CategoryofevidenceB,Recommenda5ongrade3)”
1. Falkaietal(2006)2. Hasanetal(2013)
Evolu5onofguidelinesfortheRoyalAustralianandNewZealandCollege
ofPsychiatrists20051 20162
“Depotmedica5onshouldbereservedfortwogroups.Firstlythosewhoclearlyoptvoluntarilyforthisrouteofadministra5on.AtypicalinjectableagentsarepreferredbecauseofbeSertolerabilityandreduced
riskoftardivedyskinesia.Secondly,thosewhodespiteaseriesof
comprehensivepsychosocialinterven5onsaimedatpromo5ngadapta5onand
adherence,repeatedlyfailtoadheretonecessarymedica5onandrelapse
frequently”
“Long-ac5nginjectablean5psycho5cagentsshouldbeofferedtopa5entsearlyintheclinicalcourseofschizophrenia”“Long-ac5nginjectablean5psycho5c
agentsarerecommendedinthetreatmentofschizophreniaandfirst-episode
psychosis:Ø whenitistheindividual’s
preferenceØ aspartoftreatmentplanwhere
adherencehasbeenpoororuncertainØ aspartofthetreatmentalgorithmwheretherehasbeenapoorresponse
tooralmedica5on”
1. RANZP(2005)2. Galletlyetal(2016)
“Individualclinicalexperience”
InterestofConsensusBasedGuidelines
Individualclinical
experience
Pa0entsvaluesandexpecta0ons
Bestexternalevidence
EBM
TheEBMtriad
Consensus-basedguidelines
• Consensus-basedguidelines(CBG)1:recommenda5onsbasedontheadviceissuedfromtheknowledgeoftheliteratureandtheprac0calexperienceofapanelofexperts,whoareaskedtoconsiderspecificclinicalques5onsorsitua5ons:– Thismethodologyenablestheassessmentofclinicalsitua5onsforwhichevidence(fromrandomizedcontrolledtrials)arescarceordebated.
1.Samalinetal(2012)
CBGcanbeconsideredaswayofintegra5ngthe“individualclinicalexperience”ofexpertsinrecommenda5onsofclinicalprac5ce
1.Kaneetal(1998)
Whoshouldbeconsideredfordepotdrugs?Anypa0entforwhomlong-termtreatmentisindicatedreceivingshouldbeconsidered.Thosepa5entswhoareirregularintakingmedica0onsarepar5cularlygoodcandidates.Eveninpa5entswhoini5allyrefusethisop5on,cliniciansshouldworkwiththem(throughthetherapeu0calliance)tohelpthepa0entsunderstandthepoten0aladvantages.Whenshouldthetreatmentstart?Assoonaspossibleandfeasible,acertheimprovementofacutesymptoms…Whichdrug?Inchoosingwhichdrugtheclinicianshouldconsiderpreviousexperience,personalpa0entpreference,pa0entshistoryofresponse(boththerapeu5candadverseeffects)andpharmacokine5cproper5es.Thereisnodefiniteevidencethatanyonedepotdrugissuperiortoanotherintermsofefficacy,thoughtheymaydifferinsideeffectprofile.
“Guidelinesfordepotan5psycho5ctreatmentinschizophrenia”(ECNP)
Long-Ac5ngInjectableAn5psycho5cs:Recommenda5onsforClinicians1
CanadianPsychiatricAssocia5on• Specificproposi0ons
– ForAllPhases• “Theexistenceandpoten'aluseofLAIsforAPtherapyshouldbediscussedwithpa'entsandfamiliesatallphasesofillness,includingthecri'calperiodofthefirst2to5years.”
– InformedPa0entDecision• “Informa'onregardingLAIsshouldbecarefullyandsystema5callydiscussedwithpa5entsinacollabora5veenvironment,takingintoconsidera'onpa'ents’andtheirfamilies’viewsregardingsuchuse…Inallcases,pa5ents’opinionaboutthechoiceofanLAIshouldbeconsideredregardingknowledgeofitseffec'veness,easeofadministra'on,frequencyofinjec'ons,andcost.”
– ClinicalStabilityandPa0ents’ChangeinOpinionsandAXtudes• “Psychiatristsandothercliniciansshouldbepreparedtoseepa'ents’aatudestowardmedica'on,issuesrelatedtoadherencetotreatment,andneedforLAIsasproteanandnotsta'cphenomena.Aberaperiodofstability,pa'entsmaydevelopadifferentandmoreposi'veaatudetowardtheirtreatment,experienceanimprovedtherapeu'crela'onship,andbeinabe@erposi'ontoevaluatetheirop'onsoforal,comparedwithLAI,medica'ons.Hencecon5nueddiscussionregardingvariousformula5onsofmedica5onsisrecommended.”
1.Mallaetal(2013)
GuidelinesfortheuseandmanagementofLAIAPinseriousmentalillness1FrenchSocietyforBiologicalPsychiatry
• Keypoints– “LAIan'psycho'csareindicatedinpa5entswithschizophrenia,
schizoaffec5vedisorder,delusionaldisorderandbipolardisorder.– LAISGAarerecommendedasmaintenancetreatmentaZerthefirstepisode
ofschizophrenia.– LAIan'psycho'cshavelongbeenviewedasatreatmentthatcouldonlybe
usedforasmallsubgroupofpa'entswithnon-compliance,frequentrelapsesorwhoposearisktoothers.ThepanelconsidersthatLAIan'psycho'csshouldbeconsideredandsystema5callyproposedtoanypa5entsforwhommaintenancean5psycho5ctreatmentisindicated.
– InordertoimprovetheacceptanceandunderstandingofthebenefitsofanLAIan'psycho'c,itisrecommendedtodelivertoeachpa5entspecificinforma5onconcerningtheadvantagesandinconveniencesoftheLAIformula5on,intheframeworkofshareddecision-making.”
1.Llorcaetal(2013)
“Bestexternalevidenceandindividualclinicaljudgment”
InterestofEvidenceBasedGuidelinesandConsensusBasedGuidelines
Individualclinical
experience
Pa0entsvaluesandexpecta0ons
Bestexternalevidence
EBM
TheEBMtriad
Strengthsandlimita5onsofbothstrategies• EBG:
– Strengths• Developedfromscien5fic
evidence(notfromopinionorjudgment)
• Recommenda5onsareranked(basedonthelevelofevidence)
– Limita5ons• Nopossiblerecommenda5ons
ifthereisnoevidenceavailable
• CBG:– Strengths
• Applicableforthepa5enttreatedineverydayclinicalprac5ceandnotonlytopa5entsaccordingtherestric5veinclusioncriteriaofRCT
• Applicableinspecificsitua5onsforwhichthereisnoevidence(e.g.specificpopula5ons…)
– Limita5ons• Basedonopinionand
judgment• Difficultytodefineexper5se
1.Samalinetal(2012)
Bothareusefulandsynergicintermsofhelpforclinicians
Evolu5onofGuidelines
• Duringthelast15yearsEvidenceBasedGuidelines(EBG)andConsensusBasedGuidelinesCBG)bothhighlighted:– TheinterestofLAInotonlyin
caseofnonadherenceandmul0plerelapses
– TheinterestofanearlieruseofLAIasanewparadigminthetreatmentofschizophrenia
• Thisevolu0onisbasedon:– Newevidencesandmore
specifically2RCTs1,2– Newexperts’consensusin
variouscountries3,4 1. Subotniketal(2015)2. Schreineretal(2015)3. Mallaetal(2013)4. Llorcaetal(2013)
“Pa'entValuesandexpecta'ons”
Pa5entsaWtudestowardsLAI
Individualclinical
experience
Pa0entsvaluesandexpecta0ons
Bestexternalevidence
EBM
TheEBMtriad
Pa5ents’aWtudestowardtreatmentInterestinclinicalprac'ce
• BeliefsaboutMedicinesQues0onnaire(BMQ)1canbeused:2– ToevaluateaXtudestowardtreatmentusing2specificsubscales(NecessityandConcern)
– Todefine4groupsofaWtudestowardtreatment:• Accep0ng• Ambivalent• Indifferent• Skep0cal
– Toiden0fytherela0onbetweenaXtudeandadherencetotreatment
1. Horneetal(1999)2. Samalinetal(2017)
Rela5onbetweenadherenceandaWtudes
Highnecessity
Lownecessity
HighconcernsLowconcerns
Ambivalentn=44(36.7%)
Accep0ngn=46(38.3%)
Skep0caln=22(18.3%)
Indifferentn=8(6.7%)
Adherence:• Low/medium:86.4%• High:13.6%
Adherence:• Low/medium:37.5%• High:62.5%
Adherence:• Low/medium:50.0%• High:50.0%
Adherence:• Low/medium:30.4%• High:69.6%
Beliefs
Choiceofatreatmentwithalowlevelofside
effects
Interestofapsychoeduca5on
program
Interestofcarefulmonitoringofadherence
1.Samalinetal(2016)
Crosssec5onalstudy(n=120)1Evalua0onofaXtudestowardtreatment,adherence,insightandsymptomatology,andsideeffects
AWtudesofpa5entstowardsLAIduringtheconsulta5on
• Ethnographicinforma5oncollectedfromanon-randomsampleof69prescriber-pa0entconversa0onsduringtreatmentvisits1:– 60withcommunitymental
healthcenterpsychiatrists– 9withnurse-prac55oners
• (14psychiatristsand60pa5ents)
1.Potkinetal(2013)
Pa5entsnaivetotreatmentaremoreneutralorfavorablethanunfavorabletoLAILAIswerenotdiscussedbypsychiatristsin50%ofpa0entstakingoral
an0psycho0cs.
AWtudesofpa5entsinanearlyinterven5onservicetowardsLAI
• Qualita5vestudyconductedinasampleof11pa5entsasendinganearlyinterven5onservice1:– Par5cipantsvaluedtheirpsychiatrist’srecommenda0onastothemost
appropriatean0psycho0c
– AWtudestoLAIsweremostposi0veamongthosecurrentlyreceivingaLAI
– LackofawarenessofLAIsasatreatmentop0onamongthosenotprescribedaLAI.
– Perceivedadvantages:• Convenience• AvoidingforgeXngtotaketablets
– Disadvantages:• Injec0onpain• Fearofneedles• Coercion
1.Dasetal(2014)
Inclinicalprac5ce…
AreGuidelinesusefulandaretheyused?
Areguidelinesuseful?
• Prescrip5onofAn5psycho5cs– Inacohortof2132pa5ents,con5nuousprescrip5onofAPaccordingtotheguidelines,inducesadecreaseofmortalitywhencomparedtopa5entstreatedinadiscon5nuousway1
• MonitoringofPhysicalHealth– Metaanalysisof48studies(n=290534)2
– Followingrecommenda5onsimproves:• Weightin75.9%ofthepa5ents• BPin75.2%ofthepa5ents• Glycemiain56.1%ofthepa5ents• Lipidprofilein28.9%ofthepa5ents
1. Cullen et al (2013) 2. Mitchell et al (2012)
Areguidelinesuseful?
StudydesignedtocomparetheimpactoftheuseofGLvs«treatmentasusual»(522pa5entstreatedduring12months)1
-Dusseldorf:Systema5cuseofGL+algorithmewithnumericsupport- Freiburg:Systema5cuseofGLnumericsupport- Munich1:«treatmentasusual(controlgroup)- Munich2:«treatmentasusual»+qualitymonitoring
PANSSposi5vesub-score PANSSnega5vesub-score
1. Janssen et al. (2010)
But…Aretheyused?• Guidelinesconcerningtheuseoftreatment
– Sampleof819schizophreniapa5ents1:• 52.3%areprescribed1AP• 47.7%areprescribedbetween2to4AP
• Guidelinesconcerningthephysicalhealthmonitoring– Metaanalysisof48studies(n=290534)2
– Monitoringof:• BPin69.8%ofthepa0ents• Triglyceridesin59.9%ofthepa0ents• Cholesterolin41.5%ofthepa0ents• Weightin47.9%ofthepa0ents
1. Stein et al (2012) 2. Mitchell et al (2012)
Despitetheinterestforpa5ents,mostofthecliniciansdonotfollowGuidelines….
HowtoimplementGuidelines…
1. Bighelli et al (2016)
Consequencesoftheimplementa0onoftreatmentguidelinesforspecialistmentalhealthcare1
Objec0ves:Examinetheefficacyofguidelineimplementa0onstrategiesinimprovingprocessoutcomes(performanceofhealthcareproviders)andpa5entoutcomes.Only6selectedstudies
Keypoints
• EBGandCBGconsideredLAIasavaluableop0oninthemaintenancetreatmentatallphasesoftheillness
• Pa5entsconsideredtheLAIasanop0on,buttheyfrequentlylackofinforma0on
• TheiraXtudesandknowledgehavetobeexplored
• GuidelinesimprovethequalityofCare,buttheyareinsufficientlyused…
• Needtobeac0velyimplemented
Ques5onwithmul5plechoice.1
• EvidencebasedGuidelinesrecommendtheuseofLAIinschizophrenia:1. Fornoncompliantpa5ent2. Forpa5entshavingapreferenceforthis
formula5on3. ForForresistantpa5ents4. Forpa5entsduringallthephasesoftheillness5. Forpa5entswithaddic5vecomorbidity
Ques5onwithmul5plechoice.1
• EvidencebasedGuidelinesrecommendtheuseofLAIinschizophrenia:1. Fornoncompliantpa5ent2. Forpa5entshavingapreferenceforthis
formula5on3. Forresistantpa5ents4. Forpa5entsduringallthephasesoftheillness5. Forpa5entswithaddic5vecomorbidity
Ques5onwithmul5plechoice.2
• ConsensusbasedGuidelinesrecommendfortheuseofLAIinschizophrenia:1. Touseastrategyofshareddecisionmaking2. Tousehaveacon5nuousdiscussionwithpa5ents
abouttheuseofthisformula5on3. Toassociatethisstrategywithcogni5ve
remedia5on4. Toincludefamilyandcaregiversinthedecision
process5. NottouseitaceraFirstEpisodeofPsychosis
Ques5onwithmul5plechoice.2
• ConsensusbasedGuidelinesrecommendfortheuseofLAIinschizophrenia:1. Touseastrategyofshareddecisionmaking2. Tousehaveacon5nuousdiscussionwithpa5ents
abouttheuseofthisformula5on3. Toassociatethisstrategywithcogni5ve
remedia5on4. Toincludefamilyandcaregiversinthedecision
process5. NottouseitaceraFirstEpisodeofPsychosis
Ques5onwithmul5plechoice.3
• Whenevalua5ngaWtudestowardtreatmentinschizophreniapa5ents,theycancanstra5fiedin:1. Accep5ng2. Reluctant3. Ambivalent4. Indifferent5. Scep5cal
Ques5onwithmul5plechoice.3
• Whenevalua5ngaWtudestowardtreatmentinschizophreniapa5ents,theycancanstra5fiedin:1. Accep5ng2. Reluctant3. Ambivalent4. Indifferent5. Skep5cal
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