LAI: Linee guida ed esperienze internazionaliLlorca et al (2013) “Pa’ent Values and...

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