where do antipsychotics fit? october 2011 - increase in death for aps typical or atypical. 22,23,24...

Guidelines/ReviewsDementiaCCCDTD32006:

http://www.cccdtd.ca/ TxMildMod2008:

http://www.cmaj.ca/content/179/10/1019.full.pdf+html

1 TxSevereAlzheimers2008:

http://www.cmaj.ca/content/179/12/1279.full.pdf+html

2NICE(UK) 2006:

http://www.nice.org.uk/nicemedia/live/10998/30318/30318.pdf

OtherReviewsCognitiveImpairment:

http://www.rxfacts.org/professionals/CognitiveImpairment.php

Pt/CaregiverResourcesFirstLinkProgramAlzheimers- http://alzheimer.ca/saskatchewan/- http://www.alzheimer.ca/english/soc

iety/FirstLink.htm

RxFilesRelatedAnticholinergicDrugList3AntipsychoticChart4BPSDTxChart5CATIEADTrialSummary6HypersexualityTxChart7PsychotropicsNewsletter8

Highlights1)Assessformedicalcauses(eg.InfectionUTI,constipation,urinaryretention,delirium).

2)Lookfordrugcauses(esp.recentmeds,butalsoanticholinergicload)

3)Implementnondrugtxbeforeinitiatingdrugsifpatient/caregiverinnoimmediateharm.

4)Unrecognizedpain?Tryoralacetaminophen(650mgq6hwhileawake,or1300mgLAam&hs).

5)Onlycertainsymptomsarelikelytorespondtoantipsychotics:

severeagitation aggression psychosis6)Reassessneedforantipsychoticsafter~3monthsasbehavioursstabilize(stoppingsriskofadverseevents)

7)Cautionwithcombo&PRNoveruseofAPs

BackgroundIssuesBehaviouralandpsychologicalsymptomsofdementia(BPSD)createasignificantcaregiverchallenge.Keysymptomsincludeaggression,agitation,psychosisandmooddisorders.

Table1:CommonBPSDNeuropsychiatricsymptomsagitation*apathyaggression*,

verbal/physicalcallingout,screaminghostilitysexualdisinhibition

resistivewanderingintrusivenessrepetitivebehavioursvocalizationshoardingnocturnalrestlessness

emotionallabilityparanoidbehaviourspsychosis*,hallucinations/delusions

*symptomswithsomeevidenceforbenefitofantipsychotics

ApproachtoManagingBPSDo Documentthetargetsymptom(e.g.DOSform9)o Assessforanytriggeringfactors(SeeTable2)o Identifyifsymptomrequirestreatment(e.g.

isfamily/caregiverdisturbedorindanger?)o Usenonpharmacologicalmeasures

wheneverpossible(SeeTable4,nextpage.)o Ispainapossiblecontributingfactor?

o Tryregularacetaminophen;reassessat1wko Ifdrugtreatmentrequired:

o Tailortothetargetsymptom(s)o Considerpotentialharmso Startlow,goslow;reassessin37daysfor

bothbeneficialandanyadverseeffectso Trytaperingthedoseorstoppingdrugevery

3+months[taperby25%every12weeks].Somebehavioursdeclineasdiseaseworsens.

{Iftreatingacutedelirium,stopuponresolution!}

Table2:CommonTriggeringFactorsinBPSDPsychosocialDistressFearofdangerMisinterpretation

Feelingabandoned

Lossofautonomy

ParanoiaEnvironmentalBadcompanyBoredomConfusingsurroundings

Excessivedemands

Change/lackofroutine

Lightinginadequate

LonelinessNoise

MedicalB12/folicaciddeficiency

Hunger/thirstHypercalcemia

Hypothyroidism

Infection(UTI, pneumonia)

MetabolicNocturiaPainConstipation

Medications(e.g.ruleoutdruginduceddelirium)Anticholinergics10Benzodiazepines

CholinesteraseinhibitorsDigoxin

OpioidsSubstanceabuse&manyothers

WhatdoweknowaboutthebenefitsandrisksofpsychotropicmedsinBPSD?o Evidenceforpsychotropicuseislimitedand

allclasseshavelimitedefficacyandseriousadverseevent(SAE)concerns.(SeeTable3)ForanoverviewseeBPSDchart(Page4).5

WheredoAntipsychotics(APs)Fit?APeffectivenessinBPSDismodest&theirroleislimitedduetoSAEs.11,12,13,14 See CATIE-AD Trial Summary.6 o APs,bothtypical(e.g.haloperidol)&atypical

(risperidoneRisperdal,olanzapineZyprexa&quetiapineSeroquel),havebeenstudiedinBPSD.

o Placeboresponseratesoften~40%,reflectinghighratesofspontaneousresolution&thevalueofpsychosocialinputinsuchtrials.15

[ThemoreseverepatientsmayrespondbettertoAPs.]o Oftheseatypicalagentsrisperidonehasthe

mostevidenceforefficacy(aggression1mg/day&psychosis2mg/day).

13,16

SeriousAdverseEvents(SAEs)forallAPs.o SAEswithAPsincludestroke(OR:1.33.1)13,17,

seizures,EPSeffects,falls,drowsiness,cognitivedecline,pneumonia&death.

o Deathmaybewithatypical&conventionalAPsindementiabasedonRCTs(OR:1.21.6;AR1%/12wks;NNH=87/12wks).

13,18,19,20,21Howeverobservationaldataisequivocal;somesuggestnoincreaseindeathforAPstypicaloratypical.

22,23,24

Stoppinglongtermantipsychoticsreducedmortalityby~25%at2yearsinlongtermfollowuptotheDARTADRCT.25{n=165, age ~85; Alzheimers patients MMSE~11 on APs for 3months for BPSD; 2 arms: stop AP & switch to placebo vs AP use x12months; no significant difference in survival at 12 months; survival at 2yrs: 71% vs 46%; NNT=4 /2yrs; survivalover24.5yrs:54%vs38%,NNT=8,CI:542} o BPSDoutcomes:nostatisticaldifference

exceptverbalfluencybetterinpatientswhostoppedat6mos.26Theremayhavebeenindividualdifferences(e.g.inthemoresevere).

o Remember,ifantipsychoticuseisrestricted,alternativedrugscouldbejustasharmful!

Table3:RisksofVariousPsychotropicMedsBenzodiazepines:falls,fractures,confusionCarbamazepine:falls,manyDIs&sideeffectsAntidepressants:sodium,falls,osteoporosisOpioids:delirium;constipation,fractures,?CV27

AvoidtheuseofpsychotropicmedsforBPSDifatallpossible.Whenneeded,assessfortolerabilityin37days&reassessforpossibletaperand/ordiscontinuationevery3months.

Behaviour Management in Dementia Where Do Antipsychotics Fit?

October 2011 Reprinted February 2012

Table4:SelectNondrugTreatmentTips

Allowbehavioursthatarenotproblematic Oktowanderwithinlimits;delusionscanbeokInstituteapatientcenteredorrelaxedschedulethatallowsflexibilityforthepreferentialroutinesofeachpatient:

e.g.medicationtimes,meals,bathing,sleeptimes,activities Assessdaytimenaps:limit/avoidinmost,butmaybeokto

allowaggressivepatienttosleepwhileothersareawake Maketimeforregularexercisetorestlessness;referto

daytimeprogramsifavailable Encouragedailyactivitiestominimizesundowning(eg.

playingcards,gardening)Makeapositiveenvironmentthatavoidstriggeringfactors:

aromatherapy playmusicsuitabletotheindividual reducenoiseornumberofpersonsinroom removekeysfromviewifnolongerdriving distractpersonwithsnackoractivity ifwandering,ensurehouse/roometc.issafe,putbuzzerson

doors,providelight,fallrisk provideclock&calendarifconfusedregardingtime&date ifinappropriatesexualbehaviour,considerroomplacement

changestominimizeinteractionsofconcernMinimizeunnecessary&problemdrugs.ToolstoreviewincludetheBeerslist28,ortheSTART/STOPPCriteria.29,30,31,32

Difficultyswallowingcancausesevereagitation.Ifdrugnecessary,lookforbetterformulations(e.g.dissolvabletablets)

Asdiseaseadvancestowardtheendoflife,transitionovertocomfortcare,ratherthancurative/preventative

Reviewmedswithconsiderationforstoppingstatins,vitamins,herbals,bisphosphonates

ReviewBP&bloodsugargoals;toolowcanleadtofallsOnlydolabworkwhennecessaryProvidingaccesstofalseteeth,hearingaids&glassesmayreduceagitationinsomepatients,althoughtheoppositemaybetrueifpatientissoundsensitive,oriftheseaidsareconsideredbothersomebythepatient(esp.hearingaid)

AE=adverse events AP=antipsychotic BG=blood glucose BP=blood pressure CI=conficence interval ChEIs=cholinesterase inhibitors CV=cardiovascular CVAE=cerebrovascular adverse events DI=drug interaction DIN:drug identification number HS=bedtime OR=odds ratio pt=patient NNT=number needed to treat NPN=natural product number RCT=randomized controlled trial SAE=serious adverse events TX=treatment

FirstLinkpatient/familysupportprogramforAlzheimersHealthcareprofessionalscanreferpatients/familiestotheprogramRCTevidencefounda28%inrateofnursinghomeplacementover9.5yrs(HR=0.717;p=0.25)orabouta1.5yrdelayinplacementmedian.

33a,b

SleepInsomnia&DementiaSleeppatternsnaturallychangeasyougetolder.Olderadults:

o Sleepfewerhours&takelongertofallasleepo Sleeplessdeeply&wakeupmoreoftenduringthenighto Havemoretroubleadjustingtochangesinsleeping

conditions,suchasanewbedo Havechangesintheirsleepcycle Olderadultsspend

lesstimeinthemostrestfulstageofsleepSleepdisturbanceinAlzheimersDisease(AD)isverycommon;nocturnalsleepdisturbanceinADpatientsisoftenaccompaniedbyincreaseddaytimenapping,frequentlyindirectassociationwiththeextentofdementia7

AnafterdinnerwalkmayhelpinpromotingnighttimesleepInthelaterstagesofAD,patientsmayspend~40%oftheirtimeinbedawakeandasignificantproportionofdaytimehoursasleep.Thisdaytimesleepconsistsalmostexclusivelyofstage1&2sleep;itdoesnotreplaceorcompensateforthenighttimelossofslowwavesleep(SWS)orREMsleep6Cholinesteraseinhibitorscancauseinsomnia(&nightmares)3

ThepresentationsofabnormalnocturnalbehaviorinADoftenexceedthelimitsofwhatmightotherwisebetermedinsomniainanondementedgeriatricpopulation7BehaviouralinterventionshouldbetriedbeforepharmacologicalinterventionswheneverpossibleLimitdrugtxtoshortterm/intermittentusewheneverpossible

Agentssometimesusedforinsomnia,andtheirlimitations34

Melatonin(135mgpoHS) [LookforproductwithNPNorDIN.]Limitedshorttermevidence(over38wks)forbenefit.35,36

TrazodoneDESYREL(12.52550100mgpoHS)Limitedevidence.Historicallyusedforsundowning.Sedatingwithoutanticholinergiceffects.Minimaleffectonsleeparchitecture.AEsincludehypotension,especiallyinthosewithinteractingdrugsorcomorbidities.

MirtazapineREMERON(7.51530mgpoHS)Usefulwhenantidepressanteffectdesired.AEs: weightgain,anticholinergic

ZopicloneIMOVANE/RHOVANE(3.757.5mgpoHS) Similarineffecttobenzodiazepines.Someconsidersafer,butevidencelacking.AEsincludetolerance,dependence,bittertaste.

Benzodiazepines(e.g.temazepam,lorazepam;clonazepamlongacting)Effectiveforshorttermuse(e.g.3weeks);however,AEsincludetolerance,dependence,falls,confusion,disinhibition,etc.Generallydiscouraged!

{Avoid long-acting agents (e.g. clonazepam) unless daytime anxiety