PharmacologicalManagementof

Behavioral&PsychologicalSymptomsofDementia

Investigate:TenKeyPoints1.  Neworrapidlyworseningbehavioralsymptomsinapatientwith

dementiashouldbeconsideredasignofanunderlyingmedicalillnessuntilprovenotherwise.

2.  Thefirststepinevaluationistoassesswhetherunderlyingmedicalfactorsmaybeinvolved.

3.  Problembehaviorsareoftentriggeredbyanticholinergicmedsandsuboptimalprescribing.

4.  Obtainacarefulhistoryfocusedonanychangesinthepatient’smedicalstatusandmedications.

Investigate:TenKeyPoints

5.  Therearedifferencesbetweenthepsychoticsymptomstypicallyseeninpatientswithdementiaversusthepsychosisseenotherconditions.

6.  “Psychobehavioralmetaphor”mayhelpselectaclassofmedicationmosthelpful.

7.  Incertainsituationsarisk-to-benefitanalysismaystillfavortheuseofantipsychoticmedications.

Investigate:TenKeyPoints

8.  Otherpossiblyhelpfulstrategies:prazosin(Minipress®)anddextromethorphan-quinidine(Nuedexta®).

9.  Theuseofbothpharmacologicalandbehavioralstrategiesleadstothebestresults.

10.  Symptomsevolveoverthestagesofdementiaandmaydecreaseordisappear.

CommonBehavioralProblems•FoodRefusal •Wandering •Restlessness

•Sleepdisturbances •Combativeness

•Disinhibition•Hypersexuality •Irritability

•Depression •Psychosis •ADLrefusal

•Socialwithdrawal •Medicationrefusal

•Anxiety •Agitation •Aggression

11

Types of Agitation

Agitation

Verbal

Aggressive e.g. Threats, name calling, profanity

Nonaggressive e.g. Repetitive requests, moaning

Physical

Aggressive e.g. Hitting, biting, scratching,

hair pulling, shoving

Nonaggressive e.g. Pacing, tapping, pounding

Cohen-Mansfield J, Marx MS, Rosenthal AS. A description of agitation in a nursing home. Journal of Gerontology: Medical Sciences 1989;44(3):M77–M84.

AppropriateEvaluationBehavioralsymptomsinapatientlivingwithdementiashouldbeviewedasaformofcommunication•  Symptomsoftenrepresenttheperson’sbestattempttosignalaproblem

•  Developmentofsymptomsshouldtriggeracarefulinvestigationtodeterminecause(s)

•  Symptomsoftenanindicationofunderlyingmedicalproblem

DifferentialDiagnosis:PatientRelated

Causesrelatedtothepatientcategorizedas:•  Medical:suboptimalprescribing,uncorrectedsensory

deficits,hypoglycemia,pain•  Psychiatric:depression,anxiety,paranoia•  Psychological:frustration,boredom,TVviolence,

loneliness•  Other:thirst,hunger,fatigue,noise,movement

restriction

DifferentialDiagnosis

•  Newmedicalconditions•  Pre-existingmedicalconditions•  Sub-optimalprescribing•  Poly-pharmacology•  Medicationnonadherence•  Newpsychiatriccondition•  Pre-existingpsychiatricconditionre-emerging•  Useofdrugsand/oralcohol

RecognizingDelirium•Havetherebeenanyrecentmedicationchanges?•Doesthepatientlookphysicallyillorphysicallyuncomfortable?•Arethepatient’svitalsignsreasonable?•Arethevitalsignsaroundtheirusualbaseline?•Arethepatient’slabvaluesreasonable?•Hasmentalstatuschangedrathersuddenlyordramatically?•Isthepatientsuddenlybehavinginwaysthathaveneverbeencharacteristicforthepatient?•Isthepatient‘slevelofalertnessand/orattentionwaxingandwaning?

Sub-OptimalPrescribing•  Prescribingamedicationfromanessentialcategoryofmedicationthatisnotseniorfriendly

•  Prescribingadoseofanessentialmedicationthatislargerthanneeded

•  Prescribingamedicationtobetakenatatimeofdaythatisnotoptimal(e.g.diureticsatbedtime)

•  Notprescribinganeededmedication(e.g.apainmedication)

•  Long-termuseofopiatepainmedicationinpatientsotherthanthosewithterminalcancer

Sub-OptimalPrescribing

Poly-pharmacy•  Avoidablemorbidityandmortality•  Canbecausedbynumerousprescriberswithlimitedcommunications

Sub-OptimalPrescribing

PrescribingCascade•  Medicationaddressesproblembutcreatessideeffects

•  Secondmedicationtreatssideeffectsbutmaycauseadditionalsideeffects

Ifnomedicalissuesidentified

Lookforco-occurrenceofpsychiatricconditions

•  Panicdisorder•  Depression•  Manicstate•  Paranoidpsychosis

PharmacologicalTreatmentofAgitation&Aggression

BestPracticesforPrescribing

•  Usemedicationsbettertoleratedbyolderadults•  Olderpatientsoftenneedlowerdosages•  Checktimingofmedicationdoseagainstotherissues,i.e.,diuretics

•  Omissionofmedications•  Opioidpainmedication–reducelongtermuse

BestPracticesforPrescribing

Beer’sCriteriaorBeer’sList

•  Listofmedicationsmoreharmfulthanhelpfulforolderpatients

•  Originallydevelopedin1997•  LatestversionsincooperationwithAmericanGeriatricsSociety

UseofPsychotropicMedications•  Trackimpactofmedication•  Startlowdosage•  Increaseslowly•  Alwaysuselowestpossibledose•  Incrementallyreducedoseandassessifbehaviorsreturn•  Symptomsmayrecedeoverdiseaseprogressionanduseof

medsmaynotbenecessary•  Maybepossibletodiscontinuemedication

UseofPsychotropicMedications•  Forallclassesofpsychotropics,preferenceformedications

thatarerenallyexcreted•  Benzodiazapinerarelyhelpfulforolderpatientsandshould

generallybeusedinatime-limitedmannerforsituationalsymptoms

•  Lookformedswithintermediatehalf-life•  Preferredbenzodiazapines:

–  Lorazepam(Ativan®)–  Oxazepam(Serax®)–  Temazepam(Restoril®)

UseofPsychotropicMedications

UsePDRasreferencetoolfor:

•  Appropriatestartingdosage•  Maximumdosage•  Sideeffects

AntipsychoticMedicationsDrug Dose

Aripiprazole(Abilify) 4formsincludingtablets(2,5,10,15,20,30mg),DiscMelt(10and15mg),liquidandIM

Asenapine(Saphris) 2.5mg&5mgsublingual;q12hours

Cariprazine(Vraylar) Capsules(1.5,3,4.5and6mg)

Clozapine(Clozaril) Refertopsychiatrist

Iloperidone(Fanapt) Tablets(1,24,6mg);q12hours

Lurasidone(Latuda) Tablets(20,40,60,80mg)

Olanzapine(Zyprexa) 4formsincludingtablets(2.5,5,7.5,10,15,20mg)Zydis(5,10,1520mg),IM,IMER

Paliperidone(Invega) Tablets(1.5,3,6and9mg)Max=12mg,Renal=3mg

Pimavanserin(Nuplazid) Tablet17mg(FDAforParkinson’sdiseasepsychosis

Quetiapine(Seroquel) Tabs(25,50,100,200mg)q12hours;Extendedreleasetabs(50,150,200,300,400mg)

Risperidone(Risperdal) 4formsincludingtabletsandM-Tabs(0.25,0.5,1,2,3,4mg),liquid,RisperdalConsta(q2weeks)

AntidepressantMedicationsDrug Dose

Citalopram 10,20and40mgtabs(20and40sarescored).Startingdoseis10mg.Maxdose=40mg.Dosesabove40mgnotrecommendedduetoQTcprolongation.

Escitalopram 5,10and20mg(10and20sarescored).Startingdoseis5mg.Maxdose=20.

Sertraline 25,50100tabsplusoralsolution.Startingdose=25mg.Maxdose=200mg.

Duloxetine 20,30,60mgtabs.Startingdose20mg.Maxdose=60mg.

NOTE:1)  Thesearegenerallyconsideredthebestchoicesforolderadultsbutother

factorslikeprevioustreatmenthistoryorfamilyhistorymayinfluenceyourchoice. 2)Ifyouprescribedanytwoantidepressantmedicationsforaparticularpatient

withoutsuccess,thenareferraltoapsychiatristisrecommended.

MoodStabilizingMedicationsDrug Dose

Divalproex Sprinkles125;,DR125,250500mg;ER250and500mg.Oralsolution:250mg/5ml.Startingdose=125to250mg.Doseisdeterminedbyclinicalresponseandbloodleveloftotalvalproicacid(50to100μg/ml).WhenconvertingtoER,increasedoseby20%.

Lithium Tablets,capsules,oralsolution;andER.300mgtabs.ERcomesin300and450s.Solution:8mEq/5ml.Recommendedtroughserumrangeis0.4to0.8mmol/L.Startingdose=300mg.

Gabapentin Capsules150,300,400mg;Tablets600and800;liquid.Startingdose150to300mg;Maxdose=3600mginadivideddose.

Pregabalin Caps:25mg,50mg,75mg,100mg,150mg,200mg,225mg,and300mg.OralSolution:20mg/mL.

Benzodiazepines•  Rarelyappropriateforlong-termuse•  Helpfulforacuteagitation•  Short-acting,renallyexcretedagentsarepreferred•  Occasionallymayuseclonazepam(Klonopin®)•  Smalldoses(e.g.lorazepam0.5mg)•  Worrisomesideeffects:delirium,clumsiness,falls,depression,tolerance,dependenceandwithdrawal

•  Rapidlydisintegratingformulationmaybehelpful

OtherMedications:

Trazodone(Desyrel®)•  Maytreatbothacuteagitationandpreventfurtherepisodes•  Maybegoodchoiceforinsomnia•  Doserange:25-100mg•  Completeresponsemaytake2-4weeks•  Sedationiscommon•  Priapismisveryrareinolderpatients

OtherMedications:Prazosin

Thenoradrenergicsystemisthebrain“adrenalin”systemforattentionandarousalDespitethelossofnoradrenergiclocusceruleusneuronsinADthereis

•  IncreasedCSFnorepinepherine(NE)•  IncreasedagitationresponsetoNE•  Increasedalpha-1adrenoreceptorsinlocusceruleus

Asaresult:ExcessivenoradrenergicreactivityproducesanxietyandagitationandmaycontributetoagitationinindividualslivingwithAD

OtherMedications:Prazosin

•  Prazosinisanalpha-1receptorantagonistØ TheonlyonethatcrossesfromthebloodintothebrainØ Non-sedatingØ DoesnotcauseparkinsonismbutmayreduceBPØ Showntohavelong-lastingbenefitsinPTSDØ Anopenlabeltrialandasmallplacebo-controlledtrialhavefoundthatitishelpfulintreatingagitationinNHresidentswithAD

Ø InAD,dosedbetween1-6mg/day

Dextromethorphane-Quinidine•  Dextromethorphanehydrobromideandquinidinesulfate

(Nuedexta®)isapprovedforpseudobulbaraffect(PBA)intheUSandEuropeanUnion

•  DextromethorphaneisØ Mostwell-knownasacoughsuppressantØ  alowlow-affinity,uncompetitiveNMDAreceptorantagonistØ  σ1(sigma1)receptoragonistØ  SerotoninandnorepinepherinereuptakeinhibitorØ Neuronalnicotinicα3β4receptorantagonist

•  QuinidineØ  isaClass1antiarrhythmicØ Whencombinedwithdextromethorphan,quinidineworksbyincreasingthe

amountofdextromethorphaninthebody

Dextromethorphane-Quinidine•  DosinginPBA

–  Thecombinationofdextromethorphan(20mg)-quinidine(10mg)comesasacapsuletotakebymouth.

–  Itcanbetakenwithorwithoutfood–  Startingdoseisonceadayfor7days–  After7days,itistakenevery12hours–  Morethan2dosesshouldnotbetakenina24-hourperiod–  Patientsshouldbesuretoallowabout12hoursbetweeneachdose–  Patientsshouldtakedextromethorphan-quinidineataroundthesametime(s)every

day–  Importantdrug-druginteractions:desipramine(levelsincrease8-fold),paroxetine

(2-foldincrease),MAOIsandmemantine

ChampionsforHealth.org/alzheimers

Websitetobeupdatedregularlywithmostcurrentinformation

Fundingforthiseducationalprogramprovidedby