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
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