Disclosures. Outline. Outline. A"(very)"brief"history"of"BPSD. Evolution)of)Nosology 3/28/18

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1 Disclosures The$Management$of$Behavioral$and$ Psychotic$Symptoms$(BPSD)$in$Dementia What$is$the$State$of$the$Science? Ipsit&V.&Vahia,&M.D. Medical&Director,&Geriatric&Psychiatry&Outpatient&Programs, McLean&Hospital! No$financial$relationships$! Collaboration$with$Apple$Inc.$on$a$research$project$ (technical$support$only)$! Presenting$findings$from$research$supported$in$part,$ by$the$uc$san$diego$(ucsd)$stein$institute,$ucsd$ RPC$iPad$Project,$John$A.$Hartford$Foundation,$and$ NIH Member&of&the&Faculty, Harvard&Medical&School What%are%the%behavioral%and%psychotic% How%do%we%assess%them Non>pharmacologic%approaches Pharmacology% What%are%the%behavioral%and%psychotic% How%do%we%assess%them Non>pharmacologic%approaches Pharmacology% A"(very)"brief"history"of"BPSD Evolution)of)Nosology Alois(Alzheimer((1906C07) Senile(Psychosis((earlyClate(1900s) Psychosis(of(Dementia((2002) Neuropsychiatric(Symptoms(of(AD((mid(2000s) Behavioral(and(Psychotic(Symptoms(of(Dementia((BPSD)((2005) Auguste'Deter'(1850/1906):'loss'of'memory,'hallucinations,'delusions Alzheimer)A,)Allg)Zeitschr)Psychiatry,)1906 Agitation Psychosis Depression/ Anxiety Insomnia/ Circadian(disruption 1

2 Psychosis Delusions:*simple,*paranoid,*non1bizarre 1 e.g.*accusations*of*infidelity,*accusations*of*theft,*claims*of* impersonation Hallucinations:*predominantly*visual*(rather* than*auditory) Complex*bizarre*psychosis:*ABSENT*(*e.g.* First*rank * symptoms*such*as*thought*broadcasting,*thought*insertion,*multiple* voices*conversing) Agitation Aberrant(Vocalization:(repetitive(requests,( moaning,(screaming Motor(Agitation:(pacing,(wandering,(moving(in( chair,(intrusiveness,(banging,(disrobing,(taking( others (possession:(redirect(able(vs.(non? redirectable Aggressiveness:(verbal(threats,(physical(towards( property,(assault Resistance(to(Care((washing,(dressing,(eating,( meds):(avoidance,(verbal(refusal,(striking(out Rosen,'Burgio'et'al,'Am'J'Geriatric'Psych,'1994 Peak%Frequency%of%Behavioral%Symptoms% With%Alzheimer%Disease%Progression Peak$of$Occurrence$(%$Patients) Social$Withdrawal Depression Suicidal$ Ideation Paranoia Diurnal$ Rhythm Anxiety Agitation Wandering Socially$ Unacceptable Hallucinations Aggression 10!40$$$$$$$$$$$!30$$$$$$$$$$$!20$$$$$$$$$$$!10$$$$$$$$$$$0$$$$$$$$$$$10$$$$$$$$$$$20$$$$$$$$$$$30 0 Months$Before$and$After$Diagnosis Jost%BC,%et%al.%J"Am"Geriatr"Soc.%1996;44: What%are%the%behavioral%and%psychotic% How%do%we%assess%them Non>pharmacologic%approaches Pharmacology% Case DICE%Approach%for%Assessing/Managing%BPSD 67#year#old#male,#diagnosed#with#Alzheimer s#disease#6# years#ago,#living#with#wife#at#home,#retired#accountant Two#month#history#of#insomnia,#irritability#and#physical# restlessness#and#pacing#especially#late#in#the#day# One#week#of#talking#to# imaginary#people#in#his#home # and#increased#noncspecific#confusion#per#wife s#report No#significant#past#medical#history Medications:#Donepezil#10#mg#per#day,#Memantine#10# mg#twice#daily,#mirtazapine#15#mg#bedtime DESCRIBE'the'symptoms INVESTIGATE'the'cause CREATE'an'appropriate'plan' EVALUATE'the'plan Kales&et&al.&J&Am&Geriatr&Soc&62: ,&

3 3/28/18 Operationalizing-the-DICE-Approach-to-BPSD CharacterizeSymptoms Type Frequency Severity Pattern Timing ClinicalAssessment Clinical5History Lab5Panel Medications Standard5 scales (sensor5data) Establish Etiology Individualized Plan Psychosis: Medical5Cause (Delirium) Treat Psychiatric5Cause/ Meds Other5modifiable Factors Pain Hunger Noise Boredom Sensory5 deprivation Other5unmet5 needs What%are%the%behavioral%and%psychotic% How%do%we%assess%them Non>pharmacologic%approaches Pharmacology% Standardized*Measures ) Neuropsychiatric1Inventory1Questionnaire1(NPI)Q) ) Brief1Psychiatric1Rating1Scale1(BPRS) Agitation ) Pittsburgh1Agitation1Scale1(PAS) ) Cohen1Mansfield1Agitation1Inventory1(CMAI) Modify Depression ) Geriatric1Depression1Scale ) Cornell1Scale1for1Depression1in1Dementia Non$Pharmacological.approaches Treatment(of(Pain Enhanced(Communication(( Caregiver(Support(and(Resources Meaningful(Activities(for(patient Simplifying(Tasks Enhancing(or(Calming(environment Non$Pharmacological.Aids Systems'based+Approach 3 Study&of&a&videoconference3based& intervention&(echo3age)& providing&nursing&home&staff& access&to&consultation&with& geriatric&experts. 3 In&comparison&with&controls,& patients&treated&at&facilities&with& ECHO3AGE&had&17%&fewer& antipsychotic&prescriptions&and& 75%&less&likely&to&be&placed&in& restraints. Boston&Globe,&June&5,&2016 Gordon&et.al.,&JAMDA,&2016 3

4 Late%April%2013! Dinner'at'Kensington'Grill,'San'Diego'with'friends'and'their' boisterous'4'year'old! iphone'used'to'keep'him'calm'during'dinner Can%an%iPad%be%used%to%control% the%behavior%of%someone% functioning%at%the%level%of%a%4% year%old%i.e.%severe%dementia? Tablet'Devices'for'Controlling'Behavior'in'Dementia Conducted)on)UCSD)Senior)Behavioral)Health)Geriatric) Psychiatry)inpatient)unit Patients)with)history)of)behavioral)symptoms)(agitation)) who)required)psychotropic)medications) All)consented)patients)trained)in)iPad)use)by)staff Menu)of)approximately)70)apps) all)available) commercially)for)free)on)app)store When)patients)became)agitated,)devices)given)by) research)staff. Outcome)Measure:)feasibility)and)safety)data,)subjective) efficacy)of)app)use)(as)rated)by)staff) Vahia%et%al,%Am%J%Geriatr%Psych,%2014,%Supplement%1 Vahia%et%al%Am%J%Geriatr%Psych,%2016,%under%review Tablet'Devices'for'Controlling'Behavior'in'Dementia Tablet'Use'Among'Inpatients'with'Dementia Vahia%et%al,%2016,%Am%J%Geri%Psych,%under%review Tablet'Use'Among'Inpatients'with'Dementia What%are%the%behavioral%and%psychotic% How%do%we%assess%them Non>pharmacologic%approaches Pharmacology% Vahia%et%al,%2016,%Am%J%Geri%Psych,%under%review 4

5 Triggers'for'Antipsychotic'use'in'Dementia N=1769outpatients9at9the9Salem9VAMC,9Virginia The$Psychobehavioral$Metaphor Identification+of+the+hypothesized+underlying+ psychiatric+or+other+illness Examples: Depression irritability agitation Paranoia fear agitation Embarrassment disinhibition agitation 0 Agitation Delusion Hallucination Sleep9disturbance Irritability Pain+Disorder movement agitation Sapra%et.al.%Federal%Practitioner,%2012 Chronologic*Trends*in*Antipsychotic*Use American)Psychiatric)Association)(APA))Guidelines Assessing)Benefits)and)Risks)of)Antipsychotic)Treatment Non$emergency+Antipsychotic+medication+should+only+be+used+ for+treatment+of+agitation+or+psychosis+when+the+symptoms+ are+severe,+dangerous+and/or+cause+significant+distress+to+the+ patient Review+clinical+response+to+nonpharmacological+treatments+ prior+to+non+emergency+use+of+antipsychotics Prior+to+use,+potential+risks+and+benefits+should+be+reviewed+ by+the+clinician+and+discussed+with+the+patient+(if+feasible)+and+ their+surrogate+decision+maker(s)+with+input+from+family+and+ others Ventimiglia*J,*Kalali A,*Vahia*IV*and*Jeste DV,*Psychiatry*(Edgemont),*2010 American)Psychiatric)Association)(APA))Guidelines Dosing,)Duration)and)Monitoring)of)Treatment Treatment(should(be(initiated(at(a(low(dose(and(titrated( up(to(minimal(effective(dose If(a(clinically(significant(side(effect(from(antipsychotic( treatment(occurs,(potential(risks(and(benefits(should(be( reviewed(to(determine(whether(tapering(and( discontinuation(are(indicated If(there(is(no(clinically(significant(response(after(a(4<week( trial(of(an(antipsychotic,(treatment(should(be(tapered( and(withdrawn American)Psychiatric)Association)(APA))Guidelines Dosing,)Duration)and)Monitoring)of)Treatment If#there#is#significant#clinical#effect#on#BPSD,#attempt# should#be#made#to#taper#the#medication#after#4# months#unless#there#is#prior#history#of#relapse#upon# tapering. In#patients#whose#medication#is#being#tapered,# reassessments#should#occur#at#least#monthly,#and#for# at#least#4#months#after#taper to#assess#for#signs#of# relapse 5

6 American)Psychiatric)Association)(APA))Guidelines Use)of)Specific)Medications Expert'consensus'panel:'Which'of'the'following' prevented'you'from'using'antipsychotics'for'agitation? In#the#absence#of#delirium,#if#non#emergency# antipsychotic#treatment#is#indicated,#haloperidol# should#not#be#used#as#a#first#line#agent Long8acting#injectable#antipsychotic#should#not#be# used in#dementia#unless#indicated#for##co8occurring# primary#psychotic#disorder The$CATIE)AD$Study Comparing*risk*of*specific*agents: N"="421"(outpatients"with" AD"and"BPSD) Olanzapine (mean"dose"5.5" mg/day) Risperidone (mean"dose"1.0" mg/day) Quetiapine (mean"dose"56.5" mg/day) Placebo Time"to"discontinuation" for"inefficacy Risperidone:"26.7"wk Olanzapine:"22.1"wk Quetiapine:"9.1"wk Placebo:"9.0"wk Number'Needed'to'Harm: Haloperidol: 26 Olanzapine:' 40 Risperidone:' 27 Quetiapine:' 50 Antidepressant:'' 166 Schneider"LS"et"al."NEJM 2006;355:1525S38. What%if%Antipsychotic%Is%Stopped?! After&16&weeks&of&open& label&rx&&with&risperidone,& 180&patients&randomized& to&maintenance& risperidone versus&placebo! Relapse&in&first&16&weeks:& 60%&placebo&vs 33%& risperidone! Relapse&after&the&next&16& weeks:&48%&placebo&vs 15%&risperidone Devanand'DP,'et'al.'NEJM 20120'367: '' Long%Term%Effects%of%Antipsychotics Study&measured&time&to&nursing& home&placement&and&time&to& death&in&957&patients&with& diagnosis&of&probable& Alzheimer s&disease& Use&of&antipsychotics&was&not& associated&with&time&to&nursing& home&admission&or&time&to& death&after&adjustment&for& psychosis&and&agitation. Conclusion:&The&psychiatric& symptoms,&not&the&medications,& predict&time&to&nh&placement& and&death Lopez'OL'et'al.'Am#J#Psychiatry#20131'170:

7 Other&Agents:&Commonly&used Divalproex:, 3.out.of.4.placebo.controlled.trials.indicated.modest.benefit, most.frequently.used.in.combination.with. antipsychotics Citalopram:.The.CitAD Study.(Porsteinsson et.al,.jama,.2014). Other&Agents:&Limited/New&evidence Dextromethorphan:Quinidine&(Nuedexta)! NMDA&antagonist,&sigma!1&agonist,&5HT&and&NE&uptake& inhibitor&approved&by&fda&for&pseudobulbar&affect! 10!week&2!phase&RCT&with&N&of&194&found&clinically& significant&reduction&in&npi&scores&(cummings&jl&et&al,&jama&2015) Prazosin! Alpha!1&adrenergic&antagonist&known&to&be&efficacious&in& PTSD&found&in&one&small&open&trial&to&be&effective&for&BPSD.&! Average&dose&1!6mg.&No&parkinsonian&side&effects&but&may& cause&decrease&in&bp ECT: Other&Agents:&Novel&therapies Dronabinol Other&Agents:&Common&Agents Cholinergic+Agents:+may+decrease+visual+ hallucinations+and+apathy,+but+have+potential+ to+worsen+agitation.+ Benzodiazepines:+minimal+efficacy+data,+and+ high+risk+of+confusion,+falls+and+sedation.+ Occasionally+short+acting+(lorazepam)if+other+ options+fail.+ Antidepressants:+ mirtazapine+or+trazodone+ may+be+effective+if+depression+or+insomnia+are+ components+or+triggers Pharmacological+Approach:+Key+Points Anxiety(and(Non-specific(agitation(without(aggression(or( psychosis:(ssri(or(mirtazapine(or(trazadone(prn(if( episodic Agitation(or(aggression(with(psychosis:(atypical( antipsychotic( Agitation(or(aggression(with(depression:(SSRI,(SNRI(or( Mirtazapine Aggression(without(psychosis:(mood(stabilizer(or(atypical( antipsychotic Lewy-body(Disease:(Cholinergic(agents,(mood(stabilizers,( quetiapine,(clozapine Fronto-temporal(dementia:(Mood(stabilizers,(atypical( antipsychotics Summary BPSD%are%common,%disruptive,%primary%drivers%of% caregiver%burden%and%institutionalization.% Systematic%characterization%of%symptoms%in%each% individual%is%the%foundation%for%successful% management. Novel%technologies%have%a%potentially%major%role%in% management.% Non%pharmacologic%approaches%should%be%tried%first Pharmacologic%approach%should%be%tailored%based%on% symptom%profile%and%clinical%urgency The%newly%released%APA%practice%guidelines%provide%a% framework%for%use%of%antipsychotics%in%dementia.% 7

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