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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

Member&of&the&Faculty,Harvard&Medical&School

Disclosures! 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

Outline

• What%are%the%behavioral%and%psychotic%symptoms%of%dementia%(BPSD)

• How%do%we%assess%them• Non>pharmacologic%approaches• Pharmacology%

Outline

• What%are%the%behavioral%and%psychotic%symptoms%of%dementia%(BPSD)

• How%do%we%assess%them• Non>pharmacologic%approaches• Pharmacology%

A"(very)"brief"history"of"BPSD

Alzheimer)A,)Allg)Zeitschr)Psychiatry,)1906

Auguste'Deter'(1850/1906):'loss'of'memory,'hallucinations,'delusions

Evolution)of)Nosology

Psychosis(of(Dementia((2002)

Neuropsychiatric(Symptoms(of(AD((mid(2000s)

Behavioral(and(Psychotic(Symptoms(of(Dementia((BPSD)((2005)

Alois(Alzheimer((1906C07)

Senile(Psychosis((earlyClate(1900s)

Agitation Psychosis Depression/Anxiety

Insomnia/Circadian(disruption

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Psychosis

• Delusions:*simple,*paranoid,*non1bizarre1 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

!40$$$$$$$$$$$!30$$$$$$$$$$$!20$$$$$$$$$$$!10$$$$$$$$$$$0$$$$$$$$$$$10$$$$$$$$$$$20$$$$$$$$$$$30

90

80

70

60

50

40

30

20

10

0 Months$Before$and$After$Diagnosis

Peak$of$Occurrence$(%$Patients)

Jost%BC,%et%al.%J"Am"Geriatr"Soc.%1996;44:107861081

Depression

Diurnal$Rhythm

Social$Withdrawal

Anxiety

Paranoia

Suicidal$Ideation

Agitation

Wandering Aggression

Hallucinations

Socially$Unacceptable

Outline

• What%are%the%behavioral%and%psychotic%symptoms%of%dementia%(BPSD)

• How%do%we%assess%them• Non>pharmacologic%approaches• Pharmacology%

• 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

Case DICE%Approach%for%Assessing/Managing%BPSD

DESCRIBE'the'symptoms

INVESTIGATE'the'cause

CREATE'an'appropriate'plan'

EVALUATE'the'planKales&et&al.&J&Am&Geriatr&Soc&62:762–769,&2014.

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Operationalizing-the-DICE-Approach-to-BPSD

• Type• Frequency• Severity• Pattern• Timing

Characterize-Symptoms

• Clinical5History• Lab5Panel• Medications• Standard5scales

• (sensor5data)

Clinical-Assessment

Medical5Cause(Delirium)

Psychiatric5Cause/Meds

Other5modifiableFactors• Pain• Hunger• Noise• Boredom• Sensory5

deprivation• Other5unmet5

needs

Treat

Modify

EstablishEtiology

IndividualizedPlan

Standardized*Measures• Psychosis:

) Neuropsychiatric1Inventory1Questionnaire1(NPI)Q)) Brief1Psychiatric1Rating1Scale1(BPRS)

• Agitation) Pittsburgh1Agitation1Scale1(PAS)) Cohen1Mansfield1Agitation1Inventory1(CMAI)

• Depression) Geriatric1Depression1Scale) Cornell1Scale1for1Depression1in1Dementia

Outline

• What%are%the%behavioral%and%psychotic%symptoms%of%dementia%(BPSD)

• How%do%we%assess%them• Non>pharmacologic%approaches• Pharmacology%

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

Boston&Globe,&June&5,&2016

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.

Gordon&et.al.,&JAMDA,&2016

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! Dinner'at'Kensington'Grill,'San'Diego'with'friends'and'their'boisterous'4'year'old! iPhone'used'to'keep'him'calm'during'dinner

Late%April%2013

Can%an%iPad%be%used%to%control%the%behavior%of%someone%

functioning%at%the%level%of%a%4%year%old%i.e.%severe%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)

Tablet'Devices'for'Controlling'Behavior'in'Dementia

Vahia%et%al,%Am%J%Geriatr%Psych,%2014,%Supplement%1Vahia%et%al%Am%J%Geriatr%Psych,%2016,%under%review

Tablet'Devices'for'Controlling'Behavior'in'DementiaTablet'Use'Among'Inpatients'with'Dementia

Vahia%et%al,%2016,%Am%J%Geri%Psych,%under%review

Tablet'Use'Among'Inpatients'with'Dementia

Vahia%et%al,%2016,%Am%J%Geri%Psych,%under%review

Outline

• What%are%the%behavioral%and%psychotic%symptoms%of%dementia%(BPSD)

• How%do%we%assess%them• Non>pharmacologic%approaches• Pharmacology%

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Triggers'for'Antipsychotic'use'in'Dementia

0

10

20

30

40

50

60

70

Agitation

Delusion

Halluc

ination

Sleep9

disturban

ce

Irritab

ility

N=1769outpatients9at9the9Salem9VAMC,9Virginia

Sapra%et.al.%Federal%Practitioner,%2012

The$Psychobehavioral$Metaphor

• Identification+of+the+hypothesized+underlying+psychiatric+or+other+illness

• Examples:– Depression++++++++++++irritability++++++++++agitation

– Paranoia++++++++++++++fear++++++++++++++agitation

– Embarrassment++++++++++disinhibition++++++++++agitation

– Pain+Disorder movement agitation

Chronologic*Trends*in*Antipsychotic*Use

Ventimiglia*J,*Kalali A,*Vahia*IV*and*Jeste DV,*Psychiatry*(Edgemont),*2010

American)Psychiatric)Association)(APA))GuidelinesAssessing)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

American)Psychiatric)Association)(APA))GuidelinesDosing,)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))GuidelinesDosing,)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

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American)Psychiatric)Association)(APA))GuidelinesUse)of)Specific)Medications

• 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

Expert'consensus'panel:'Which'of'the'following'prevented'you'from'using'antipsychotics'for'agitation?

The$CATIE)AD$StudyN"="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"wkOlanzapine:"22.1"wkQuetiapine:"9.1"wkPlacebo:"9.0"wk

Schneider"LS"et"al."NEJM 2006;355:1525S38.

Comparing*risk*of*specific*agents:

• Number'Needed'to'Harm:• Haloperidol: 26• Olanzapine:' 40• Risperidone:' 27• Quetiapine:' 50• Antidepressant:'' 166

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&vs15%&risperidone

Devanand'DP,'et'al.'NEJM 20120'367:149771507''

• 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

Long%Term%Effects%of%Antipsychotics

Lopez'OL'et'al.'Am#J#Psychiatry#20131'170:1051–1058

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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

Other&Agents:&Novel&therapiesECT:

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

• 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

Pharmacological+Approach:+Key+Points 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.%

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