Presentation on theme: "Rethinking Behavioral Problems Associated with Dementia"— Presentation transcript:
1 Rethinking Behavioral Problems Associated with Dementia Pennsylvania Medical Directors AssociationRethinking Behavioral Problems Associated with DementiaJoel E. Streim, M.D.Professor of PsychiatryUniversity of PennsylvaniaPhiladelphia VA Medical Center
2 Overview (of an evolving landscape) How will the new MDS 3.0 change assessment of behavioral symptoms of dementia?How can we identify more effective interventions based on an understanding that behaviors are triggered both byCognitive deficits due to dementia, as well asInternal and external factors?How should we interpret recent research to inform the use of medications to treat behavioral disturbances in dementia?
3 Overview of Changes from MDS 2.0 to MDS 3.0 Revised sections based on pilot studies :Cognitive PatternsDeliriumMoodBehaviorPainGait / fallsBladder and bowelHealth conditions
4 Minimum Data Set (MDS) Behavior Section Required completion on admission and at least quarterlyIncludes section on behavior problems in NH residentsMDS 2.0 based on staff observations and ratingsMDS 3.0 proposes a shift to the patients’ experiencePatients’ voice in depression assessmentPatients’ perspective / values in behavior assessment
5 Overview of Item Content in Behavior Section of MDS 3.0 CATEGORIESPsychotic SymptomsBehavioral SymptomsRejection of CareWanderingDOMAINSPresenceFrequencyAlterabilityImpact on residentImpact on othersChange from previous assessment
7 What makes this behavior a “problem”. Impact on the resident = clin What makes this behavior a “problem”? Impact on the resident = clin. significant
8 What makes this behavior a “problem”? Impact on Others
9 Rejection of Care: shifting emphasis to resident’s own values and goals
10 E6 - E9. Rejection of Care - Assessment Protocol Assess whether care rejection behavior is easily addressed or altered by modifying the approachIf not easily addressed or altered, determine whether care rejection behavior interferes with receipt of care that is necessary to meet resident’s (or proxy’s) goals for health and well-being.Advance healthcare directivesPreviously stated goals or preferencesChoices made by proxy on behalf of the resident
11 Wandering: impact and frequency determines whether problematic
12 E11a-b. Wandering - Impact Does the wandering place the resident at significant risk of getting to a dangerous place?Stairs, hazmat exposure, risk of getting lost, inadvertant exitingDoes the wandering significantly intrude on the privacy or activities of others?Interferes with ADLs, leisure activities, or staff restrict programming (group walks, other outings)
13 MDS 3.0 Field Testing and Validation Study Conducted in70 community nursing homes (n = 418 residents)20 VA nursing homes (n = 296 residents)“Gold standard” nurses administered MDS 3.0Facility nurses administered MDS 2.0Cohen-Mansfield Agitation Inventory (CMAI) was gold standard for validation of presence of behavioral symptomsNeuropsychiatric Inventory (NPI) was gold standard for validation of presence of psychosis
14 Comparison of Kappa Coefficients for MDS 2.0 vs 3.0 and CMAI Factor 10.2278( )0.8561( )Factor 20.3075( )0.7250( )Factor 30.2152( )0.3224( )
15 Factors that cause or contribute to behavioral problems associated with dementia
16 Assessment of behavioral symptoms in patients with dementia Behavioral symptoms are multiply determined byCognitive deficits due to dementiaInternal and external factors1. How does cognitive impairment lead to behavioral disturbances?2. What other factors contribute to behavioral disturbances?
17 Cognitive Domains Impaired in Dementia Syndrome of memory loss (amnesia)Decline in other cognitive functionsUse of language (aphasia)Visual-spatial functionRecognition (agnosia)Performing motor activities (apraxia)Initiating/executing sequential tasks (abulia, executive dysfunction)
18 How does memory impairment lead to behavioral problems? ExamplePatient is able to dress himself, but can’t remember where his clothes are keptWalks naked into hallway
19 How does language impairment (aphasia) lead to behavioral problems? ExamplePatient who can’t verbally communicate her dislike of milkThrows milk carton across the room
20 How does impaired recognition (agnosia) lead to behavioral problems? ExamplePatient can maneuver to pull down his pants, but can’t recognize that a toilet is a receptacle for urinationUrinates on floor near nurses station
21 How does impairment in performance of motor tasks (apraxia) lead to behavioral problems? ExamplePatient is continent of bladder, but cannot unzip or unbutton to pull down her pantsWets her clothing
22 Apraxia, Disability, and Behavioral Change in Terminal Stages of Dementia Examples:Patient no longer holds or manipulates objects (manual apraxia)Patient sits all day; has difficulty bearing weight and ambulating, even with assistance (gait apraxia)Patient can swallow, but cannot chew effectively (oral apraxia)
23 What other factors may contribute to behavioral changes in patients with dementia?
24 Common modifiable causes of behavioral disturbances Unmet needs (physical and psychological)Environmental / social irritantsAdverse drug effectsMedical conditions / somatic discomfortPsychiatric conditions
25 Unmet needs that can lead to behavioral disturbances Physical needsNutrition, hydration, toileting, exercise, restPsychological needsSecurity, autonomy, affection, self-worth
26 Environmental irritants that can lead to behavioral disturbances PhysicalNoiseConfusing visual stimuliUncomfortable temperatureUnfamiliar surroundingsSocialChanges in routinesProvocative social interactions
27 Adverse drug effects that can cause behavioral disturbances Nuisance symptomsAnticholinergic effectsAntihistaminic effectsParadoxical excitation / disinhibitionIntoxication or withdrawal statesAkathisia
28 Medical conditions and somatic discomfort that can lead to behavioral disturbances ArthritisDehydrationProstatic hypertrophyCOPDCerebrovascular diseaseCHFSomatic discomfortPainConstipationUrinary urgencyShortness of breathDizzinessFatigue
29 Psychiatric conditions that can cause behavioral disturbances DeliriumDepressionAnxietyPsychosis
30 Psychotic symptoms and agitation in dementia 10% to 73% have delusions21% to 49% have hallucinationsVisual hallucinations characteristic in Lewy Body dementiaSensory deprivation increases risk60% to 75% exhibit agitated behaviorFinkel. J Clin Psychiatry. 2001;62(suppl 21):3.Cohen-Mansfield and Billig. J Am Geriatr Soc. 1986;34:711.
31 So… if the patient has dementia with agitated behaviors associated with psychosis, is it appropriate to use antipsychotic medication in 2008?
32 Prior Evidence for Efficacy and Safety of Antipsychotic Drugs Meta-analyses of conventional antipsychotic drug studies found significant efficacy, but small effect sizes (Schneider et al, 1990)Efficacy studies of atypical antipsychotic drugs showed drug significantly better than placebo for psychosis, agitation, aggression (Katz et al 1999, Street 2000, Mintzer 2008)Atypical antipsychotics associated with less Parkinsonism; but sedation, gait disturbance and falls occur at higher doses
33 Regulatory Interpretation of Risks FDA warning about risk of diabetes (Sept. 2003)Applies to the class for all ages, conditionsFDA warnings about CVAEs (April 2003, Jan. 2004, March 2005)applies to risperidone, olanzapine, and aripiprazole in elders with dementiaFDA advisories about mortality (April 2005, June 2008)applies to atypical AND conventional antipsychotics in dementiaIncludes a reminder that these drugs are not FDA-approved for this indication
34 Risk of Cerebrovascular Adverse Events (CVAEs) in Elderly Patients With Dementia # of trialsCVAEsNumbers Needed to HarmActive drugPlaceboRisperidone43.8% (29/764)1.5% (7/466)44Olanzapine51.3% (15/1178)0.4% (2/478)118Aripiprazole31.3% (8/595)0.6% (2/343)112In US, letters to healthcare professionals were sent and warning added in prescribing informationUK Committee on Safety of Medicines guideline:Avoid use in BPSD of dementiaLimited to short-term and under-specialist advice for the management of acute psychotic conditions with risperidoneConsider risk in treating patients with previous history of stroke or transient ischemic attack and assess cerebrovascular disease risk factors including hypertension, diabetes, smoking, and atrial fibrillationIn 2 separate Health Canada Advisories, pooled analyses of 4 placebo-controlled trials of risperidone in dementia with 1230 patients and 5 placebo-controlled trials of olanzapine in dementia with 1662 patients demonstrated an increased risk of CVAEs with risperidone and olanzapine compared with placebo. Data from the advisory letters are presented on the slide.1,2In response to these findings, letters to US healthcare providers were sent and changes in the prescribing information of olanzapine and risperidone were made to include a warning on the increased risk as well as reminding clinicians that these agents are not approved for use in patients with dementia-related psychosis.3,4In the UK, the Committee on Safety of Medicines advised that risperidone and olanzapine should not be used for treatment of BPSD and that the use of risperidone for acute psychotic conditions in elderly should be limited to the short term and under specialist advice.5 Further, in patients with a previous history of stroke or transient ischemic attack, risk of cerebrovascular events should be carefully considered including risk factors such as hypertension, diabetes, current smoking, and atrial fibrillation.References: 1. Health Canada Advisory for Health Professionals. Risperdal® (risperidone) and cerebrovascular adverse events in placebo-controlled dementia trials. October 11, Available at: Accessed May 26, 2004; 2. Health Canada Advisory for Health Professionals. Zyprexa® (olanzapine) and cerebrovascular adverse events in placebo-controlled elderly dementia trials. March 10, Available at: Accessed May 26, 2004; 3. Risperdal® (risperidone) [package insert]. Titusville, NJ: Janssen Pharmaceutica Products, LP; 2003; 4. Zyprexa® (olanzapine) [package insert]. Indianapolis, Ind: Eli Lilly and Company; 2004; 5. Committee on Safety of Medicines. Atypical antipsychotic drugs and stroke. Available at: Accessed March 31, 2004.Health Canada Advisory for Health Professionals. Available at: dpt/risperdal1_e.html and Accessed May 26, 2004; Committee on Safety of Medicines. Available at: Accessed March 31, 2004.
35 Cerebrovascular Adverse Events: Pooled Analyses of Dementia RCTs Sample Size CVAEs Exposure RR (95% CI) subject-yrs(drug/PBO) (drug/PB0) (drug/PBO)Risperidone / / / ( )Olanzapine / / / ( )Aripiprazole / / / ( )Quetiapine / / / ( )Ziprasodone no available clinical trials data in dementia patientsHaloperidol ( )Re-order this wayOLRISARPQUEZIPNB: 95% CI includes 1 for nearly all drugs studied !!Adapted from Schneider L. Paper presented at Annual Meeting of the American Association for Geriatric Psychiatry, San Diego CA, March 5, 2005.
36 Mortality in Dementia Trials: Meta-analysis of RCTs Schneider examined 15 randomized, placebo-controlled trials6 were publishedMost were weeks durationSample3353 patients randomized to atypical antipsychotics1757 patients randomized to placeboDeath rates3.5% in treatment group2.3% in control groupRisk difference = 0.0195% Confidence Interval, (P=.01)Schneider LS, et al. JAMA 2005, 294:
37 Relative Risk of Death: Conventional vs. Atypical Antipsychotics Model Hazard Ratio (95% CI)Unadjusted analysis ( )Adjusted analysis*Use of any conventional APM ( )Low dose of conventional APM (<median) ( )High dose of conventional APM (>median) ( )Adjusted analysis of death**<40 days after beginning therapy ( )40-79 days after beginning therapy ( )days after beginning therapy ( )Adjusted analysis of patient subgroups**With dementia ( )Without dementia ( )In a nursing home ( )Not in a nursing home ( )*APM=antipsychotic medication CI=confidence interval**Hazard ratios adjusted for age, sex, cardiovascular and cerebrovascular disease, psychiatric disorders, other medications used, and residential status.Wang P et al. N Engl J Med. 2005;353:
38 Deaths per person-year Days after initiation of medicine Risk of Death in Elderly Patients: Atypical vs Conventional Antipsychotics0.6Conventional antipsychoticsAtypical antipsychotics0.50.4Deaths per person-year0.30.20.120406080100120140160180Days after initiation of medicineWang P et al. N Engl J Med. 2005;353:
39 CATIE-AD: Effectiveness of Atypical Antipsychotic Drugs in Outpatients with Alzheimer’s Disease 42-site, double blind, RCTN=421 patients with AD + psychosis, agitation or aggressionRandomized toOlanzapine (mean dose 5.5 mg/d)Quetiapine (mean dose 56.5 mg/d)Risperidone (mean dose 1.0 mg/d)PlaceboPrimary outcomes:Time to all-cause discontinuationNumber of patients with at least minimal improvement on CGIC at 12 weeksSchneider LS et al. N Engl J Med 2006;355:
40 CATIE-AD: Primary Outcomes No significant differences among groups on CGIC (P=0.22)No significant differences in time to discontinuation for any reason (P=0.52)Schneider LS et al. N Engl J Med 2006;355:
41 CATIE-AD: Summary of Results Time to discontinuation due to lack of efficacy favored olanzapine and risperidone (P=0.002)Time to discontinuation due to adverse events or intolerability favored placebo (P=0.009)Schneider LS et al. N Engl J Med 2006;355:
42 CATIE AD: ConclusionsAtypical antipsychotic drugs appear more efficacious than placebo, but…Adverse events limit overall effectivenessUse may be appropriate for patients who have no or few adverse effects, and for whom benefits can be discernedSchneider LS. Presented at Annual Meeting of the AAGP, March 2, 2007, New Orleans LA.
43 Incorporating Risk Tolerance in Making Treatment Decisions When is the balance between expected benefits and known risks acceptable to the patient or surrogate decision-maker?
44 Documentation is Crucial Inform patient or proxy of benefits and risksDiscuss acceptability of treatmentDocument discussion, including concurrence with treatment plan
45 Summary MDS 3.0 Behavior items Perform better than MDS 2.0 at detecting presence of target behaviorsClarify when behaviors are problemsRespect resident values and preferencesBehavioral symptoms in dementia may be explained byDeficits in various cognitive domainsOther factors such as unmet needs, environmental irritants, drug effects, medical and psychiatric conditions
46 SummaryAntipsychotic drugs may benefit selected nursing home residents, but it is advisable to:Discuss risks, including stroke and deathDocument that balance between expected benefits and known risks is acceptable to patient or proxy