Neuropsychiatric Symptoms of Dementia: Towards Understanding

Prevention and Treatment of Neuropsychiatric Symptoms of Dementia in LTC:Best Practices and Development of a LTC RESEARCH NETWORKDr. Dallas Seitz MD PhD FRCPCAssistant Professor and Division Chair,Division of Geriatric Psychiatry Department of Psychiatry, Queens UniversityBritish Columbia Psychogeriatric AssociationKamloops, BCApril 24, 20151Faculty/Presenter DisclosureFaculty: Dr. Dallas Seitz

Relationships with commercial interests:Grants/Research Support: CIHR, Alzheimers Association, Queens UniversityAdvisory Board: Eli-Lilly

2Disclosure of Commercial SupportThis program has received no in-kind support from outside organizations3Key ObjectivesBy the end of the presentation, the participant is expected to be able to:1.) Understand approaches to the assessment of neuropsychiatric symptoms (NPS) in dementia; 2.) Review recent evidence in non-pharmacological and pharmacological treatments for NPS; 3.) Introduce a research network focussed on NPS in LTC.

4Neuropsychiatric SymptomsNon-cognitive symptoms associated with dementiaAlso known as Behavioral and Psychological Symptoms of Dementia (BPSD)International Psychogeriatrics Association 1996 Signs and symptoms of disturbed perception, thought content, mood, or behavior that frequently occur in patients with dementia1

51. Finkel, Int Psychogeriatr, 1996; 8(suppl 3):497-500Alzheimers Association ClassificationAgitationinappropriate verbal, vocal, or motor activity that is not an obvious expression of need or confusion1PsychosisDelusions, hallucinationsDepressionApathyabsence of responsiveness to stimuli as demonstrated by a lack of self-initiated actionSleep6Cohen-Mansfield, J Gerontol, 1989

Prevalence of NPS in Alzheimers Disease7Prevalence in Past 30 DaysLyketsos, JAMA, 2002Prevalence of NPS in Long-Term Care60% of individuals LTC settings have dementia1Overall prevalence of NPS:Median prevalence of any NPS: 78%

81. Seitz, Int Psychogeriatr, 20102. Zuidema, J Geriatr Psych Neurol, 2007Prevalence of NPS2: Psychosis 15 30%Depression: 30 50%Physical agitation: 30%Aggression: 10 20%

Associations with Stage of Illness9Chen, Am J Geriatr Psychiatry, 2000 Percentage of Individuals with SymptomsPersistence of NPSNeuropsychiatric symptoms are often chronic1,2More likely to persist: delusions, depression, aberrant motor behaviorLess likely to persist: hallucinations, disinhibition10Steinberg, Int J Geriatr Psychiatry, 2004Aalten, Int J Geriatr Psychiatry, 2005Understanding NPS11

Kales, BMJ, 2015Psychological Theories of NPSLowered Stress Threshold1Learning Theory2Unmet needs Tailored interventions3Verbal agitation pain, depressionPhysically non-aggressive agitation - stimulationPhysically aggressive agitation avoiding discomfort

Hall, Arch Psych Nurs, 1987Cohen-Mansfield, Am J Geriatr Psych, 2001Cohen-Mansfield, Am Care Quarterly, 2000

12DICE Approach13

Kales, JAGS, 2014DICE APPROACH14

Kales, BMJ, 2015General Principles To Managing NPSNon-pharmacological treatments should be used first whenever availableEven when NPS are caused by specific etiologies (pain, depression, psychosis) non-pharmacological interventions should be utilized with medicationsAll non-pharmacological interventions work best when tailored to individual needs and backgroundFamily and caregivers are key collaborators and need to involved in treatment planning15IPA BPSD Guide, Module 5, 2010Nonpharmacological InterventionsTraining caregivers or Mental health consultationsParticipation in pleasant eventsExerciseMusicSensory stimulation (e.g. touch, Snoezelen, aromatherapy)

Cohen-Mansfield, Am J Geriatr Psychiatry, 2001Livingston, Am J Psychiatry, 2005Seitz, JAMDA, 201216Training Caregivers and StaffSome staff and caregiver training approaches are effective in reducing NPS1-3Also referred to as patient-centred careMost training programs involve psychoeducation about dementia symptomsCommunication strategies to avoid confrontationStrategies for redirection and distractionOften incorporate personalized pleasant events into interactions

McCallion, Gerontologist, 1999Chenoweth, Lancet Neurology, 2009Testad, J Clin Psychiatry, 201017Effects OF Caregiver Training on Agitation

18Chenoweth, Lancet Neurology, 2009Participation in Pleasant Events1-to-1 interaction with personalized pleasant events has been demonstrated to reduce NPS1Given 3X/week 20 30 minutes/sessionParticipation in group validation therapy may also be beneficial2

Lichtenberg, Gerontologist, 2005Toseland, J Appl Gerontol, 199719ExerciseExercise programs have been demonstrated to reduce NPS in LTC residents1-3Training caregivers in behavioral management and exercise program improved physical functioning of person with dementia and depressive symptoms430 minutes/day was recommendedExercise program included strength, flexibility, aerobic activity, balance

Alessi, J Am Geriatr Soc, 1999Landi, Arch Gerontol Geriatr, 2004Williams, Am J Alzheimer Dis Other Dementi, 2007Teri, JAMA, 2003

20MusicGroup music with movement or individualized music therapy are effective in reducing NPS1,230 minutes 2 3 times/ weekMay use prior to times of increased agitationPersonalized music more effective than generic music

Sung, Complement Ther Med, 2006Raglio, Alzheimer Dis Assoc Disord, 200821Sensory StimulationTherapeutic touch or gentle massage may relieve symptoms of agitation1,2Snoezelen (multisensory stimulation) providing tactile, light, olfactory, or auditory stimulation3Aromatherapy with massage 1 positive4 and 1 negative5 RCTHawranik, West J Nurs Pract, 2008Woods, Alter Ther Health Med, 2005Van Weert, J Am Geriatr Soc, 2005Ballard, J Clin Psychiatry, 2002Burns, Dementia Geriatr Cogn Disord, 201122Feasibility of Non-Pharmacological Interventions

23Seitz, JAMDA, 2012Pharmacological Management of NPSMedications should be used for severe NPS or patient safety, in conjunction with non-pharmacological approachesPrescribing requires assessment of capacity and informed consentDosages are lower than that used in younger populations and need to be adjusted cautiouslyElderly with dementia are more susceptible to some side-effects such as sedation, cognitive decline, EPSInternational Psychogeriatrics Association, BPSD Guide, Module 624Atypical AntipsychoticsRisperidone, aripiprazole, and olanzapine have the strongest evidence to treat psychosis and agitation in dementia1,2Number needed to treat for significant improvement: 5 14Odds ratio for significant improvement compared to placebo: 1.5 2.5

25Schneider, Am J Geriatr Psychiatry, 2006Ballard, Coch Database Syst Rev, 2008Fontaine, J Clin Psych, 2003Tariot, Am J Geriatr Psychiatry, 2006Verhey, Dementia Geriatr Cogn Disord, 2006Antipsychotics for Dementia:CATIE-AD Large RCT (N=421) of outpatients with Alzheimers comparing risperidone, olanzapine, quetiapine and placebo for psychosis, agitation or aggression over 36 weeksOutcomes:Time to discontinuation due to any causeGlobal impressionAdverse events

1. Schneider, New Eng J Med, 2006CATIE-ADNo difference in groups on time to discontinuation due to any causeOlanzapine and risperidone > placebo and quetiapine on discontinuations due to lack of efficacyOverall discontinuation rate of 63% by 12 weeksDiscontinuations due to adverse events favored placeboNo difference in rates of global clinical improvement1. Schneider, New Eng J Med, 2006NPS that Respond to AntipsychoticsOlanzapine and risperidone associated with overall improvement in NPS1Hostility, psychosis, agitation most likely to improve

1. Sultzer, Am J Psychiatry, 200828Serious Adverse EventsMortality: OR=1.6, absolute risk ~1%1,2Number needed to harm: 100Infections, cardiovascular eventsStroke: RR=2.7, absolute risk~1%2,3Any serious adverse events within 30 days4Atypical: 13.9% (OR: 3.5, 3.1 4.1)Typical: 16% (OR=4.2, 95% CI: 3.7 4.8)No antipsychotic: 4.4%Schneider, JAMA, 2005Schneider, Am J Geriatr Psychiatry, 2006 Herrmann, CNS Drugs, 2005 Rochon, Arch Intern Med, 200829COMPARATIVE SAFETY OF ANTIPSYCHOTICS30

Kales, JAMA Psychiatry, 2015UPDATED RISPERIDONE Indication31

Health Canada, February, 2015Common Adverse EventsSomnolence: OR=2.8, absolute risk~10%1Gait changes: OR=3.2, AR=10%1Falls and fractures: OR = 1.5 2.0Extrapyramidal symptoms1RisperidoneWeight gain, dyslipidemia2,3Greatest risk with olanzapine and quetiapine, women at highest risk

Schneider, Am J Geriatr Psychiatry, 2006Schneider, N Eng J Med, 2006Zheng, Am J Psychiatry, 200932Cognitive Effects of AntipsychoticsAtypical antipsychotics associated with a MMSE score -2.4 over 36 weeks compared to placebo1Equivalent to approximately 1 year additional declineMMSE -1 point over 8 12 week trials2Often LTC population with low MMSE at baseline

1. Vigen, Am J Psychiatry, 20112. Schneider, Am J Geriatr Psychiatry, 200633Typical AntipsychoticsEffective in reducing symptoms of aggression, agitation and psychosis1-3 Adverse event rates higher with typicals when compared to atypicalsRisk of stroke4,5 and death6,7 similar to atypical antipsychoticsSchneider, J Am Geriatr Soc, 1990Lanctot, J Clin Psychiatry, 1988Lonergan, Cochrane Data Syst Rev, 2002Gill, BMJ, 2005Herrmann, Am J Psychiatry, 2004Wang, N Eng J Med, 2005Gill, Ann Intern Med, 200734Selective Serotonin Reuptake InhibitorsSSRIs have some benefits in treating agitation, psychosis and other NPS1 (N=7)Citalopram more effective than placebo in reducing NPS2Doses of 20 30 mg daily (Note: FDA warning about citalopram doses above 20 mg daily)Sertraline had modest effect on agitation compared to placebo3Doses 25 100 mg daily

Seitz, Cochrane Data Syst Rev, 2011Pollock, Am J Psychiatry, 2002Finkel, Int J Geriatr Psychiatry, 200435Citalopram for Agitation: CITADRCT of citalopram (10 30 mg daily) or placebo for AD patient with significant agitationMajority received 30 mg of citalopram*Significant improvements on NBRS-A, CMAI with citalopram compared to placebo40% of citalopram vs 26% of individuals with placebo had moderate or marked improvementWorsening of cognition noted with citalopram

36Porsteinsson, JAMA, 2014Trazodone2 small RCTs of trazodone for NPS found no significant difference between trazodone and either placebo1 or haloperidol1-3Trazodone treated individuals had numerically worse outcomes when compared to placebo and haloperidolTrazodone was not associated with increased risk of major adverse eventsTeri, Neurology, 2000Sultzer, Am J Geriatr Psychiatry, 1997Seitz, Cochrane Data Syst Rev, 2011Cholinesterase Inhibitors for AgitationDonepezil had no effect in reducing agitation among individuals with significant agitation1Cholinesterase inhibitors not superior to antipsychotics in treating agitation2,3

Howard, New Eng J Med, 2007Holmes, Int J Geriatr Psychiatry, 2007Ballard, BMJ, 2005Freund-Levi, Dement Geriatr Cog Disorder, 201438Prevalence of Antipsychotic USe39

http://yourhealthsystem.cihi.ca/40

Canadian Geriatrics Society

www.choosingwiselycanada.org41

Discontinuing AntipsychoticsA large proportion of currently stable individuals on antipsychotics can have antipsychotics safely withdrawn1,2Withdrawal associated with 30% increase risk of behavioral worsening compared to placebo 1,2Predictors of successful discontinuation:Less severe NPS at initiation of treatment2Lower dose of antipsychotic required to treat NPS142Van Reekum, Int Psychogeriatr, 2002Ruths, Int J Geriatr Psychiatry, 2008Effects of Discontinuing Antipsychotics on Mortality

Ballard, Lancet Neurology, 2009Relapse Risk: ADAD TrialResponders to 16 weeks of treatment randomized to either continuation or placeboAcutely symptomatic population compared to previous studies of chronic antipsychotic treatmentRelapse rates at 16 weeks:Risperidone continuation: 2/13 (15%)Placebo: 13/27% (48%)Devanand, New Eng J Med, 2012Canadian Consortium On Neurodegeneration in AgingCCNA is a research hub for all aspects of research involving neurodegenerative diseases (including Alzheimers disease)$31. 5M dollars in funding from CIHR and $24M from partner organizations in ON and QC20 research teams including 340 Canadian researchers

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CCNA Goals and OBJECTIVESStrengthen and synergize Canadian innovative and collaborative researchBecome Canadian hub for leading and participating in international collaborationsReinforce the international positioning, competitiveness and impact of Canadian researchImpact the quality of life and services for those living with neurodegenerative diseases and their caregivers46CCNA THemes47

Theme 2 Leads: Dr. Sandra Black Dr. Mario Masellis

Team 11: Leads: Dr. Nathan Herrmann Dr. Krista Lanctot Dr. Dallas Seitz $793,000/5 yearsTEAM 11: Prevention and Treatment of Neuropsychiatric Symptoms of Dementia in LTCGoals: Establish a network of researchers and clinicians focussed on NPS is LTCDevelop a research network of LTC across Canada 30 facilities in total representing all of CanadaConduct research studies evaluating strategies to treat and prevent NPS in LTC

48CARESS Sites

BCABSKMBONQCNLNBNSPEIInstitut Universitaire deGeriatrie de MontrealDonald Berman MaimonidesGeriatric CentreSte. Annes Hospital VeteransAffairs CanadaCSSS Jeanne-Mance

Sunnybrook Veterans CentreChartwell Wynfield Long Term CareRekai CentreWellesley Central PlaceWest Park Long Term CareMcCormick HomeMcGarrell PlaceRocmaura Inc.Bow View ManorNorthwood BedfordIncorporated

LTC SITES: CCNA Team 11Overlander Residential CareRidgeview Lodge

Windsor Elms Village for Continuing Care SocietyProvidence ManorCentre des services de sant et sociaux (CSSS) de la Vieille Capitale

-Rekai and Wellesley still have to be confirmed by the new director at each of those LTCs (identified by Dr. Fischer; she has already sent an email to the new directors inviting them to participate)-Dr. Thorpe is still waiting to hear back from 2 LTCs in SK 49CARESS Sites

BCABSKMBONQCNLNBNSPEIDr. Marie-Andree BruneauDr. Anne BourbonnaisDr. Machelle WilcheskyDr. Ovidui Lungu

Dr. Nathan HerrmannDr. Krista LanctotDr. Arlene AstellDr. Corinne FischerDr. Simon DaviesDr. Bruce PollockDr. Tarek RajjiDr. Amer BurhanDr. Lisa Van BusselDr. Sarah ThompsonDr. Barry ClarkeDr. Keri-Leigh Cassidy

LTC SITES: CCNA Team 11Dr. Zahinoor IsmailDr. Colleen MaxwellDr. Barry ClarkeDr. Keri-Leigh CassidyDr. Dallas SeitzDr. Carol WardDr. Edeltraut KrogerDr. Philippe LandrevilleDr. Philippe Voyer

CCNA ProjectsSurvey of LTC facilities, resources and current practicesValidation of routinely collected LTC dataClinical Studies:Optimizing Prescribing of Antipsychotics in LTC (OPAL)Mobile Technology Based Intervention for NPS in LTCRandomized controlled trial of cholinesterase inhibitor discontinuation51ConclusionsNon-pharmacological interventions have increasing evidence to support their useThe risks and benefits of starting and continuation of medications for NPS need to be carefully considered for on an individual basisThe CCNA will provide Canada with a unique opportunity to strengthen research capacity into NPS in LTC across Canada52QUestionsDr. Dallas SeitzEmail: seitzd@providencecare.ca

53RESOURCESMobile Applications:

IA-ADAPT University of Iowa: Improving Antipsychotic Appropriateness in Dementiawww.healthcare.uiowa.edu/igec/iaadapt

BPSD GuideBehavior Management A Guide to Good Practice, Managing Behavioral and Psychological Symptoms of Dementia (BPSD)54

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Patient Resources

www.choosingwiselycanada.orgResourcesCanadian Coalition for Seniors Mental Healthwww.ccsmh.ca

Clinician Pocket Card:Tool on the Pharmacological Treatment of Behavioral Symptoms of Dementia in Long-Term Carewww.cavershambooksellers.com56

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