Symptoms In Dementia TAREK K. RAJJI, M.D. C A N A D A R E S E A R C - - PowerPoint PPT Presentation

TAREK K. RAJJI, M.D.

C A N A D A R E S E A R C H C H A I R

• I N N E U R O S T I M U L AT I O N F O R C O G N I T I V E D I S O R D E R S

P R O F E S S O R O F P S Y C H I AT R Y, U N I V E R S I T Y O F T O R O N T O C H I E F O F A D U L T N E U R O D E V E L O P M E N T A N D G E R I AT R I C P S Y C H I AT R Y D E P U T Y P H Y S I C I A N - I N - C H I E F F O R R E S E A R C H C E N T R E F O R A D D I C T I O N A N D M E N T A L H E A L T H

American University of Beirut, July 1, 2019

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Standardizing Care For Neuropsychiatric Symptoms In Dementia

Disclosure Statement

• The presenter has no financial interest/arrangement or affiliation

with any organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

• Off-label medication use will be discussed.

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Objectives

• 1. Describe the evidence and rationale for an integrated care

pathway (ICP) for management of neuropsychiatric symptoms

• f dementia.
• 2. Discuss the key components of the ICP and its

implementation.

• 3. Describe the design of a new randomized controlled trial to

compare the ICP with usual care (the StaN study).

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http://www.alz.co.uk/sites/default/files/pdfs/world-alzheimer-report-2015-executive-summary-english.pdf

“One of the first disease symptoms of a 51-year-old woman was a strong feeling of jealousy towards her husband. Very soon she showed rapidly increasing memory impairments; … thought that people were out to kill her, then she would start to scream loudly.”

• Dr. A. Alzheimer, 1906.

Auguste Deter

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“From time to time she was completely delirious, dragging her blankets and sheets to and fro, calling for her husband and daughter, and seeming to have auditory hallucinations. Often she would scream for hours and hours in a horrible voice.”

• Dr. A. Alzheimer, 1906

Auguste Deter

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“APATHY” Withdrawn Lack of interest Amotivation “DEPRESSION” Sad Tearful Hopeless Low self-esteem Anxiety Guilt “AGGRESSION” Aggressive resistance Physical aggression Verbal aggression “PSYCHOSIS” Hallucinations Delusions Misidentifications “MOTOR HYPERACTIVITY” Increased walking Walking aimlessly Moving objects Trailing McShane, 2000

Behavioral and Psychological Symptoms of Dementia

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• 90% of patients during the course of their illness (Tariot, 1999)
• 60-90% of patients with dementia suffer from BPSD (Lyketsos et al., 2002)
• Agitation & Aggression (75%)
• Wandering (60%)
• Depression (50%)
• Psychosis (30%)
• Screaming and violence (20%)

(Jeste DV, Finkel SI, 2000)

Behavioral and Psychological Symptoms of Dementia

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• Agitation/aggression peak during moderate/moderately-severe

stages (Reisberg et al., 1987)

• Apathy may continue to increase (Mega et al., 1996)
• Affective symptoms are more common early in the illness

(Rubin et al., 1988)

Behavioral and Psychological Symptoms of Dementia

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Cummings, 2003

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Management Guidelines

• Position Statement of the American Association for Geriatric

Psychiatry Regarding Principles of Care for Patients With Dementia Resulting From Alzheimer Disease, Lyketsos et al., American Journal of Geriatric Psychiatry, (2006). 14: 561-72

• Guidelines: Managing Behaviour Problems in Patients with

Dementia ( 2015) NHS Foundation Trust

• Guideline watch: Practice guideline for the treatment of patients

with Alzheimer’s disease and other dementias. Rabins et al. (2014)

• CCCDT4 Guidelines (Dec 2012)

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Dementia prevention, intervention, and care. Gill Livingston et. al. The Lancet July 2017

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Vasudev et al. 2015

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Health Quality Ontario, 2015

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Algorithmic Treatment

• Faster symptom control
• Decreased length of stay
• Lower rates of polypharmacy
• Higher patient and care giver satisfaction
• Reduced health care costs

Katon et al. 1995, Trivedi et al. 2004, Adli. M et al. 2006, Mulsant et. al. 2001, 2014

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Treatment Algorithms: Evidence

Study year N Intervention TAU Results

IMPACT (late-life depression) 2002 Int-906 Cont-895

• Depression Algorithm
• Case manager supervision
• f primary care
• Primary care

practitioner -available mental health services Significant:

• Decline in depressive sxs,
• Decreased symptom severity
• increased care satisfaction

PROSPECT (late life depression) 2004 Int-320 Cont-276

• Depression algorithm
• Case manager supervision
• f primary care
• primary care with

education Significant reduction in:

• remission time,
• sx severity,
• suicidal ideation

TMAP (Texas Medication Algorithm Project) (depression) 2004 Int-175 Cont-175

• Depression algorithm
• psychoeducation
• biweekly expert

consultation

• Outpatient care

without algorithm use Significant : improvement in symptom severity and function at 1 year GAP (German Algorithm Project ) (depression) 2009 Int-74 Cont-74

• inpatient care with

adherence to medication algorithm

• inpatient mental

health care Significant: decreased time to remission, fewer medication changes in remitters.

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Integrated Care Pathway for Agitation in Dementia

• Standardized medical work-up
• Non-pharmacological interventions, including a clean-up phase
• Algorithmic approach for medications
• Measurement based decisions

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Assessments

Baseline End of Clean-up (Week 1) End of non- pharmacological interventions (Week 3) Follow up during pharmacological phase (Every two weeks from week 4 -12) Additional Mid-point Follow up (Week 8) Exit (End of Week 12)

BPSD symptoms and cognitive assessments

Neuropsychiatric Inventory (NPI-C)

    

CGI-Severity



CGIC

   

CMAI

    

MOCA and SCIRS (if MOCA score is less than 5)

  

Dementia-FAST

   Motor Assessments

AIMS

  

SAS

  

BAS

   Pain assessment

PAINAD

   Caregiver/ Quality of Life Assessments

ZBI

  

ADRQL

  

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Non-Pharmacological Interventions for Agitation

• 33 RCTs were included
• Evidence found for
• Person Centered Care
• Communication Skills training
• Dementia Care Mapping
• Personalized music
• Sensory therapy
• Other reviews and met analyses with different results but general

consensus about use of personalized, sensory and care giver interventions.

Livingstone et al. Br J Psychiatry. 2014 Dec;205(6):436-42 Abraha I et al. BMJ Open 2017

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Non-Pharmacological Interventions

Health Professional NON-PHARMACOLOGICAL INTERVENTIONS IDENTIFIED INITIALLY AS MOST APPROPRIATE Occupational Therapist Recreation Therapist Social Worker Assigned Nurse Social Contact: Pet therapy, one-on-one visits Sensory Enhancement/Relaxation: Hand massage, individualized music, individualized art, sensory modulation, Snoezelen Purposeful Activity: Helping tasks/volunteer role, inclusion in group programs, access to outdoors Physical Activity: Exercise - group and individual, indoor/outdoor walks Neurocognitive Intervention: Paro, tablet computer, gaming console

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BASELINE ASSESSMENTS & DRUG CLEAN UP RISPERIDONE QUETIAPINE CARBAMAZEPINE CITALOPRAM GABAPENTIN PRAZOSIN COMBINATION or E.C.T. ARIPIPRAZOLE

Medication Algorithm

Davies et. al. J Psychopharmacol. 2018

For partial responders:

• 1. Extend the trial
• 2. Increase the dose
• 3. Augment with another agent that showed

also partial response PRNs:

• 1. Trazodone
• 2. Lorazepam

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Enrolled (N= 62) Successfully Completed (N = 54) No medications (N = 9, 16%) Step 1 (N = 23, 43%) Step 2 (N =14, 26%) Step 3 (N = 5, 9%) ECT (N = 1, 2%) Polypharmacy (N = 2, 4%) Active (N = 3) Premature Exit (N = 5)

• 3 Medical discharge
• 1 Lewy Body
• 1 Deceased

Overall Results

Based on literature (Vasudev et. al, 2015*) , 50% of similar patients were treated with 2 or more medications in LTCFs in 2013, an increase from 42% in 2004. Our results show that 4% needed to be 2 or more medications.

*http://www.ncbi.nlm.nih.gov/pubmed/26525997 85% : Step 2 or before

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Assessing the outcomes and comparison to usual care

ICP 2013

Dementia ICP Group

2016 2010 Dementia NON ICP Group (Usual Care) Non Dementia Group 2 (Control Group 2) Non Dementia Group 1 (Control group 1)

Group Characteristics

Dementia NON ICP Group (2010-2013) Dementia ICP Group (2013-2016) Control Group 1 (2010-2013) Control Group 2 (2013-2016)

Number (Females)

33 (14) 37 (23) 22 (9) 36 (21)

Age, Mean (SD)

76.7 (9.2) 77.1 (9.8) 68.3 (4.5) 69.1 (8.6)

Number of Psychotropic Medications at Admission Mean (SD)

1.7 (1.3) 1.1 (1.1) 1.8 (1.3) 1.9 (1.1)

Active Length of Stay

Dementia NON ICP group = 99.3 (107.0) days Dementia ICP group = 57.3 (36.3) days Control Group 1 = 34.7 (34.9) days Control Group 2 = 41.4 ( 38.7) days Univariate Multifactor ANOVA Group*Time Interaction F1, 126 = 4. 46, p = 0.037

Psychotropic Medications at Discharge

Mean (SD) Number of Psychotropics: Dementia NON ICP Group = 1.7 (1.1) Dementia ICP Group = 1.1 (0.5) Control Group 1 = 1.9 (1.2) Control Group 2 = 2.2 (1.0) Univariate Multifactor ANOVA Group*Time Interaction F1, 127 = 8.29, p = 0.003

Summary

• It is feasible to use an algorithmic approach (ICP) to treat

agitation/aggression in dementia.

• The ICP is effective in treating agitation/aggression in

dementia.

• ICP may treat agitation with a shorter length of stay and lesser

number of psychotropic medications.

• Future studies should compare ICP with usual care in a

Randomized Controlled Design.

Standardizing Care For Neuropsychiatric Symptoms and Quality of Life in Dementia “StaN STUDY”

http://atlantislsc.com

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Objectives and Hypotheses

Primary Objective 1: To assess the efficacy of the ICP in patients with AD-AA. Primary Hypothesis 1a: Compared to TAU, the ICP will result in significantly lower CMAI- frequency scores at the end of the trial (12 weeks). Exploratory Hypothesis 1b: Compared to TAU, the ICP will result in significantly lower CMAI- frequency scores at 3 and 8 weeks. Exploratory Hypothesis 1c: Compared to TAU, the ICP will result in a shorter time to response in AD-AA as defined by a CGIC < 3. Exploratory Hypothesis 1d: Compared to TAU, the ICP will result in a significantly lower rate of falls. Exploratory Hypothesis 1e: Compared to TAU, the ICP will result in a significantly lower agitation/aggression and global burden of neuropsychiatric symptoms as assessed by NPI-C at 3 weeks (the end of standalone non-pharmacological interventions phase), 8 weeks and 12 weeks (end of the trial).

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Objectives and Hypotheses

Primary Objective 2: To assess the impact of the ICP on inappropriate use of medications in patients with AD-AA. Primary Hypothesis 2: Compared to TAU, the ICP will result in a significantly lower proportion of participants on polypharmacy for AD-AA. Exploratory Objective 3: To assess the impact of ICP on caregiver burden and health-related quality of life. Exploratory Hypothesis 3a: Compared to TAU, the ICP will result in lower caregiver scores on Zarit Burden Interview. Exploratory Hypothesis 3b: Compared to TAU, the ICP will result in improved quality of life as reflected by higher scores on the Alzheimer’s Disease Related Quality of Life scale (ADRQL). Exploratory Objective 4: To undertake a cost-effectiveness analysis of the ICP for patients with AD-AA during the 3-month (12 week) RCT and the 6-month naturalistic follow-up. Exploratory Hypothesis 4: Compared to TAU, the ICP will be more cost-effective.

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Informed Consent, Eligibility Baseline Assessments: NPI-C,CGI-Severity, CMAI, MOCA and SCIRS, Dementia-FAST, AIMS SAS, BAS, PAINAD, ADRQL, ZBI INTEGRATED CARE PATHWAY (ICP) RANDOMIZATION TREATMENT AS USUAL (TAU) Cleanup and non-pharmacological interventions (1 week) Week 1 of the trial Standalone: Non-pharmacological interventions (2 weeks) Week 2 and 3 of the trial Pharmacological Interventions Phase (1-9 weeks) Week 4-12 of the trial End of RCT (12 weeks) NPI-C, CGIC, CMAI, NPI-C, CGIC, CMAI, MOCA and SCIRS, Dementia-FAST, AIMS, SAS, BAS, PAINAD, ADRQL, ZBI CGIC completed every two weeks until the end of the RCT, CMAI and NPI-C will be completed at week 8 Exit Assessments: NPI-C, CGIC, CMAI, MOCA and SCIRS, Dementia-FAST, AIMS SAS, BAS, PAINAD, ADRQL, ZBI End of RCT (12 weeks) Non-pharmacological Interventions Week 1 Week 3 Week 4-12 Post Cleanup

220 Participants

7 sites Inpatient: 4 LTCF: 3

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Acknowledgments

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Co-PI: Dr. Sanjeev Kumar Co-Investigators (alphabetical):

• Dr. Amer Burhan - Western University London
• Dr. Sarah Colman - CAMH
• Dr. Simon Davies - CAMH
• Dr. Philip Gerretsen - CAMH
• Dr. Ariel Graff – CAMH
• Dr. Zahinoor Ismail - University of Calgary
• Dr. Paul Kurdyak – CAMH
• Dr. Benoit Mulsant - University of Toronto
• Dr. Vasavan Nair - Douglas Hospital Research Centre
• Dr. Claire de Oliveira – CAMH
• Dr. Bruce Pollock - CAMH
• Dr. Soham Rej – McGill University
• Dr. David Streiner - McMaster University

Collaborators (alphabetical):

• Dr. Steve Crawford - McCormick Care Group, London
• Dr. Peter Derkach- Ukrainian Canadian Care Centre, Toronto.
• Dr. Donna Kim- CAMH
• Ms. Linda Krisman - Patient Family Representative
• Dr. Lillian Lourenco– CAMH
• Dr. Rola Moghabghab - CAMH
• Ms. Jyll Simmons- CAMH
• Dr. Jane Summers- CAMH

ABC Checklist

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Example of a Structured Algorithm

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Below is an example of a daily structured algorithm of behavioural interventions that will be followed throughout the week during working days and will be customized as per needs of the participant. The same general principles will be followed to maintain homogeneity across sites.

1. Review of previous 24 hrs agitation episodes with treatment team on ABC framework (complete ABC checklist for each incident of significant agitation/aggression) 2. Review of Sleep/feeding/bowel movement for the last 24 hours and identification of challenges 3. 30 min 1:1 interaction and person-centered activity based on above review. 4. 30 min light physical activity /supervised walking guided by patient’s physical status 5. 30 min music/art therapy based on personal choice 6. One hour purposeful activity/use of neurocognitive technology such as PARO (robotic seal)/ Hasbro cats/ other stuffed toys/watching videos/playing games guided by personal choice. Pick only one activity for one person for the given week. 7. 5 min of brief mindfulness-based activity

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CAMH and Late Life 1,400 unique

• utpatients (60+)

48 inpatients beds (65+) Multiple Specialty Clinics 30+ Long-T erm Care Facilities 18 geriatric psychiatrists 1 behavioral neurologist 1 neuropsychologist 1 hospitalist Research: $18M

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Agitation in cognitive disorders: International psychogeriatric Association provisional consensus clinical and research

• A. The patient meets criteria for a cognitive impairment or dementia syndrome
• B. The patient exhibits at least one of the following behaviors that are associated with observed or inferred

evidence of emotional distress. (minimum of two weeks’ and represents a change from the patient’s usual behavior.) (a) Excessive motor activity (b) Verbal aggression (c) Physical aggression

• C. Behaviors are severe enough to produce excess disability,

(a) Significant impairment in interpersonal relationships. (b) Significant impairment in other aspects of social functioning. (c) Significant impairment in ability to perform or participate in activities.

• D. not attributable solely to another psychiatric disorder, suboptimal care conditions, medical condition, or the

physiological effects of a substance.

Cummings et. al. International Psychogeriatrics (2015)

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Health Quality Ontario, 2015

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CAMH Integrated care pathways include:

Pharmacological Interventions (Medication Algorithms/Titration Schedules) Non- Pharmacological Interventions (Psychosocial / Behavioural interventions) Clinical Team Intervention (High Performing Teams / Inter-professional Collaboration) Measurement- based care

CORE Enablers

Collaboration Evaluation Outcome Oriented

Sustainability Evidence Base Efficient Processes Effective Team

• Change Management
• Knowledge Translation
• Project Management

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Core principles of an ICP

Adapted from Alberta Health Services

“A Clinical Pathway is a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to help a patient with a specific condition or set of symptoms move progressively through a clinical experience to positive outcomes”. Middleton S Barnett J & Reeves D (2001)

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ICP Structure

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BRAIN CANADA GRANT Accreditation Canada Leading Practice Accreditation Canada Leading Practice

Current Integrated Care Pathways Initiatives

CAMH

Dementia (Agitation and Aggression) Depression and Alcoholism Bipolar Depression Early Psychosis (Slaight Centre) Late Life Schizophrenia Major Depressive Disorder Alcohol Use Disorder

External

Community Hospitals Long Term Care Facilities DA VINCI (ARTIC PROJECT) Academic Health Science Centres Community Hospitals Primary Care Settings CABHI GRANT ARTIC GRANT CIHR SPOR GRANT

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HQO Quality Standards: Behavioural Symptoms of Dementia

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Lessons learned

• Executive sponsorship at both the host site and at participating
• rganizations is pivotal to success
• Substantive efforts are required from core team at the host site
• The culture shift of introducing a pathway ideology is substantial and,

accordingly, implementation is not always rapid

• Implementation of a standardized pathway into a non-standardized

sector requires flexibility and adaptability at every turn

• Commitment from the frontline clinicians is necessary in order for the

change in practice to happen

• Importance of having good data quality infrastructure for continuous

improvement

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Antipsychotics

Trials conducted Summary Typical Antipsychotics Multiple randomized, placebo- controlled trials; duration 4-16 week duration Modest advantage over placebo Atypical Antipsychotics Multiple placebo-controlled trials (6-12 week duration) some trials 6-12 months, Discontinuation Trials Better than placebo, at least short- term (6-12 weeks)

Schnieder et al. Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210.. Ballard & Corbett. Curr Opin Psychiatry. 2013 May;26(3):252-9 Ballard C. et al. Nat Rev Neurosci. 2006 Jun;7(6):492-500. Devanand et. al. N Engl J Med 2012; 367:1497-1507

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Antidepressants

Studies Summary Meta-analysis of 9 trials, n=692; five studies compared SSRIs to placebo, only two studies included in meta-analysis. Citalopram vs. risperidone: improved effect on agitation, better tolerated CitAD Randomized Controlled Trial RCT level evidence for citalopram for Agitation. Better tolerated than antipsychotics but

• nset of action is slower.

Evidence less clear about other antidepressants due to quality of studies.

Ballard et al. Current Opin Psychiatry. 2013 26(3) 252-259. Pollock et al. Am J Pscychiatry 2002; 159:450-465. Pollock et al. Am J Geriatr Psychiatry 2007;15:942-952 Porsteinsson et al. JAMA. 2014 Feb 19; 311(7): 682–691.

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Cognitive Enhancers

Rodda et al. Int. Pyschoger 2009:21:5;813-24 Gauthier et al. Int J Geriatr Psychiatry. 2008 May;23(5):537-45. Fox et al. PLoS One. 2012;7(5):e35185. doi: 10.1371/journal.pone.0035185

Cognitive enhancer Summary Donepezil Only three studies showed reduction in NPI scores with AcheIs. Methodological issues, NPI secondary outcome in most of the studies. For Memantine pooled analyses from RCT’s for cognition showed benefit but then RCT with Agitation as primary outcome was negative. Galantamine Rivastigmine Memantine

Anticonvulsants

Drug Summary Carbamazapine RCT level evidence, promising for global BPSD and agitation & aggression ↑ risk of drug-drug interactions, poorly tolerated in long-term use Valproate Benefit in open label trials 3 RCT s: no improvement in aggression; 1 RCT : worsened hostility. Guidelines specifically recommend against using valproate.

Yeh et al. Kaoh J of Med Sci (2012): 28, 185-193. Herrmann et al. Dement Geriatr Cogn Disord. 2007;23(2):116-9 Tariot et al.The American Journal of Geriatric Psychiatry Volume 13, Issue 11, November 2005, Pages 942-949

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Drug Overall findings for agitation & aggression Summary Gabapentin Case series, retrospective chart review Well tolerated, some effectiveness for overall BPSD, Prazosin One RCT Positive Oxcarbazepine One RCT on agitation & aggression Negative results Topiramate Lack of RCTs Adverse effect on cognition Use not supported in BPSD Lamotrigine Case series, case reports, no RCTs using objective measures May be effective Adverse effects: rash, somnolence, tremor Lithium Case series Need more studies

Yeh et al. Kaoh J of Med Sci (2012): 28, 185-193. Kim et al. Drugs Aging. 2008;25(3):187-96. Wang et al. Am J Geriatr Psychiatry. 2009 Sep; 17(9): 744–751.

Other Medications

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Outcomes in the ICP Group

* * Paired t T est, p < 0.05

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Outcomes in the ICP Group

* Paired t test, p < 0.05

Length of stay

Independent Sample t test, p < 0.05

Psychotropic Medications at Discharge

Independent Sample t test, p < 0.05

Falls and Seclusion Episodes

Juror #8: No. I'm saying it's possible that the boy lost the knife and that someone else stabbed his father with a similar knife. It's possible.

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Objectives

• To Assess The Efficacy of ICP by Comparing Symptoms Burden

Between Entry and Exit from the ICP

• To Compare the ICP versus Usual Care
• Length of Treatment (Active Length of Stay)
• Psychotropic Medication Use
• Rates of Adverse events- Falls and Restraints/Seclusions

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