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TAREK K. RAJJI, MD, FRCPC CHIEF, GERIATRIC PSYCHIATRY DIVISION CENTRE FOR ADDICTION AND MENTAL HEALTH ASSOCIATE PROFESSOR OF PSYCHIATRY UNIVERSITY OF TORONTO.

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Presentation on theme: "TAREK K. RAJJI, MD, FRCPC CHIEF, GERIATRIC PSYCHIATRY DIVISION CENTRE FOR ADDICTION AND MENTAL HEALTH ASSOCIATE PROFESSOR OF PSYCHIATRY UNIVERSITY OF TORONTO."— Presentation transcript:

1 TAREK K. RAJJI, MD, FRCPC CHIEF, GERIATRIC PSYCHIATRY DIVISION CENTRE FOR ADDICTION AND MENTAL HEALTH ASSOCIATE PROFESSOR OF PSYCHIATRY UNIVERSITY OF TORONTO Management of Agitation and Aggression Associated with Alzheimer’s Disease

2 Disclosures None

3

4 “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, Auguste Deter

5 “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

6 “APATHY” Withdrawn Lack of interest Amotivation “DEPRESSION” Sad Tearful Hopeless Low self-esteem Anxiety Guilt “AGGRESSION” Aggressive resistance Physical aggression Verbal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

7 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%)

8 Behavioral and Psychological Symptoms of Dementia Peak during moderate/moderately-severe stages (Reisberg et al., 1987) Agitation/aggression, apathy may continue to increase (Mega et al., 1996) Affective symptoms are more common early in the illness (Rubin et al., 1988)

9 Agitation/Aggression Incidence: 50% over course of illness (Tariot & Blazina, 1994) Jost & Grossberg, 1996

10 Cummings, 2003

11 Aggression & Agitation in Dementia “Inappropriate verbal, vocal or motor activity not explained by apparent needs or confusion” (Cohen- Mansfield, 1986) Aggression Agitation Physical Verbal Physical

12 Agitation in Dementia: Subtypes Cohen-Mansfield,J International Psychogeriatrics. 8(3):309.

13 Treatment Algorithms: Evidence  Algorithm use in clinical practice associated with:  Improved quality of care  Enhanced patient outcomes  Reduced health care costs Adli. M et al Biological Psychiatry

14 Treatment Algorithms: Evidence StudyyearNInterventionTAUResults IMPACT (late-life depression) 2002Int-906 Cont Depression Algorithm -Case manager supervision of primary care -Primary care practitioner - available mental health services Significant: -Decline in depressive sxs, - Decreased symptom severity -increased care satisfaction PROSPECT (late life depression) 2004Int-320 Cont Depression algorithm -Case manager supervision of primary care -primary care with education Significant reduction in: -remission time, -sx severity, -suicidal ideation TMAP (Texas Medication Algorithm Project) (depression) 2004Int-175 Cont 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) 2009Int-74 Cont-74 -inpatient care with adherence to medication algorithm -inpatient mental health care Significant: decreased time to remission, fewer medication changes in remitters.

15 Why do we need a pathway? Better Outcomes More Access More Data New Approaches Better Knowledge

16 Pathway Assessment & Medications Discontinuation Cognitive Enhancers (AChEI, Memantine) Pharmacological Non- Pharmacological

17 Zaraa, 2003

18 Physical Factors Delirium - Dipstix urine, check temperature and bloods e.g. FBC, U&E, LFT, TFT, ESR, CRP, Glucose, Vitamin B12, folate and ferritin levels Dehydration – check above blood levels; especially U&E. Commence on fluid balance chart Pain – complete appropriate pain assessment tool e.g. Abbey Scale Hunger – monitor and complete fluid and diet charts Constipation – monitor bowel habits Tiredness – chart sleep pattern Medication – side effects Medication withdrawals – e.g. benzodiazepines, opiates Sensory Impairment – sight &/or hearing deficit - refer to sensory impairment service for assessment and advice (where applicable) Hypoxia – cyanosis, laboured breathing NHS Forth Valley

19 Psychological Factors Depression – observe for any mood or behavioural changes. Complete appropriate assessment tool Hallucinations – more commonly seeing&/or hearing things. NB exclude delirium Delusions – more commonly paranoia &/or suspiciousness. NB exclude delirium Sundowning - increased agitation and activity occurring in the late afternoon/early evening NHS Forth Valley

20 Environmental Factors Noise levels – over stimulation/elevated noise levels can be antagonistic Lack of social stimulation Inappropriate music – ensure age related and appropriate to the client group Environment/layout  Is it conducive to the specific client group?  Could it potentially increase confusion and disorientation in people suffering from cognitive impairment? NHS Forth Valley

21 Attending PhysicianDIAGNOSTIC WORK-UP: HISTORYYESYES NONO Name: Sign: Date: (dd/mm/yyyy) Agitation or aggression is present Clinically suspected to be secondary to Alzheimer’s or mixed Alzheimer’s + vascular dementia History consistent with Alzheimer’s or mixed Alzheimer’s vascular dementia Attending PhysicianDECISION TO MOVE FORWARDY ES NONO Name: Sign: Date: (dd/mm/yyyy) Delirium or other causative medication/medical condition identified? Presentation more consistent with non-Alzheimer’s Dementia? If “Yes” exit pathway Is the Agitation and Aggression: Severe? Causing distress to the patient? Or OTHERS? Preventing or interfering with providing necessary care to the patient? Posing a risk to the patient or to others? If “Yes” to ANY questions, proceed with pathway, otherwise exit pathway HospitalistDIAGNOSTIC WORK-UP: PHYSICAL EXAM INVESTIGATIONYESYES NONO Name: Sign: Date: (dd/mm/yyyy) Basic investigation done to rule out other medical causes of cognitive impairment or agitation Guidelines: vital signs, height, weight, waist circumference, CBC with differential, renal function, liver panel, metabolic/endocrine function, B12, urine analysis, urine C&S, lipid profile, fasting glucose +/- HbA1C, micro albuminuria, extended electrolytes, Delirium screening tool (optional) Examples: Confusion Assessment Method, Delirium Symptom Review, Delirium Rating Scale Addition investigations performed as indicated (optional) List additional investigations: ____________________________________________________________________________________ ______

22 Research Fellow Name Sign: Date: (dd/mm/yyyy) Cohen-Mansfield Agitation Inventory (CMAI) Initial Score: _________________________ Comments: ________________________________ ________________ ________________________________ ________________ YE S NO Neuropsychiatric Inventory (NPI) Initial Score: _________________________ Comments: ___________________________________ _____________ ___________________________________ _____________ Montreal Cognitive Assessment (MOCA) Initial Score: _________________________ Comments : ___________________________________ _____________ ___________________________________ _____________ Alzheimer’s disease assessment scale – cognitive subscale (ADAS-cog) Initial Score: _________________________ Comments : ___________________________________ _____________ ___________________________________ _____________ Attending Physician Name Sign: Date: (dd/mm/yyyy) Clinical Global Impression Scale (CGI) Initial Score: _________________________ Comments : ________________________________ ________________ ________________________________ ________________ YE S NO Abnormal Involuntary Movement Scale (AIMS) Initial Score: _________________________ Comments : ___________________________________ _____________ ___________________________________ _____________ Simpson-Angus Scale (SAS) Initial Score: _________________________ Comments : ___________________________________ _____________ ___________________________________ _____________ Barnes Akathisia Scale (BAS) Initial Score: _________________________ Comments: ___________________________________ _____________ ___________________________________ _____________

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24 HospitalistCARDIAC AND METABOLIC ASSESSMENTYESNO Name Sign: Date: (dd/mm/yyyy) CBC, ECG, Creatinine/BUN, Blood Sugar, Lipid Profile Comments: ___________________________________________________________________________________ _________ ___________________________________________________________________________________ _________ Assigned NursePAIN ASSESSMENT AND MANAGEMENTYESNO Name: Sign: Date: (dd/mm/yyyy) Pain Assessment and Management Conducted For example: Brief Pain Inventory (BPI) for verbal patients Checklist of Non-Verbal Pain Indicators (CNPI) for non-verbal patients Occupational Therapist FUNCTIONAL ASSESSMENTYESNO Name: Sign: Date: (dd/mm/yyyy) Functional Assessment Staging (FAST) Comments: ____________________________________________________________________________________ ________ ____________________________________________________________________________________ ________

25 Pathway Assessment & Medications Discontinuation Cognitive Enhancers (AChEI, Memantine) Pharmacological Non- Pharmacological

26 Non-Pharmacological Interventions Consent Caregiver education and support Enhance communication with the patient Ensure safe environment Increase or decrease stimulation in the environment

27 Non-Pharmacological Interventions For all BPSD: 31 studies that used RCT-design (1-52 weeks): Reminiscence  mild to moderate depression (7/8) Pleasant activities with or without social interactions  agitation (4/4), depression (2/2) Personalized music  agitation (4/7) Exercise  depression (2/5)

28 Non-Pharmacological Interventions Allied Health Professional NON-PHARMACOLOGICAL INTERVENTIONS IDENTIFIED INITIALLY AS MOST APPROPRIATE* Please check discipline: Occupational Therapist Recreation Therapist Social Worker Primary Nurse Name: Sign: Date: Social Contact Pet therapy One-to-one visit Other:_________ ______ Sensory Enhancement/ Relaxation Hand massage Individualized Music Individualized art Sensory modulation Other:_________ ______ Purposeful Activity Helping tasks / Volunteer role Inclusion in group programs of identified interest Access to outdoors Other:__________ _____ Physical Activity Exercise group Indoor/outdoor walks Individual exercise program Other:__________ _____

29 Multisensory Snoezelen System

30 Paro Therapeutic Robot

31 Pharmacological Interventions Risperidone Aripiprazole Citalopram Carbamazepine Gabapentin Prazosin ECT Quetiepine 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

32 Drugs commonly used for agitation Antipsychotics Antidepressants  SSRIs, trazodone Cognitive enhancers  Cholinesterase inhibitors, memantine Mood stabilizers and Anticonvulsants  carbamazepine  valproic acid  gabapentin  oxcarbazapine  topiramate  lamotrigine  lithium

33 Antipsychotics TreatmentTrials conductedEvidence Typicals11 randomized, placebo- controlled trials; duration bw 4-16 wks Modest advantage over placebo Atypicals18 placebo-controlled trials (6-12 wks) 3 trials 6-12 months) Best option for short- term (6-12 wks) 1. Schneider L. Am J Geriatr Psych 2006:14(3) Ceitz et al. Cochrane Review, Ballard & Corbett. 2013:25(3)

34 Antipsychotics Mainstay of psychopharmacological treatment  Up to 40% of all dementia patients prescribed antipsychotics 1 Atypicals vs. typicals: perceived safety advantage In patients with dementia, atypicals increase:  risk of death (OR= )  cerebrovascular adverse events (OR=2.7)  rate of cognitive decline 1. Schneider L. Am J Geriatr Psych 2006:14(3) Ballard & Corbet. Current Opin Pysych. 2013:226(3) Hermann & Lanctôt. Drug Safety. 2006:29(10)

35 Atypical Antipsychotics Antipsychotic# trialsBottom Line Risperidone5 RCTs Provides best evidence for treating aggression Modest but significant improvement vs. placebo Biggest effect size: 2 mg daily Olanzapine5 RCTs (fixed dose 1-15 mg daily, 6-10 weeks of treatment) Conflicting evidence More adverse events of hostility, abnormal gait, somnolence Not associated with overall efficacy Schneider L. Am J Geriatr Psych 2006:14(3) Ballard et al. Cochrane Review

36 Atypical Antipsychotics Antipsychotic# trialsBottom Line Aripiprazole2 RCTs Benefits similar to risperidone Caveat: studied in context of psychosis Quetiapine3 RCTs significantly > cognitive decline ineffective in treating agitation Schneider L. Am J Geriatr Psych 2006:14(3) Ballard et al. Cochrane Review. 2012

37 Antidepressants SSRI’s# trialsMain findings Meta-analysis of 9 trials, n=692; five studies compared SSRIs to placebo, only two studies included in meta- analysis 1. Limited trials addressing aggression or agitation Citalopram vs. placebo: ↓ agitation and aggression Citalopram vs. risperidone: improved effect on agitation, better tolerated Some benefit shown for sertraline & citalopram for overall BPSD vs placebo; no statistically significant difference vs. antipsychotics. May have role in treating aggression and agitation Better tolerated than antipsychotics Indicated if depression present 1. Ballard & Corbegtt. Current Opin Psychiatry (3) Pollock, BG, Mulsant, BH, Rosen J et al. Am J Pscychiatry 2002; 159: Pollock, Mulsant, Rosen et al. Am J Geriatr Psychiatry 2007;15:

38 Antidepressants 1.Martinon et al., Cochrane Review, Henry et al. Am J Alz Dis & Other Dementias 2011:26(3) Trazodone studies# placebo-controlled RCTs Bottom line Martinon et al.2 placebo-controlled RCT’s (n=104; dosage mg, up to six weeks) No significant benefit vs. placebo Henry et. al.3 original trials 1 trial vs. placebo) 2 trials vs. haloperidol trazodone > haldol trazodone = haldol=placebo

39 Cognitive Enhancers Rodda et al. Int. Pyschoger 2009:21:5; Cognitive enhancer#P-C RCTs includedOutcome on agitation donepezil92 positive 1 trial positive for continuing vs. placebo after initial open label treatment phase galantamine31 positive rivastigmine20 positive

40 Anticonvulsants & mood stabilizers Drug Overall findings for agitation & aggression Bottom Line Carbamazapine- Few clinical trials (1 meta-analysis, 3 clinical trials) - Conflicting evidence - ↑ risk drug-drug interactions, poorly tolerated in long-term use Promising for global BPSD, esp. agitation & aggression (dose mg over 6-8 wks) Not recommended for routine treatment of agitation Valproate-Meta-analysis: unacceptable rate of adverse effects (esp. sedation) > 15mg/kg/d -3 RCTs: no improvement in aggression; 1 RCT: worsened hostility; Higher quality studies including RCTs and meta-analyses do not support use for agitation; may worsen aggression Yi-Chun & Ouyang. Kaoh J of Med Sci (2012): 28,

41 DrugOverall findings for agitation & aggression Bottom line GabapentinNo meta-analysis or RCTs Data limited (11 case reports, 3 case series, 1 retrospective chart review) well tolerated, some effectiveness for overall BPSD, (mean dose 900 mg daily) - dearth of data OxcarbazepineOne RCT on agitation & aggression Negative results TopiramateLack of RCTsAdverse effect on cognition Use not supported in BPSD LamotrigineCase series, case reports, no RCTs using objective measures May be effective Adverse effects: rash, somnolence, tremor LithiumCase series, most > 20 y o, lack of valid instruments Conflicting results Yi-Chun & Ouyang. Kaoh J of Med Sci (2012): 28,

42 Anticonvulsants & mood stabilizers Summary: CBZ most promising mood stabilizer for patients with aggression, hostility and (possibly) agitation  Also effective for global BPSD  Effective dose range: mg daily over 6-8 weeks

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44 Electro-Convulsive Therapy (ECT) Case series, 4 patients, failed psychotropics  2 to 4 ECT sessions  meaningful reduction in symptoms for 3 to 12 months (Grant et al. 2001) Case series, 3 patients with manic-like symptoms, failed psychotropics  1-2 weeks of ECT followed improvement in mania and agitation (McDonald et al. 2001) 92 year-old female, vascular dementia, failed haloperidol  2 ECT sessions  BPSD resolves for 3 months (Katagai et al. 2007)

45 Electro-Convulsive Therapy (ECT) 16 hospitalized patients (mean age = 66.6, SD = 8.3) with mild to severe dementia.  12 patients  bilateral ECT  3 patients  right unilateral ECT  bilateral ECT  1 patient  only right unilateral ECT On average, 9 treatments (range: 2 to 15) All patients improving except for one Ujkaj et al. 2012

46 Pathway of Care Assessment & Medications Discontinuation Cognitive Enhancers (AChEI, Memantine) Pharmacological Non- Pharmacological Risperidone Aripiprazole Citalopram Carbamazepine Gabapentin Prazosin ECT Quetiepine

47 Dr. Amer Burhan Dr. Simon Davies Dr. Donna Kim Dr. Benoit Mulsant Dr. Bruce Pollock Dr. Vincent Woo Ms. Rong Ting Dr. Sawsan Kalache Ms. Saima Aiwan Mr. Christopher Uranis

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