Management of Agitation and Aggression Associated with Alzheimer’s Disease

1. Management of Agitation and Aggression Associated with Alzheimer’s Disease Tarek K. Rajji, MD, FRCPC Chief, Geriatric Psychiatry Division Centre for Addiction and Mental Health Associate Professor of Psychiatry University of Toronto

2. Disclosures None

4. AugusteDeter “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.

5. AugusteDeter “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

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aimlessly Moving objects Trailing “AGGRESSION” Aggressive resistance Physical aggression Verbal aggression “APATHY” Withdrawn Lack of interest Amotivation “DEPRESSION” Sad Tearful Hopeless Low self-esteem Anxiety Guilt “PSYCHOSIS” Hallucinations Delusions Misidentifications McShane,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

7. Behavioral and Psychological Symptoms of Dementia • 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 (Reisberget 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. Jost & Grossberg, 1996 Agitation/Aggression Incidence: 50% over course of illness (Tariot & Blazina, 1994)

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 Verbal Physical Physical Physical Physical Verbal

12. Agitation in Dementia: Subtypes Cohen-Mansfield,J. 1996. 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. 2006. Biological Psychiatry. 59. 1029.

14. Treatment Algorithms: Evidence

15. Why do we need a pathway?

16. Pathway

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

25. Pathway

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

29. Multisensory Snoezelen System

30. Paro Therapeutic Robot

31. Pharmacological Interventions • For partial responders: • Extend the trial • Increase the dose • Augment with another • agent that showed also partial response • PRNs: • Trazodone • 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 1. Schneider L. Am J Geriatr Psych 2006:14(3) 191-212. 2. Ceitzet al. Cochrane Review, 2011. 3. Ballard & Corbett. 2013:25(3)252-259.

34. Antipsychotics • Mainstay of psychopharmacological treatment • Up to 40% of all dementia patients prescribed antipsychotics1 • Atypicals vs. typicals: perceived safety advantage • In patients with dementia, atypicals increase: • risk of death (OR=1.5 - 1.7) • cerebrovascular adverse events (OR=2.7) • rate of cognitive decline 1. Schneider L. Am J Geriatr Psych2006:14(3) 191-212. 2. Ballard & Corbet. Current OpinPysych. 2013:226(3)252-259. 3. Hermann & Lanctôt. Drug Safety. 2006:29(10) 833-843.

35. Atypical Antipsychotics Schneider L. Am J Geriatr Psych 2006:14(3) 191-212. Ballard et al. Cochrane Review. 2012.

36. Atypical Antipsychotics Schneider L. Am J Geriatr Psych 2006:14(3) 191-212. Ballard et al. Cochrane Review. 2012

37. Antidepressants • 1. Ballard & Corbegtt. Current Opin Psychiatry. 2013 26(3) 252-259. • 2. Pollock, BG, Mulsant, BH, Rosen J et al.Am J Pscychiatry 2002; 159:450-465. • 3. Pollock, Mulsant, Rosen et al. Am J Geriatr Psychiatry 2007;15:942-952

38. Antidepressants Martinonet al., Cochrane Review, 2008 Henry et al.Am J Alz Dis & Other Dementias 2011:26(3) 169-183.

39. Cognitive Enhancers Roddaet al. Int. Pyschoger 2009:21:5;813-24

40. Anticonvulsants & mood stabilizers • Yi-Chun & Ouyang. KaohJ of Med Sci (2012): 28, 185-193.

41. Yi-Chun & Ouyang. Kaoh J of Med Sci (2012): 28, 185-193.

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: 300-600 mg daily over 6-8 weeks

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

47. Dr.AmerBurhan • Dr. Simon Davies • Dr. Donna Kim • Dr. Benoit Mulsant • Dr. Bruce Pollock • Dr. Vincent Woo • Ms.RongTing • Dr.SawsanKalache • Ms. SaimaAiwan • Mr. Christopher Uranis