1. Behavioral and Psychological Symptoms of Dementia (BPSD)
Leon Kraybill MD CMD
Lancaster General Hospital Geriatric Fellowship
February 4, 2009

2. “Agitated” behavior What is the challenging behavior?
Whose problem is it?
Is it just not doing what “we” want “them” to do?

3. Behavioral and Psychological Symptoms of Dementia (BPSD)
A heterogeneous range of psychological reactions, psychiatric symptoms, and behaviors occurring in people with dementia of any etiology.
Any verbal, vocal, or motor activities not judged to be clearly related to the needs of the individual or the requirements of the situation
An observable phenomena (not just internal)

4. Objectives Identify the range of behaviors in dementia
Discuss possible causes of these behaviors
Review types of nonpharmacological responses
Review medications used for emotional relief

5. Prevalence of BPSD Present in all types of dementia
80-90% of patients develop at least 1 distressing symptom during the course of their dementia
60% of community dwelling patients with dementia
80% of dementia patients in nursing homes

6. BPSD – distressing for all
Individual – distress is key to tx decisions
Family - noncognitive symptoms are most distressing, could cope with a 'memory' disorder. Unpredictable violence or aggression = desperation
LTC staff need to understand and have tools for response

7. Consequences of BPSD Caregiver stress Increased ER visits
Prolonged hospital stays
Increased use of medications
Placement in LTC
Increased financial costs
**Decreased quality of life for patient and caregiver**

8. The “unmet needs” model (Cohen-Mansfield)
There is an underlying unmet need that is causing the inappropriate behavior.
This need is frequently not apparent to the observer or the caregiver,or else caregivers do not feel able to fulfill this need (example -sensory deprivation, boredom, and loneliness)
Ideally can identify and prevent the resident from reaching the point of unmet need
Possible responses:
Providing sensory stimulation, activities, and social contacts -The provision of hearing aids may decrease isolation due to sensory deprivation
Easily accessible outdoor area
Reduced levels of restraints
Sufficient levels of light
Good toileting procedures, better
Proper treatment of pain

9. Learning/behavioral models (Cohen-Mansfield)
Behavior is a learned connection between antecedents, behavior, reinforcement
Many problem behaviors are learned through reinforcement by staff members, who provide attention when problem behavior is displayed.
ABC approach
A = antecedent or triggering event that precedes the problem behavior
B= the behavior of concern
C= the consequence of that behavior
Changing either the antecedent or the consequence may change the behavior

10. Learning/behavioral models (Cohen-Mansfield)
Identify precisely the problem. The more clearly it is defined, the easier it is implement an effective response
Gather information about the circumstances surrounding the problem immediately before and after. There may be several triggers
Set realistic goals, and make plans to achieve them. Seek to be creative, realistic and tailored to the individual and caregivers. "Increasing pleasant activity" is more realistic than "be happy all the time.“
Encourage rewards (to all) for small successes. Changing behavior is hard work for everyone.
Continually evaluate and modify plans. Consistency but flexibility. Strategies may need to change.

11. Environmental vulnerability/reduced stress-threshold model (Cohen-Mansfield)
The dementia process results in greater vulnerability to surroundings and a greater chance that an event will affect behavior.
Persons with dementia progressively lose their coping abilities and therefore perceive their environment as more and more stressful.
Concurrently, their likelihood of being bothered by the environment increases, resulting in anxiety and inappropriate behavior when the environmental stimuli exceed the threshold for tolerating the stress
An environment of reduced stimulation is supposed to limit the stress experienced and thereby reduce the level of inappropriate behavior
Relaxation will reduce the stress and thereby decrease the undesirable behavior.

12. Terminology
Agitation – abnormal behavior (ie aggression, restlessness, etc.)
Psychosis – abnormal perceptions/beliefs that may lead to agitated behavior (ie paranoid delusions)
Dementia treatment principle: agitation generally responds better than psychosis

13. Range of behavior Psychosis (delusions or hallucinations)
Agitation/aggression
Apathy/indifference
Depression/dysphoria
Anxiety
Elation/euphoria
Disinhibition
Irritability/lability
Aberrant motor behavior
Insomnia
Appetite disruption
From Neuropsychiatric Inventory (NPI) rating scale (Cummings et al. 1994)

14. Subtypes of BPSD (Cohen-Mansfield) see handout
Physically aggressive behaviors (hitting, kicking, biting)
Physically nonaggressive behavior (pacing, inappropriate touching)
Verbally nonaggressive agitation (repetitive phrases or requests, calling out)
Verbally aggressive behaviors (cursing, screaming)

15. BPSD vs other causes
Acute/evolving/sudden is often med related or other medical disease
Progression of underlying dementia – generally more insidious and persistant

16. Evaluation
Obtain a clear description of problem behavior, temporal onset, course, circumstances
Assess ability to express basic needs (hunger, thirst, fatigue)
Look for delirium – acute/rapid change (dehydration, UTI, pneumonia, angina, constipation, pain, uncontrolled DM)
Look for mood disturbance (sadness, irritability, withdraw)
Check med changes – always suspect the meds
Ask about environmental precipitants: change in routine, roommate, caregiver, overstimulation/understimulation, other disruptive patients, family illness

17. Framework for treating agitation:
Important to adopt a pragmatic approach to treatment
Most situations allow for an initial non-pharmacological approach to management
“Four D” Method
Define and Describe
Decode
Design and Implement
Determine

18. Principles of restorative care
Focus on bigger picture of health and emotional wellbeing, rather than just “problem behavior”
Capitalize on the individual’s remaining abilities and strengths
Create an enabling and motivating environment
Provide appropriate tasks and assistance (ie activities that will be successful)
Practice and repetition are needed (repetition is the mother of learning)

19. Staff Techniques Communicate face to face, speak slowly & clearly
Use verbal clues
Approach slowly and deliberately (don’t surprise)
Serve as a “calming force”
Humor and laughter
Know what makes the resident tick
Act as if they function at a higher level of cognition
Sensory experience: music, dance, visual contrast, fragrances, foods, tactile stimulation
Distraction, redirection
Flexibility, “go with the resident’s pace”
Anticipate challenges and difficulties – they are the norm

20. Behavioral interventions
Tx underlying medical illness
Correct sensory deficits
Remove offending medications
Keep environment comfortable, calm, homelike
Regular daily activities and structure
Assess sleep and eating patterns
Educate and support caregiver

21. Nonpharmacologic interventions
See handout - Specific situations of agitation

22. Medication for BPSD
Currently there are no FDA approved treatments for agitation and psychosis in dementia

23. FDA Blackbox on antipsychotics
WARNING: INCREASED MORTALITY FOR ELDERLY PATIENTS WITH DEMENTIA RELATED PSYCHOSES. Elderly patients with dementia related psychoses are at increased risk for death compared to placebo. This drug is not approved for the treatment of dementia related psychoses.

24. FDA Blackbox warning
Meta-analysis of 17 double blind RCT’s in elderly dementia patients, April Atypicals associated with a times greater risk of mortality compared to placebo. Most deaths from cardiac or infectious etiology, in some studies – strokes.
Extended to all antipsychotics in June 2008

25. Common side-effects of antipsychotics
Extrapyramidal symptoms (akathisia, dystonia, psuedoparkinsonism, and dyskinesia)
Sedation
Tardive dyskinesia – should screen regularly
Dyskinesia Identification System: Condensed User Scale (DISCUS)
Abnormal Involuntary Movement Scale (AIMS)
Gait disturbances
Falls
Meta-analysis shows a significant increase in respiratory tract and urinary tract infections and peripheral edema in patients treated with risperidone versus placebo (Ballard et al. 2006)

26. Study
Older adults with dementia: 20,682 in community, 20,559 in LTC
Control: No antipsychotics
Outcomes: serious events in first 30 days
Community dwellers:
Atypicals: 13.9% had a serious event (3.2 times higher than control)
Typicals: 3.8 times higher serious event
LTC
Atypicals: 1.9 times higher serious events than control
Typicals: 2.4 times higher serious event
Rochon PA. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168:

27. CATIE-AD Trial
First cost-benefit analysis of second generation antipsychotics in treating non-cognitive symptoms in AD patients
421 AD patients with psychosis and aggression where randomly assigned to olanzapine, quetiapine, risperidone, or placebo of “watchful waiting” over 9 months
No statistical differences between groups, although placebo most often superior in net health benefit analysis
Olanzapine group – more impaired on ADL testing- ???sedation, gait disturbance
Placebo group – best ADL score, lower dependence score, lower total health care costs - $50-100
Several methodological drawbacks:
Subjects were outpatients, less impaired then some BPSD trials
High dropout rate compared to other RCTs (likely a design feature)
No washout period
Dosage likely too low for quetiapine (mean 56.5mg/day)
Authors concluded adverse events offset advantages in efficacy
Clinical Antipsychotic Trial of Intervention Effectiveness – Alzheimer’s Disease. Rosenheck, Cost-benefit analysis…., Arch Gen. Psychiatry 2007; 64(11):

28. Antipsychotics in LTC
Only 2 RCTs have examined antipsychotics in AD over 6 months
Ballard et al (2005) found no difference between quetiapine, rivastigmine, or placebo in agitation over 6 months

29. Atypicals vs typicals
Atypicals block excessive dopamine transmission, which is beneficial in schizophrenics.
Elderly patients (especially dementia) have accelerated dopamine loss and tend to experience more severe motor side effects than younger patients.
Less likely to trigger extrapyramidal symptoms/tardive dyskinesia
No difference in safety, efficacy

30. Atypical doses
Olanzapine 5-10 mg/day and Risperidone 1mg/day appear to have low incidence of EPS, but somnolence remains a concern
See handout

31. Recommendations Look for etiology of symptoms
Use caution in these fragile and vulnerable patients
Need shared decision making – staff, families, patients
Identify target signs and symptoms, and set a limited time frame (many patients improve without treatment over 2-4 weeks)
Treat only severe symptoms, emotional distress, physical safety
Use the lowest dosages for shortest time
Possible doses used:
Risperidone (Risperdal) mg/day
Olanzapine (Zyprexa) 5-10 mg/day
Quetiapine (Seroquel) mg/day
Aripiprazole (Abilify) 7-12 mg/day
Monitor, assess regularly
Taper and trial discontinuation regularly
White paper of American College of Neuropsychopharmacology – reviewed July 18, 2007 in Neuropsychopharmacology

32. Documentation Target behavior, duration and circumstances
Emotional and physical consequences of the behavior
Nonpharmacological interventions
Team discussions and interventions
Discussions with resident/POA/family regarding the circumstances, the risk of medication (death), and consent for treatment
Can someone else read your documentation and be able to explain what happened and why the treatments were chosen?

33. Serotonergic agents (2005)
Well tolerated
Beneficial for depression
Not clearly effective in tx of other sx
Pharmacological treatment of Neuropsychiatric symptoms of dementia: A review of the evidence. JAMA 2005;293(5);

34. Citalopram vs risperidone study (2007)
To alleviate severe agitation and psychotic symptoms associated with dementia in nondepressed elderly (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions)
Efficacy:
Citalopram overall 32% reduction of symptoms
Risperidone - 35% reduction
Total adverse-event scores
Increased 19% with risperidone
Decreased by 4% with citalopram
Citalopram worked on psychotic symptoms like hallucinations and delusions!
Suggests agitation and psychosis in younger and older populations have different neurochemistry.
A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry Nov;15(11): Epub 2007 Sep 10. (53 patients were randomized to citalopram and 50 to risperidone)

35. Haldol for agitation in dementia (2005 Cochrane review)
No significant improvement in agitation, compared with controls
Aggression decreased (not other aspects of agitation)
Dosages mg/day
Recommendations
Haloperidol was useful in reducing aggression, but was associated with adverse effects
No evidence to support the routine use of this drug for other manifestations of agitation in dementia
Haloperidol should not be used routinely to treat patients with agitated dementia

36. Trazodone for agitation in dementia (2004 Cochrane review)
Rationale: BPSD may be due to serotonergic dysfunction
A sedating atypical serotonergic antidepressant with a lower rate of adverse effects may help
Limited data from two small studies
Conclusions: Insufficient evidence to recommend the use of trazodone

37. Valproate preparations for BPSD (2004 Cochrane review)
No evidence of efficacy of valproate preparations for treatment of BPSD
Adverse reactions
Sedation occurred more frequently than in controls
Urinary tract infection was more than in controls
Low dose with valproate preparations is ineffective in treating BPSD
High dose therapy is associated with an unacceptable rate of adverse effects

38. Cholinesterase inhibitors
Initial studies focused on cognition, yet there is increasing evidence of a possible behavioral benefit as well
Meta-analysis of ChEI studies - Modest but significant behavioral benefit compared with placebo Trinh et al. (2005)
Several post-hoc analyses of studies with galantamine and donepezil suggest beneficial effects on psychosis, agitation, mood, apathy, and aberrant motor behaviors
(Mega et al. 1999; Herrmann et al. 2005; Cummings et al. 2006)

39. Cholinesterase inhibitors
Data review suggest a statistically significant difference
But magnitude of effect is small, and of questionable clinical significance

40. Memantine
3 studies have examined the effect of memantine on BPSD in moderate-severe AD
Post-hoc analysis suggests benefits, particularly for aggressive, agitated behaviors (Gauthier S et al 2005; Cummings et al. 2006)
Memantine also appears to delay emergence of agitation and reduce caregiver distress (Cummings et al 2006)
Other reviewers question the clinical significance of the benefit

41. Carbamazepine The Good News:
4 RCTs demonstrate benefit for aggression and agitation (Tariot el al. 1994; Cooney et al. 1996; Tariot et al. 1998; Olin et al. 2001)
Tariot et al. (1998) completed a nursing home study where 72% of patients improved versus only 21% placebo
One of the largest effect sizes of all BPSD trials
The Bad News: Concerns about tolerability in elderly, drug-drug interactions, and adverse events unfortunately limit its use

42. Benzodiazepines Several studies support efficacy
Main concern is high rate of adverse events in the elderly
Excessive sedation, falls, cognitive impairment, paradoxical agitation
Guidelines support only short-term as-needed use

43. What if we stop meds?
3 placebo controlled withdrawal studies indicated no worsening of behavior when long-term administration of neuroleptics were stopped
(Cohen-Mansfield et al. 1999; Bridge-Parlet. 1997; Ballard et al. 2004)

44. Sexually inappropriate behaviors
Likely more due to disinhibition, than hypersexuality
Occurs in 7-25% of significantly impaired older
SSRI
Antiandrogen
Progesterone 5 mg po daily (10 mg IM weekly)
Leuprolide 5-10 mg IM monthly

45. Parkinsonian motor disturbances & meds
Dementia with Lewy bodies (DLB), Parkinson disease (PD) and up to 50% of Alzheimer disease (AD)
Neuroleptic antipsychotics are dopamine receptor antagonist
Severe motor deterioration (neuroleptic sensitivity)
Small trial (9 subjects) Quetiapine ( daily, mean 120) vs placebo
No difference in cognitive or behavioral scores
Adverse reactions – similar, except ↑ dizziness in quetiapine
Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology - Volume 68, Issue 17 (April 2007)
Quetiapine - dosages of 200 mg/day or higher may be needed to control agitation in demented patients
Zhong K, Tariot PN, Mintzer J, et al. Quetiapine for the treatment of agitation in elderly institutionalized patients with dementia: a randomized, double-blind trial. Presented at the American College of Neuropsychopharmacology Annual Meeting; December 12–16, 2004; San Juan, Puerto Rico.

46. Manic-like syndromes
Sx: pressured speech, disinhibition, elevated mood, intrusiveness, hyperactivity, reduced sleep
Likely secondary to the dementia
Coexist with confusional state
Irritable/hostile > euphoria
Consider divalproex 125 BID

47. Apathy or depression?
Often confused with depression, since symptoms overlap (diminished interest, hypersomnia, fatigue, lack of insight, psychomotor retardation)
Apathy traits: emotional indifference, denying feelings of depression, reduced ability to initiate in multiple domains (cognitive, motor, gait)
Meds to increase dopaminergic transmission: Bupriopion, amantadine, psychostimulants (Ritalin,etc), rivastigmine (Exelon), donepezil (Aricept). SSRIs may help but produce agitation.

48. What don’t meds help?
Meds don’t help general agitation – especially wandering

49. F-tag 329 Doses above these milligrams trigger scrutiny:
Haloperidol (Haldol) 4 mg
Risperidone (Risperdal) 2 mg
Olanzapine (Zyprexa) 10 mg
Quetiapine (Seroquel) 200 mg

50. F-tag 329
The facility must assure that residents who are undergoing antipsychotic drug therapy receive adequate monitoring for significant side effects of such therapy with emphasis on the following:
Tardive dyskinesia;
Postural (orthostatic) hypotension;
Cognitive/behavior impairment;
Akathisia
Parkinsonism.

51. F-tag 329 (12/06 update)
During the first year in which a resident is admitted on a psychopharmacological medication (other than an antipsychotic or a sedative/hypnotic), or after the facility has initiated such medication, the facility should attempt to taper the medication during at least two separate quarters (with at least one month between the attempts), unless clinically contraindicated. After the first year, a tapering should be attempted annually, unless clinically contraindicated. The tapering may be considered clinically contraindicated, if:
The continued use is in accordance with relevant current standards of practice and the physician has documented the clinical rationale for why any attempted dose reduction would be likely to impair the resident’s function or cause psychiatric instability by exacerbating an underlying medical or psychiatric disorder; or
The resident’s target symptoms returned or worsened after the most recent attempt at tapering the dose within the facility and the physician has documented the clinical rationale for why any additional attempted dose reduction at that time would be likely to impair the resident’s function or cause psychiatric instability by exacerbating an underlying medical or psychiatric disorder.

52. Summary for gradual dose reduction (GDR) – F-tag 329
Within 1st year after admission on antipsychotic or after initiation: GDR in 2 separate quarters, with at least one month between attempts
After 1st year - GDR annually