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

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

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)

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

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

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

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**

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

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

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.

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.

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

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)

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)

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

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

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

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)

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

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

Nonpharmacologic interventions See handout - Specific situations of agitation

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

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.

FDA Blackbox warning Meta-analysis of 17 double blind RCT’s in elderly dementia patients, April 2005. Atypicals associated with a 1.6-1.7 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

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) http://www.dhs.state.mn.us/main/groups/licensing/documents/pub/dhs_id_057837.pdf Abnormal Involuntary Movement Scale (AIMS) www.cqaimh.org/pdf/tool_aims.pdf 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)

Study - 2008 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;168:1090-1096.

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):1259-1268.

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

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

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

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) 0.5-1.5 mg/day Olanzapine (Zyprexa) 5-10 mg/day Quetiapine (Seroquel) 50-200 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

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?

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); 596-608

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. 2007 Nov;15(11):942-52. Epub 2007 Sep 10. (53 patients were randomized to citalopram and 50 to risperidone)

Haldol for agitation in dementia (2005 Cochrane review) No significant improvement in agitation, compared with controls Aggression decreased (not other aspects of agitation) Dosages 1.2-3.5 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 www.cochrane.org/reviews/en/ab002852.html

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 www.cochrane.org/reviews/en/ab004990.html

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

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)

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

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

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

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

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)

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

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 (25-300 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.

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

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.

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

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

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.

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. www.cms.hhs.gov/transmittals/downloads/R22SOMA.pdf

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