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Larry W Lawhorne, MDProfessor and Chair, Dept of GeriatricsBoonshoft School of MedicineWright State UniversityDayton OH

Everything is complicated. If that were not so, life and poetry and everything else would be a bore.

Poet Wallace Stevens

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Dementia-AssociatedBehavioral Symptoms: Why are recognition, assessment,treatment, and monitoring socomplicated?

New slides from the National Nursing Home Survey

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One in a continuing series of nationally representative sample surveys of U.S. nursing homes.

Conducted1973-1974 and repeated in 1977, 1985, 1995, 1997, 1999, and 2004.

Provides basic information about nursing homes, the services provided, their staff, and their residents.

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Prevalence of dementia: 52.58%> 77% Female> 56% ≥85 years of age > 97% non-Hispanic; 88% White

Antipsychotic medications were taken by 32.88% of residents with dementia

http://www.cdc.gov/nchs/nnhs.htm

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More residents received atypical agents (31.63%) than typical agents (1.75%).

Males with dementia more likely than females with dementia to receive antipsychotic agents .

Atypical antipsychotic use increased with dependence in decision-making ability, indicators of depressed mood and behavioral symptoms.

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The odds of receiving atypical antipsychotic treatment increased with the diagnosis of schizophrenia, bipolar mania and anxiety among dementia patients.

The likelihood of receiving atypical antipsychotic agents decreased with increasing dependence for out-of-bed mobility.

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I am not a geriatric psychiatrist but know when to call one

I believe in the value of the IDT I believe in the importance of

observations by and suggestions from direct care staff and families

I believe in the utility of Clinical Process Guidelines

I receive no pharmaceutical support

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Evaluating dementia-associated behaviors that are distressing, disturbing or disruptive.

Considering the role of antipsychotic drugs for these behavioral symptoms.

Comparing care for chronic medical conditions with care for degenerative neuropsychiatric disorders.

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Evaluating dementia-associated behaviors that are distressing, disturbing or disruptive.

Considering the role of antipsychotic drugs for these behavioral symptoms.

Comparing care for chronic medical conditions with care for degenerative neuropsychiatric disorders.

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Surveyor view… Provider view… Different versions of the truth?

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Are these different versions of the truth or do they reflect a lack of a “coherent language” to represent the benefits and risks of atypical antipsychotics (AAPs) for residents with dementia-associated behavioral symptoms?

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How valid and valuable is the existing “evidence” as presented in articles in peer-reviewed journals on efficacy and safety of AAPs for the indications listed in Appendix PP of the CMS State Operations Manual?

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› Dementing illnesses with associated behavioral symptoms

› Medical illnesses or delirium with manic or psychotic symptoms and/or treatment-related psychosis or mania (e.g., thyrotoxicosis, neoplasms, high-dose steroids)

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Diagnosis alone is not sufficient to begin a drug; at least one of the additional criteria must also be met: › Symptoms are caused by mania or

psychosis.› Behavioral symptoms present a

danger to resident or others.› Symptoms are severe enough that

resident is experiencing inconsolable or persistent distress, significant decline in function, and/or substantial difficulty receiving necessary care.

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Diagnosis alone is not sufficient to begin a drug; at least one of the additional criteria must also be met: › Symptoms are caused by mania or

psychosis.› Behavioral symptoms present a

danger to resident or others.› Symptoms are severe enough that

resident is experiencing inconsolable or persistent distress, significant decline in function, and/or substantial difficulty receiving necessary care.

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Antipsychotics may be helpful in the treatment of distressing symptoms at the end of life.

A drug such as haloperidol may be used for hiccups, nausea and vomiting associated with cancer or cancer chemotherapy, or adjunctive therapy at end of life as long as rationale is well documented.

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Show of hands.

AAPs are used to treat dementia-associated behavioral symptoms in nursing facility residents.

Agree Disagree Neither agree nor disagree

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AAPs are over-used in the treatment of dementia- associated behavioral symptoms in nursing facility residents.

Agree Disagree Neither agree nor disagree

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AAPs are used more in the U.S. than in Canada, UK or France to treat dementia- associated behavioral symptoms in nursing facility residents.

Agree Disagree Neither agree nor disagree

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The effectiveness of AAPs in treating dementia-associated behavioral symptoms in nursing facility residents is over-rated.

Agree Disagree Neither agree nor disagree

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The danger of AAPs in treating dementia- associated behavioral symptoms in nursing facility residents is over-stated.

Agree Disagree Neither agree nor disagree

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…need better research untainted by a sponsor’s funding or a researcher’s biases!

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By looking at the list of authors on a paper and glancing at the title, one can often predict the conclusion:

If authors A,B, and C are listed, then AAPs are safe and effective…if not effective, then certainly beneficial.

If authors D,E, and F, then AAPs are ineffective, dangerous, and not at all beneficial .

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By looking at the list of authors on a paper and glancing at the title, one can often predict the conclusion:

If authors A,B, and C are listed, then AAPs are safe and effective…if not effective, then certainly beneficial.

If authors D,E, and F, then AAPs are ineffective, dangerous, and not at all beneficial .

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Authors D, E, and F accuse authors A,B, and C of being pawns of the drug industry and marketing dangerous drugs to vulnerable older adults on the basis of corrupt research.

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Authors A, B, and C say that authors D, E, and F are not clinician scientists who gather and analyze hard data but rather nihilistic academics who respond to sentinel events and sentimentality while riding a wave of public opinion opposed to nursing facilities and the medicalization of aging.

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The following slides are not in your handout but can be obtained by email as described at the end of the presentation.

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Low-dose, once-a-day olanzapine and risperidone appear to be equally safe and equally effective in the treatment of dementia-related behavioral disturbances in residents of extended care facilities.

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In an elderly NH population, there was no evidence that short-term use (median 13.1 weeks) of atypical antipsychotic agents was associated with the onset or worsening of diabetes.

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Preliminary evidence indicates that atypical antipsychotics such as quetiapine (Seroquel) may result in QoL improvements.

The inclusion of systematic QoL measures in future clinical trials is imperative in order to provide evidence to enable the clinician to make informed judgments regarding the potential benefits or risks of pharmacologic treatment for individual patients.

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CATIE-AD Trial(Schneider et al. NEJM 2006)

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No differences in efficacy betweenplacebo and the atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) in treating psychosis, aggression, and agitation in dementia.

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Rates of drug discontinuation due to adverse effects ranged from 5% for placebo to 24% for olanzapine.

Overall, 82% of the patients stopped taking their initially assigned medications during the 36-week period of the trial.

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During treatment of nursing home residents with dementia with antipsychotics, the severity of most behavioral problems continues to increase in most patients, with only one out of six patients showing improvement.

After withdrawal of antipsychotics, behavioral problems remained stable or improved in 58% of patients.

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A Public Health Advisory released on 4/11/2005 states that the FDA has “determined that the treatment of behavioral disorders in elderly patients with dementia with atypical (second generation) antipsychotic medications is associated with increased mortality.”

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15 of 17 placebo controlled trials performed with olanzapine (Zyprexa), aripiprazole (Abilify), risperidone (Risperdal), or quetiapine (Seroquel) in elderly demented patients with behavioral disorders showed numerical increases in mortality in the drug-treated group compared to the placebo-treated patients.

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Total of 5106 patients. 1.6-1.7 x increase in mortality. Specific causes of deaths due to

heart related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

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Conventional antipsychotics are associated with a higher risk of all-cause mortality than atypical agents. It seems advisable that they are not used in substitution for atypical antipsychotics among nursing home residents with dementia even when short-term therapy is being prescribed.

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Residents were at increased risk of death simply by being admitted to a facility with a higher intensity of antipsychotic drug use, despite similar clinical characteristics at admission.

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The fundamental problem in the testing and use of AAPs for dementia-associated behavioral symptoms is the lack of a “coherent language” to represent the benefits and risks of the drugs.

“Coherent language” means a set of words, phrases, and descriptors that makes sense for all stakeholders…researchers, clinicians, residents, families, caregivers, policy makers, and even providers and surveyors.

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… requires ongoing respectful dialogue!

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The Michigan Department of Community Health

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…create a situation where there is always complete agreement or consensus.

Were behaviors characterized inenough detail (onset, trigger,

nature,intensity, duration, frequency,consequences, and other relevantinformation)?

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Was there documentation thatjustified why the behavior wasconsidered problematic?

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Was there timely recognition ofproblematic behavior?

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Were specific behaviors identifiedfor which a medication or other intervention was provided?

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Was the current medication regimenreviewed as a potential source ofproblematic behavior?

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If a plausible cause was not foundreadily in someone with an acutebehavior change, were fluid andelectrolyte imbalance, acute

infection,pain, or other potential causesconsidered?

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“The resident is restless and repeatedly gets up, walks to the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

She is not eating and drinking because of the behavioral symptoms and is at risk for dehydration.

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Known medical and neuropsychiatric conditions

Infection or new medical or neuropsychiatric condition

Side effect of medicationSomething suggesting painEnvironmental factorsSocial or spiritual issues

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Adverse effect of a drug, especially anantimuscarinic or anticholinergic

Delirium associated with an acute medicalcondition, such as UTI, dehydration, or upper respiratory infection

Chronic medical condition, osteoarthriticor ischemic pain

Cognitive symptoms, such as frustrationfrom memory problems

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Unmet physical needs (hunger, toileting)

Unmet psychological needs caused by separation from spouse or family (such as when a spouse is hospitalized or placed in a nursing home)

Environmental precipitants (noise, crowded conditions, strangers in the home)

Unsophisticated care-giving57

Everything is complicated. If that were not so, life and poetry and everything else would be a bore.

Poet Wallace Stevens

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Was there an attempt to identifycategories of cause(s) of anyproblematic behavior, OR explain

whycauses could or should not be

sought?

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Was a plausible explanation offeredas to how it was determined thatcertain causes were the most likelyreason for the behavior?

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Were specific goals and objectivesidentified for managing behaviors?

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Were appropriate individualsconsulted in planning the

managementof problematic behavior?

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Was cause-specific managementused OR an explanation why it wasnot feasible or not provided?

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Was a rationale documented forthe specific choice of interventions?

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Everybody advocates non-drug but difficult…

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N = 81 residents; Intervention: consciousness-raising, educational sessions, and clinical follow-up; 6-month study

Measures: discontinuations and dose reductions of antipsychotics, use of other psychotropics and restraints, frequency of disruptive behaviors, and stressful events experienced by nursing staff and personal care attendants.

Results: Substantial reduction in the number of residents receiving antipsychotics and decrease in the frequency of disruptive behaviors.

Int J Geriatr Psychiatry. 2008 Jun;23(6):574-9

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“We are initiating the following interventions because…”

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Was there some documentedexplanation, in conjunction with aphysician, for the dose, frequency,

andduration of medication treatments?

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Because of their risk of causing side effects, medications prescribed for problematic behaviors should be usedfor specific indications, at the lowest effective dose, and for the shortest possible period of time.

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Were the individual’s behavior andrelated causes monitored andtreatment adjusted accordingly?

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A systematic approach and descriptive documentation help the staff to see more clearly the outcomes of treatment, to measure the results more objectively, and to determine if modifications are necessary or appropriate.

Continued on next slide

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Underlying causes of problematic behavior may resolve, or the resident’s condition may change over time. Periodic monitoring is part of a systematic approach to care.

Lack of anticipated response to treatment requires reevaluation of approaches.

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Were the risks for significantcomplications and problems related

tointerventions identified andaddressed?

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Were possible significant adversedrug reactions (ADRs) or othercomplications of psychoactivemedications considered?

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Is there a difference?

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Producing result: causing a result, especially the desired or intended result

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Promoting or enhancing well-being

Advantageous

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Early trials used the words “effective” and “efficacious” prominently and the word “benefit” never appeared.

Later studies almost all spoke to “benefits” or to the “beneficial” impact of treatment with Aricept.

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Effectiveness is determined by short-term, observable measurements, e.g., blood pressure readings in hypertension studies, scores on tests of cognition in dementia studies, or the NPI (Neuropsychiatric Inventory) in studies on Atypical Antipsychotics.

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Benefit is much more difficult to measure and can be influenced by marketing, spin, advertising, repeating the same things over and over even if they may not be true…and hope.

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Doctors, families, and others need to realize that effective drug treatment may require years to show benefit

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An Intervention can be

Beneficial Not Beneficial

Effective X

Not Effective

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An Intervention can be

Beneficial Not Beneficial

Effective X

Not Effective

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An Intervention can be

Beneficial Not Beneficial

Effective

Not Effective X

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An Intervention can be

Beneficial Not Beneficial

Effective

Not Effective X

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Blood Pressure Treatment

Beneficial Not Beneficial

Effective Clinical trial evidence to support.

Not Effective

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Cholesterol-lowering drugs for residents with terminal condition on Hospice

Beneficial Not Beneficial

Effective Expert opinion and consensus support.

Not Effective

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Music therapy for residents with dementia

Beneficial Not Beneficial

Effective

Not Effective Expert opinion and consensus

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Antipsychotics for dementia associated behavioral symptoms

Beneficial Not Beneficial

Effective Authors A,B, and C

Not Effective Authors D, E and F

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Antipsychotics for dementia associated behavioral symptoms

Beneficial Not Beneficial

Effective It depends

Not Effective on the resident!

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For medical conditions such as hypertension, diabetes or cancer, the health sciences developed reasonable expertise in diagnosis and staging before developing expertise in treatment.

For dementia-associated behavioral symptoms, we are trying to develop diagnostics, staging, and interventions all at the same time.

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1. Dementia-associated behavioral symptoms occur across all settings of care, and we do not manage them well.

2. Non-drug approaches are under-utilized but translating these approaches from studies conducted by researchers invested in them into our every day work is hard.

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3. AAPs are probably over-utilized or at least not always prescribed for the right resident, at the right time, at the right dose, for the right reason, and for the right length of time.

4. On the other hand, AAPs probably are both effective and beneficial for some residents with dementia-associated behavioral symptoms.

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5. One way to identify residents with dementia-associated behavioral symptoms who are most likely to benefit from AAPs and to administer them as safely as possible is to follow a systematic approach such as the one outlined in the Michigan Department of Community Health Clinical Process Guideline on Behavior Management and Antipsychotic Medication Prescribing.

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For an electronic version of the updated PowerPoint presentation, email me atlarry.lawhorne@wright.edu

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Available since the mid-1950's. Some of the more commonly used

medications include:> Chlorpromazine (Thorazine)> Haloperidol (Haldol)> Perphenazine (generic only)> Fluphenazine (generic only).

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Aripiprazole (Abilify) Clozapine (Clozaril) Olanzapine (Zyprexa) Quetiapine (Seroquel) Risperidone (Risperdal) Ziprasidone (Geodon, Zeldox)

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Alcohol or benzodiazepinewithdrawal

No alcohol or benzodiazepinewithdrawal

A benzodiazepine,e.g., oxazepam (Serax)

Antipsychotics

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Mild to moderate dementia

Moderate to severe dementia

Cholinesterase inhibitors, e.g., donepezil (Aricept)

Memantine (Namenda) and a cholinesterase inhibitor

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Delusions, hallucinations, orphysical aggression

Impulsivity Two or more

symptoms of lowmood

Difficulty sleeping

Begin or raise dose of antipsychotic

An anticonvulsant An SSRI

Low-dose trazodone (Desyrel)

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No drug specifically addresses wandering, hoarding, orresistance to care, behaviors that are particularly frustratingto caregivers.

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Many drugs are sedating and increase the risk of falling and injury; antipsychotic use is off-label for dementia and carries significant and possibly lethal adverse effects.

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Managing the behavioral symptoms of dementia requires attention to the environmental and psychosocialcontext in which they occur, as well as to comorbidities and potential adverse drug effects.

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Evidence for the efficacy of antidepressants for depressionin dementia is limited.

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