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Larry W Lawhorne, MD Professor and Chair, Dept of Geriatrics Boonshoft School of Medicine Wright State University Dayton OH. Everything is complicated. If that were not so, life and poetry and everything else would be a bore. Poet Wallace Stevens. Dementia-Associated

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Larry W Lawhorne, MD

Professor and Chair, Dept of Geriatrics

Boonshoft School of Medicine

Wright State University

Dayton OH


Everything is complicated.

If that were not so, life and

poetry and everything else

would be a bore.

Poet Wallace Stevens


Dementia-Associated

Behavioral Symptoms:

Why are recognition, assessment,

treatment, and monitoring so

complicated?




  • Prevalence of dementia: 52.58% sample surveys of U.S. nursing homes.

    > 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


  • 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.


  • The odds of receiving atypical antipsychotic treatment typical agents (1.75%).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.


  • I am not a geriatric psychiatrist but know when to call one typical agents (1.75%).

  • 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


  • 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.


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


  • Surveyor view… distressing, disturbing or disruptive.

  • Provider view…

  • Different versions of the truth?


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?


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?


  • Dementing illnesses with associated behavioral symptoms 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?

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


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.


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 experiencinginconsolable or persistent distress, significant decline in function, and/or substantial difficulty receiving necessary care.


  • 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.


Show of hands. distressing symptoms at the end of life.


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

  • Agree

  • Disagree

  • Neither agree nor disagree


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

  • Agree

  • Disagree

  • Neither agree nor disagree


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


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

  • Agree

  • Disagree

  • Neither agree nor disagree


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

  • Agree

  • Disagree

  • Neither agree nor disagree



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 .


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 .


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.


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.


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


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.


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.


  • 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.


CATIE-AD Trial such as quetiapine (Seroquel) may result in QoL improvements.

(Schneider et al. NEJM 2006)


No differences in efficacy between such as quetiapine (Seroquel) may result in QoL improvements.

placebo and the atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) in treating psychosis, aggression, and agitation in dementia.



  • 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.


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.”


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.


  • Total of 5106 patients. 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.

  • 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).


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.


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.


  • 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.


… requires ongoing respectful dialogue! dementia-associated behavioral symptoms is the lack of a “coherent language” to represent the benefits and risks of the drugs.


The Michigan Department of Community Health dementia-associated behavioral symptoms is the lack of a “coherent language” to represent the benefits and risks of the drugs.



Were behaviors characterized in agreement or consensus.

enough detail (onset, trigger, nature,

intensity, duration, frequency,

consequences, and other relevant

information)?


Was there documentation that agreement or consensus.

justified why the behavior was

considered problematic?


Was there timely recognition of agreement or consensus.

problematic behavior?


Were specific behaviors identified agreement or consensus.

for which a medication or other intervention was provided?


Was the current medication regimen agreement or consensus.

reviewed as a potential source of

problematic behavior?


If a plausible cause was not found agreement or consensus.

readily in someone with an acute

behavior change, were fluid and

electrolyte imbalance, acute infection,

pain, or other potential causes

considered?



K the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.” nown medical and neuropsychiatric conditions

Infection or new medical or neuropsychiatric condition

Side effect of medication

Something suggesting pain

Environmental factors

Social or spiritual issues


  • Adverse effect of a drug, especially an the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

    antimuscarinic or anticholinergic

  • Delirium associated with an acute medical

    condition, such as UTI, dehydration, or upper respiratory infection

  • Chronic medical condition, osteoarthritic

    or ischemic pain

  • Cognitive symptoms, such as frustration

    from memory problems


  • Unmet physical needs (hunger, toileting) the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

  • 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-giving


Everything is complicated. the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

If that were not so, life and

poetry and everything else

would be a bore.

Poet Wallace Stevens


Was there an attempt to identify the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

categories of cause(s) of any

problematic behavior, OR explain why

causes could or should not be sought?


Was a plausible explanation offered the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

as to how it was determined that

certain causes were the most likely

reason for the behavior?


Were specific goals and objectives the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

identified for managing behaviors?


Were appropriate individuals the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

consulted in planning the management

of problematic behavior?


Was cause-specific management the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

used OR an explanation why it was

not feasible or not provided?


Was a rationale documented for the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”

the specific choice of interventions?


Everybody advocates non-drug but difficult… the window, mutters something about her son coming home from work, wringing her hands, and asking for someone to help her.”


  • 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



Was there some documented because…”

explanation, in conjunction with a

physician, for the dose, frequency, and

duration of medication treatments?


Because of their risk of causing side effects, medications prescribed for problematic behaviors should be used

for specific indications, at the lowest effective dose, and for the shortest possible period of time.


Were the individual’s behavior and prescribed for problematic behaviors should be used

related causes monitored and

treatment adjusted accordingly?




Were the risks for significant the resident’s condition may change over time. Periodic monitoring is part of a systematic approach to care.

complications and problems related to

interventions identified and

addressed?


Were possible significant adverse the resident’s condition may change over time. Periodic monitoring is part of a systematic approach to care.

drug reactions (ADRs) or other

complications of psychoactive

medications considered?


Is there a difference? the resident’s condition may change over time. Periodic monitoring is part of a systematic approach to care.





Effectiveness “efficacious” prominently and the word “benefit” never appeared. 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.


Benefit “efficacious” prominently and the word “benefit” never appeared. 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.


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


  • 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.


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.


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.


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.


For an electronic version of the updated PowerPoint presentation, email me at

[email protected]


  • Available since the mid-1950's. presentation, email me at

  • Some of the more commonly used medications include:

    > Chlorpromazine (Thorazine)

    > Haloperidol (Haldol)

    > Perphenazine (generic only)

    > Fluphenazine (generic only).


  • Aripiprazole presentation, email me at (Abilify)

  • Clozapine (Clozaril)

  • Olanzapine (Zyprexa)

  • Quetiapine (Seroquel)

  • Risperidone (Risperdal)

  • Ziprasidone (Geodon, Zeldox)


  • A benzodiazepine,

    e.g., oxazepam (Serax)

  • Antipsychotics


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

  • Memantine (Namenda) and a cholinesterase inhibitor


  • Begin or raise dose of antipsychotic

  • An anticonvulsant

  • An SSRI

  • Low-dose trazodone (Desyrel)


No drug specifically addresses wandering, hoarding, or presentation, email me at

resistance to care, behaviors that are particularly frustrating

to caregivers.


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.


Managing the behavioral symptoms of dementia requires attention to the environmental and psychosocial

context in which they occur, as well as to comorbidities and potential adverse drug effects.


Evidence for the efficacy of antidepressants for depression attention to the environmental and psychosocial

in dementia is limited.


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