Larry W Lawhorne, MD Professor and Chair, Dept of Geriatrics Boonshoft School of Medicine Wright State University Dayton

1. Larry W Lawhorne, MD Professor and Chair, Dept of Geriatrics Boonshoft School of Medicine Wright State University Dayton OH

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

3. Dementia-Associated Behavioral Symptoms: Why are recognition, assessment, treatment, and monitoring so complicated?

4. New slides from the National Nursing Home Survey

5. 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.

6. 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

7. 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.

8. 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.

9. 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

10. 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.

11. 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.

12. Surveyor view… • Provider view… • Different versions of the truth?

13. 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?

14. 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?

15. 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)

16. 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.

17. 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.

18. 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.

19. Show of hands.

20. AAPs are used to treat dementia-associated behavioral symptoms in nursing facility residents. • Agree • Disagree • Neither agree nor disagree

21. AAPs are over-used in the treatment of dementia- associated behavioral symptoms in nursing facility residents. • Agree • Disagree • Neither agree nor disagree

22. 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

23. The effectiveness of AAPs in treating dementia-associated behavioral symptoms in nursing facility residents is over-rated. • Agree • Disagree • Neither agree nor disagree

24. The danger of AAPs in treating dementia- associated behavioral symptoms in nursing facility residents is over-stated. • Agree • Disagree • Neither agree nor disagree

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

26. 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 .

27. 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 .

28. 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.

29. 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.

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

31. 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.

32. 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.

33. 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.

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

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

36. 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.

37. 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.

38. 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.”

39. 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.

40. 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).

41. 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.

42. 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.

43. 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.

44. … requires ongoing respectful dialogue!

45. The Michigan Department of Community Health

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

48. Were behaviors characterized in enough detail (onset, trigger, nature, intensity, duration, frequency, consequences, and other relevant information)?

49. Was there documentation that justified why the behavior was considered problematic?

50. Was there timely recognition of problematic behavior?