A symposium entitled “Progress in Mental Illness 2002: Advances in Psychotherapeutics for the Elderly” was recently conducted. The presentations focused on the management and Quality Indicators involved in the long-term care of elderly patients with dementia, specifically with regard to issues concerning agitation and aggression.

CME ACCREDITED PROGRAM
EDUCATIONAL OBJECTIVES
• Cite the prevalence of behavioral disturbances among patients with agitation and aggression.
• Describe the role environment plays in the treatment of aggression in long-term care settings.
• Discuss the use of antipsychotics in the elderly.
• Summarize the new regulatory guidelines and their utilization in the long-term care setting.
• Explain the impact of Quality Indicators as new standards of care.


Symptom-Based Approach to the Treatment of Agitation and Aggression

Soo Borson, MD, Professor of Psychiatry and Behavioral Sciences and Director of Geropsychiatry Services, University of Washington Medical Center, Seattle, discussed neurodegenerative diseases and other factors that lead to agitation and aggression in the elderly. She also presented a symptom-based approach to treatment of these distressing behavioral problems.

Causes of Agitation and Aggression
Factors that can lead to aggression in elderly patients include environmental issues, delirium, medications, and direct effects of neurodegenerative diseases.

Environmental issues
Behavioral disturbance often results from the exposure of a patient with a vulnerable (old or damaged) brain to an unhealthy environment. While aggression can occur in response to insensitive personal care or physical discomfort, “emotional contagion” between patient and caregiver should also be considered. Patients with dementia may respond behaviorally to their caregivers’ emotional tone. “If interactions between nurses’ aides and patients are not optimal, provision of personal care can prompt aggressive behavior that might otherwise not occur,” said Dr. Borson. Improved interpersonal exchanges can be achieved through teaching and modeling of good clinical practice.

Delirium
Agitation is a common symptom of delirium. Delirium in nursing homes is most often precipitated by an acute infection or reaction to a medication. “The majority of aggressive outbursts that occur in long-term care are contributed by a small proportion of individuals, often with acute illnesses such as recurrent urinary tract infections or other medical problems that are manifested behaviorally,” Dr. Borson explained.

Medications
Any drug that affects the central nervous system can potentially be associated with behavioral changes. Medications with anticholinergic properties are of particular concern.

Neurodegenerative diseases
“Neurodegenerative diseases are the most common causes of agitation and aggression across the board in older adults,” said Dr. Borson. These include Alzheimer’s disease, stroke, vascular dementia, Lewy body dementia, and frontal lobe dementias, as well as rarer disorders.

Prevalence of Irreversible Dementias
Alzheimer’s disease is the most common form of dementia, followed by vascular dementia and Lewy body dementia.1,2 Late-onset frontotemporal dementia is also gaining greater recognition in the United States (Figure 1).3

Alzheimer’s disease
Lyketsos et al4 reported on the prevalence of behavioral problems in 329 patients with dementia ascertained in the population-based Cache County Study. Validated behavioral rating scales were used. Agitation and aggression occurred in 24% of patients. Delusions and hallucinations occurred at rates of 19% and 14%, respectively. In previous studies conducted in clinical, neurologic, and psychiatric settings, 30-90% of Alzheimer’s patients were affected by agitation, aggression, and/or psychosis.5,6

The prevalence of agitation and aggression in Alzheimer’s disease begins to rise early in the course, and peaks 6-8 years after onset. As a result, Alzheimer’s disease patients are most likely to become aggressive when their disease reaches a moderate to severe level. However, as the disease further progresses, the degrees of agitation and aggression wane as patients become more cognitively impaired and behaviorally less capable.

Clinical correlates associated with agitation and aggression in Alzheimer’s disease patients include psychosis, hallucinations, and delusions of persecution, abandonment, or invasion of personal space.7-9 Depression and anxiety are other common psychopathologic concomitants of agitation and aggression in this population.10-13 Sleep disorders affect 13-33% of Alzheimer’s disease patients.14 Evidence is emerging that patients with sleep disturbances are likely to be agitated during the day.

Other clinical correlates of agitation and aggression in Alzheimer’s disease include neurologic signs, specifically extrapyramidal signs. Parkinson-like rigidity and bradykinesia occur in 63.5% of Alzheimer’s disease patients, tested with a very sensitive measure, and this finding is associated with agitation and aggression.15 The presence of two or more painful conditions from any cause is also associated with agitation and/or aggression.16

The neuroanatomical changes associated with these types of behavioral alterations in dementia are just beginning to be understood. Sultzer and colleagues17 used positron emission tomography (PET) to study glucose metabolism in the brain and found that psychosis is associated with frontal lobe hypometabolism while agitation correlates with frontal and temporal changes. Kotrla et al18 used single photon emission computer tomography (SPECT) to study patterns of brain perfusion and found that any delusions or hallucinations in patients with mild-to-moderate Alzheimer’s disease were associated with specific regional impairments. Delusions were associated with frontal impairments; left-sided hypoperfusion was more predictive than right-sided hypo¬perfusion. Hallucinations were associated with parietal lobe hypoperfusion. While the complexities of both neuroimaging and behavioral assessment make studies relating the two difficult, there is reason to hope that a behavioral map of the brain in Alzheimer’s disease and other dementias may eventually be used to predict outcome and response to treatment.

Stroke
There are some clinical predictors of behavioral dyscontrol (ie, agitation or aggressive outbursts) in stroke patients. According to Kim and associates,19 who studied 145 patients 3-12 months after having a stroke, these predictors included the presence of motor impairment, dysarthria, communication deficit due to impaired language production, and emotional incontinence. Stroke locations were associated specifically with this form of behavioral disturbance.

Frontal lobe dementia
Mychack et al20 used SPECT to study brain perfusion patterns and identified which frontal lobe was more affected in 41 patients with frontal lobe dementia. Although only 29% of the patients had right-predominant disease, 11 of the 12 patients with right-sided frontal lobe dementia had socially undesirable behavior as an early presenting symptom (eg, criminal behavior, aggression, loss of job, alienation from family/friends, financial recklessness, sexually deviant behavior, or abnormal response to spousal crisis). Patients with left-sided predominance were much less likely to have this kind of behavioral disturbance (2 of 19 patients).

Pharmacotherapy
Agitation and aggression in elderly patients with dementia can be treated with acetylcholinesterase inhibitors, atypical antipsychotics, and certain other agents. Evidence-based guidelines are available for the use of such medications under these circumstances.

Acetylcholinesterase inhibitors
Acetylcholinesterase inhibitors promote behavioral improvement. “They set the platform on which the remaining interventions for behavioral disturbance are built,” Dr. Borson explained. All acetylcholinesterase inhibitors have the same general effect: they improve and/or stabilize behavior.

Because the highest prevalence of agitation and aggression occurs when the disease is fairly advanced (6-8 years after diagnosis), it is important to consider the effect any intervention will have on disease progression. Acetylcholinesterase inhibitors can slow the progression of clinical decline, although they cannot stop it. Acetylcholinesterase inhibitors currently in use include donepezil, rivastigmine, and galantamine.

Donepezil. Donepezil was the first acetylcholinesterase inhibitor to be widely used in treating Alzheimer’s disease. This drug has been studied in mild, moderate, and severe dementia. Winblad et al21 conducted a one-year, randomized, multicenter, placebo-controlled, double-blind, outpatient study of donepezil in 286 patients with mild-to-moderate Alzheimer’s disease (mean Mini-Mental State Examination [MMSE] = 19; range, 10-26). The dosage used in the donepezil treatment group was 5 mg/day for the first 28 days followed by 10 mg/day for the remainder of the trial. The mean patient age was 72.5 years. While both patient groups continued to decline, the donepezil-treated patients declined half as quickly compared to the placebo-treated patients as measured by the Progressive Deterioration Scale (a global rating of behavior, cognition, and function).

Feldman and colleagues22 reported results of a 6-month, randomized, double-blind, placebo-controlled study of donepezil in 290 nursing home patients with moderate-to-severe Alzheimer’s disease (mean MMSE = 11.7; range, 5-17). Patients were treated with donepezil 5 mg/day for the first 28 days followed by 10 mg/day for the remainder of the trial. The mean patient age was 73.6 years, and 80% of patients completed the study. The Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC-plus) scale was used for assessment. Although both the placebo and treatment groups demonstrated behavioral improvements even in advanced dementia, the outcome favored active drug treatment, and the results were significant. Patients who did not require psychotropic medications at baseline (ie, patients who were less behaviorally impaired at entry) experienced greater improvement. Depression, dysphoria, anxiety, and apathy were the most responsive symptoms.

A 6-month, randomized, placebo-controlled, double-blind trial of donepezil was conducted by Tariot et al23 in 208 nursing home patients with mild-to-severe Alzheimer’s disease with or without cerebrovascular disease (mean MMSE = 14.4; range, 5-26). The mean patient age was 85.7 years, and 80% of patients completed the study. The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Cognition and function stabilized or improved with donepezil-treated patients and declined in placebo-treated patients. Behavioral improvements were found in both the placebo and treatment groups, with no differences between the groups.

Rivastigmine. Cummings and associates24 conducted a 26-week, prospective, open-label, multicenter study of the effect of rivastigmine (3-12 mg/day) on behavior in nursing home patients with probable Alzheimer’s disease (MMSE range, 6-15). They utilized the NPI-NH to determine improvements in behavior. There were numerous behavioral impairments present at baseline, many of which improved significantly with rivastigmine treatment.

A 96-week, open-label trial of rivastigmine (3-12 mg/day) was carried out in 29 patients with diffuse Lewy body dementia, of which 20 completed the study.25 According to the MMSE and NPI-NH scales, rivastigmine improved both cognition and behavior scores during the first 24 weeks, but by the end of the study, neither the MMSE nor the NPI-NH scores were significantly different from baseline scores.

Galantamine. Galantamine is the newest of the acetylcholinesterase inhibitors and appears to have a behavior-stabilizing effect. Tariot et al26 conducted a 5-month, randomized, double-blind, placebo-controlled, multicenter trial of two doses of galantamine (16 and 24 mg/day) in 978 patients with mild-to-moderate Alzheimer’s disease. Using the CIBIC-plus scale, a global rating by the clinician and caregiver, the study found a stabilization of behavior from baseline in both treatment groups. In comparison, the patients taking placebo experienced a behavioral deterioration.

Erkinjuntti and colleagues27 conducted a 6-month, multicenter, randomized, placebo-controlled, double-blind trial of the effect of galantamine (24 mg/day) on behavior in 592 patients with vascular dementia with or without Alzheimer’s disease. Galantamine was effective in improving behavior according to the CIBIC-plus scale while the placebo group scores continued to decline.

Antipsychotic agents
When agitated behavior is severe and aggression is involved, acetylcholinesterase inhibitors are unlikely to be effective as the sole pharmacologic intervention. Other psychotropic medications such as atypical antipsychotics are often required. Olanzapine, risperidone, and other atypical antipsychotics, as well as haloperidol, have all been or are being studied in the treatment of agitation, psychosis, and aggressive behavior in dementia.

Olanzapine. A 6-week, randomized, double-blind, placebo-controlled trial was conducted to determine the effect of three different doses of olanzapine (5, 10, or 15 mg/day) on agitation or aggression in 206 nursing home patients with dementia.28 Patients were assessed using the NPI-NH scale. The most effective doses were found to be 5 mg and 10 mg. There was less improvement in patients taking 15 mg olanzapine, which did not separate from placebo, perhaps because of toxicity issues. Olanzapine was found to be an effective agent for treatment of agitation and aggression in long-term care patients with dementia (Figure 2).

There are some extrapyramidal side effects associated with olanzapine, but no reported cases of tardive dyskinesia. However, somnolence can be a problem, and some patients do not tolerate fully effective doses because they become oversedated and tend to develop gait impairment.28

Risperidone. Pooled data from three 12-week phase III trials of risperidone were presented by Dr. Borson. Roughly similar protocols were used in all studies. In total, 1150 elderly nursing home or institutionalized patients were given either risperidone or placebo. The median age for the study was 82 years, and at least 80% of patients were over 75 years old. Patients had mixed diagnoses: 69% of patients had Alzheimer’s disease, 11% had Alzheimer’s plus vascular dementia, and 20% had vascular dementia. All patients had been afflicted with chronic behavioral symptoms for an average of three years at entry into the study.29

The researchers used the Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD) and its psychosis subscale to determine the effect on behavior. The BEHAVE-AD scale showed significant improvement in risperidone-treated patients when compared to placebo (Figure 3).29

The Cohen-Mansfield Agitation Inventory was also used in these studies to determine the effect of risperidone on various forms of agitation, and showed significant improvements in the risperidone-treated group when compared to placebo (Figure 4).29 There was a better response of the agitation cluster than of the psychosis cluster in these pooled studies.

In terms of side effects, risperidone is a safe drug for the elderly, with somnolence and extrapyramidal symptoms only occurring at higher doses (2 mg/day).30 The incidence of tardive dyskinesia was studied by Jeste and associates31 in a 9-month, prospective, longitudinal comparison of risperidone versus haloperidol. Sixty-one outpatients with schizophrenia, schizoaffective disorder, and/or dementia were placed in each of the risperidone and haloperidol groups. These groups were matched for median dose (1 mg/day) and duration of exposure. The mean patient age was relatively young at 66 years. Haloperidol, in keeping with previous studies, caused tardive dyskinesia in much higher percentages than risperidone. Jeste et al32 conducted a larger, one-year, open-label extension trial that examined the incidence of tardive dyskinesia in 255 patients with dementia who were given flexible doses of risperidone (mean dose 0.96 mg/day) for a mean total duration of 273 days. All patients were free of dyskinesia at the beginning of the study, and their mean age was 82.5 years. The Extrapyramidal Symptom Rating Scale was used for assessment. By the end of the extension trial, incident tardive dyskinesia was found to have occurred in only 2.6% of risperidone-treated patients, which is approximately 10-fold less than that observed with conventional antipsychotics.31

Other atypical antipsychotics. Clozapine, the earlier atypical antipsychotic, is generally not indicated for the treatment of dementia-related neuropsychiatric disorders, except in special cases of Lewy body or Parkinson’s dementia. More data are required to determine whether the other atypical antipsychotics (quetiapine, ziprasidone) are effective in treating agitation and aggression in dementia. Data are slowly beginning to emerge regarding efficacy and indications for quetiapine, but more studies are needed in geriatric populations. Similarly, there are limited data to support ziprasidone, specifically in geriatric patients, until further studies have been conducted.

Other agents. Other drugs, such as mood-stabilizing anticonvulsants, serotonin modulators, beta-adrenergic blockers, and antiandrogenic agents, can also be effective in selected patients. These drugs are not as well studied, and none are Food and Drug Administration (FDA)-approved for the indication of agitation, psychosis, or aggression in dementia.

Evidence-Based Recommendations for the Treatment of Agitation or Psychosis in Dementia
The first important point in the evidence-based recommendations for treating agitation or psychosis in dementia is that “antipsychotic agents should be used to treat agitation or psychosis when environmental intervention fails,” urged Dr. Borson.33 “This, of course, implies that environmental intervention should be employed first.” Successful environmental intervention can be implemented with the creation and adoption of specific protocols.

Second, the recommendations state that atypical antipsychotics may be better tolerated than traditional neuroleptics such as haloperidol. Third, agitation associated with other neurobehavioral syndromes may require different treatments.33

References
1. Guttman R, Altman RD, Nielsen NH. Alzheimer disease: Report of the Council on Scientific Affairs. Arch Fam Med 1999;8:347-353.
2. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): Report of the Consortium on DLB International Workshop. Neurology 1996;47:1113-1124.
3. Cherrier MM, Mendez MF, Perryman KM, et al. Frontotemporal dementia versus vascular dementia: Differential features on mental status examination. J Am Geriatr Soc 1997;45:579-583.
4. Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental and behavioral disturbances in dementia: Findings from the Cache County Study on Memory in Aging. Am J Psychiatry 2000;157:708-714.
5. Patterson MB, Schnell AH, Martin RJ, et al. Assessment of behavioral and affective symptoms in Alzheimer’s disease. J Geriatr Psychiatry Neurol 1990;3:21-30.
6. Burns A, Jacoby R, Levy R. Behavioral abnormalities and psychiatric symptoms in Alzheimer’s disease: Preliminary findings. Int Psychogeriatr 1990;2:25-36.
7. Rapoport MJ, van Reekum R, Freedman M, et al. Relationship of psychosis to aggression, apathy and function in dementia. Int J Geriatr Psychiatry 2001;16:123-130.
8. Deutsch LH, Bylsma FW, Rovner BW, et al. Psychosis and physical aggression in probable Alzheimer’s disease. Am J Psychiatry 1991;148:1159-1163.
9. Aarsland D, Cummings JL, Yenner G, Miller B. Relationship of aggressive behavior to other neuropsychiatric symptoms in patients with Alzheimer’s disease. Am J Psychiatry 1996;153:243-247.
10. Hwang JP, Tsai SJ, Yang CH, et al. Persecutory delusions in dementia. J Clin Psychiatry 1999;60:550-553.
11. Chemerinski E, Petracca G, Manes F, et al. Prevalence and correlates of anxiety in Alzheimer’s disease. Depress Anxiety 1998;7:166-170.
12. Kunik ME, Snow-Turek AL, Iqbal N, et al. Contribution of psychosis and depression to behavioral disturbances in geropsychiatric inpatients with dementia. J Gerontol A Biol Sci Med Sci 1999;54:M157-M161.
13. Lyketsos CG, Steele C, Galik E, et al. Physical aggression in dementia patients and its relationship to depression. Am J Psychiatry 1999;156:66-71.
14. Vitiello MV, Borson S. Sleep disturbances in patients with Alzheimer’s disease: Epidemiology, pathophysiology and treatment. CNS Drugs 2001;15:777-796.
15. Caligiuri MP, Peavy G. An instrumental study of the relationship between extrapyramidal signs and psychosis in Alzheimer’s disease. J Neuropsychiatry Clin Neurosci 2000;12:34-39.
16. Feldt KS, Warne MA, Ryden MB. Examining pain in aggressive cognitively impaired older adults. J Gerontol Nurs 1998;24:14-22.
17. Sultzer DL, Mahler ME, Mandelkern MA, et al. The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer’s disease. J Neuropsychiatry Clin Neurosci 1995;7:476-484.
18. Kotrla KJ, Chacko RC, Harper RG, et al. SPECT findings on psychosis in Alzheimer’s disease. Am J Psychiatry 1995;152:1470-1475.
19. Kim JS, Choi S, Kwon SU, Seo YS. Inability to control anger or aggression after stroke. Neurology 2002;58:1106-1108.
20. Mychack P, Kramer JH, Boone KB, Miller BL. The influence of right frontotemporal dysfunction on social behavior in frontotemporal dementia. Neurology 2001;56(suppl 4):S11-S15.
21. Winblad B, Engedal K, Soininen H, et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57:489-495.
22. Feldman H, Gauthier S, Hecker J, et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology 2001;57:613-620.
23. Tariot PN, Cummings JL, Katz IR, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer’s disease in the nursing home setting. J Am Geriatr Soc 2001;49:1590-1599.
24. Cummings J, Anand R, Koumaras B, et al. Rivastigmine provides behavioral benefits to Alzheimer’s disease patients residing in a nursing home: Findings from a 26-week trial. Neurology 2000;54(suppl 3):A468.
25. Grace J, Daniel S, Stevens T, et al. Long-term use of rivastigmine in patients with dementia with Lewy bodies: An open-label trial. Int Psychogeriatr 2001;13:199-205.
26. Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD: The Galantamine USA-10 Study Group. Neurology 2000;54:2269-2276.
27. Erkinjuntti T, Kurz A, Gauthier S, et al. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: A randomised trial. Lancet 2002;359:1283-1290.
28. Street JS, Clark WS, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer’s disease in nursing care facilities: A double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry 2000;57:968-976.
29. Janssen Pharmaceutica (data on file).
30. Katz IR, Jeste DV, Mintzer JE, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: A randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry 1999;60:107-115.
31. Jeste DV, Lacro JP, Bailey A, et al. Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients. J Am Geriatr Soc 1999;47:716-719.
32. Jeste DV, Okamoto A, Napolitano J, et al. Low incidence of persistent tardive dyskinesia in elderly patients with dementia treated with risperidone. Am J Psychiatry 2000;157:1150-1155.
33. Doody RS, Stevens JC, Beck C, et al. Practice parameter: Management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1154-1166.


Converting the “Clinical” Into the “Practical”: Improving Quality of Life in Elderly Patients

Malcolm Fraser, MD, CMD, President, Bay Geriatrics/Synergy Health Solutions, St. Petersburg, FL, provided an in-depth discussion on effective ways to improve upon Quality Indicators and the new Consumer Quality Measures in the nursing home setting.

The Minimum Data Set
In nursing homes, every patient is assessed using the Minimum Data Set (MDS). The MDS is a “complete description” of the nursing home patient and evaluates the condition of the bowels, bladder, cognition, skin, and other important variables. The MDS was introduced by the Omnibus Budget Reconciliation Act of 1987 (OBRA ‘87), and is completed by a designated nurse who is usually an employee of the nursing home. MDS results for all patients within a nursing home are reported to the Centers for Medicare and Medicaid Services (CMS; formerly called the Health Care Financing Administration [HCFA]). In turn, CMS determines the amount of funding to be provided to the nursing home for caring for Medicare Part A patients covered under the Prospective Payment System.

Quality Indicators
Some of the information in the MDS is fed back to the nursing homes as Quality Indicators. Quality Indicators were initially introduced into nursing homes, but will eventually be used in most aspects of health care where the federal government is the payor.

For the last three years, there have been 24 Quality Indicators divided into 11 categories: accidents, behavioral problems, clinical management, cognitive patterns, elimination (incontinence), infection control, nutrition, physical functioning, psychotropic drug use, quality of life, and skin care. The aim is to reach below the 90th percentile in all categories when compared to other similar institutions.

Accidents, namely falls and fractures, are of particular importance because up to two-thirds of lawsuits against nursing homes and one-quarter of lawsuits against hospitals relate to injuries from falls.1 Anything that can be done to reduce the likelihood of falls should be implemented.

Behavioral problems include behavioral or emotional symptoms that affect others, and depression with or without antidepressant therapy. The presence of cognitive impairment is another concern. In terms of clinical management of medication, issues arise if a patient is prescribed nine or more medicines at one time, if antipsychotic drugs are used without indication, or if hypnotics are utilized more than twice a week.

Elimination problems are comprised of bowel or bladder incontinence, incontinence without a toileting plan, the presence of an indwelling catheter, or fecal impaction. Infection control issues include the presence of urinary tract infections. Nutritional problems can involve weight loss, tube feeding, or dehydration.

Physical functioning issues include being confined to bed and experiencing a decline in activities of daily living or range of motion. Quality-of-life concerns encompass daily physical restraints and little or no activity. Skin care problems involve stage 1-4 pressure ulcers.
There are also three sentinel events: dehydration, fecal impaction, and pressure ulcers. Sentinel events can be thought of as zero tolerance. A facility may be below the 90th percentile, but a single sentinel event can cause a concern.

Medications With Anticholinergic Effects
Many of the Quality Indicator symptoms are similar to the effects produced by anticholinergic drugs. In addition, medications with anticholinergic effects may cause delirium, delusions, hallucinations, and agitation.2 Some anticholineric action of varying clinical significance has been noted with the following medications: cimetidine, prednisolone, theophylline, digoxin, furosemide, ranitidine, nifedipine, isosorbide, warfarin, dipyridamole, codeine, triamterene, hydrochlorothiazide, and captopril. These effects are cumulative and may be clinically relevant.3 “If a patient presents with the possibility of Alzheimer’s disease, the first order of business is make sure the patient is not taking any medicines with anticholinergic side effects,” said Dr. Fraser.

Certain psychotropic medications have anticholinergic effects. These include tricyclic antidepressants (amitriptyline, doxepin, and imipramine), certain antipsychotics (thioridazine, chlorpromazine, clozapine, and olanzapine), and diphenhydramine. Medications causing anticholinergic effects should be stopped in all patients who need to take acetylcholinesterase inhibitors.

Side Effects Associated With Typical Antipsychotics
Predictable side effects, such as extrapyramidal symptoms, anticholinergic side effects, cognitive toxicity, sedation, orthostatic hypotension, and tardive dyskinesia are associated with conventional or typical antipsychotic agents such as haloperidol and thioridazine.3 Patients taking typical antipsychotics also experience high levels of confinement to bed, decline in function, contractures, constipation, and decubitus ulcers. Fortunately, the chronic use of these agents continues to decline, and they currently are only prescribed in 5% of patients.

Benefits of Atypical Antipsychotics
Newer atypical antipsychotic agents are commonly used in long-term care because they are more effective than the typical agents and have fewer side effects. Atypical agents include clozapine, olanzapine, risperidone, quetiapine, and ziprasidone. Richelson4 compared all of these agents (except ziprasidone, for which there are no data in long-term patients over the age of 65, and for which use in nursing homes has shown to be negligible thus far) in terms of their likelihood to cause histamine H1 receptor blockade side effects (eg, sedation and weight gain). Risperidone and quetiapine were shown to have the least amount of antihistamine side effects (Figure 5), and caused the least amount of anticholinergic effects (Figure 6). “It is not possible to overemphasize the importance of antihistamine and anticholinergic side effects. So be vigilant with regard to the potential side effects of medications,” Dr. Fraser urged.

Summary
Psychosis and agitation are common in the elderly. It is important to make sure that there is no physical reason for agitation in patients, such as medical disorders, physical discomfort, or certain medications, as well as no pharmacologic reason for cognitive impairment, such as anticholinergic side effects. Specific atypical antipsychotics such as risperidone have demonstrated efficacy and safety in the elderly, with minimal antihistamine and anticholinergic side effects. The emergence of atypical agents over the last five years marks the beginning of a new era in the pharmacologic treatment of agitation and aggression in the elderly.

References
1. St. Paul Insurance Company Annual Long-Term Care Report, 1997.
2. Schneider LS. Pharmacologic management of psychosis in dementia. J Clin Psychiatry 1999;60(suppl 8):54-60.
3. Tune L, Carr S, Hoag E, Cooper T. Anticholinergic effects of drugs commonly prescribed for the elderly: Potential means for assessing risk of delirium. Am J Psychiatry 1992;149:1393-1394.
4. Richelson E. Receptor pharmacology of neuroleptics: Relation to clinical effects. J Clin Psychiatry 1999;60(suppl 10):5-14.

CME ACCREDITATION & INSTRUCTIONS
Progress in Mental Illness: Advances in Psychotherapeutics for the Elderly
This activity was developed for primary care physicians and geriatric psychiatrists.

Accreditation
• The American Association for Geriatric Psychiatry (AAGP) is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
• AAGP designates this continuing medical education activity for one credit hour in Category 1 of the Physician’s Recognition Award of the American Medical Association. Each physician should claim only those hours of credit he/she actually spent in the educational activity.
• This CME activity was planned and produced in accordance with the ACCME Essentials.
• Based upon trials, the estimated time to complete this program is one hour.
Instructions
A certificate of completion will be awarded to physicians completing the post–test and evaluation form. Please complete the program evaluation and mail it to:

American Association for Geriatric Psychiatry
7910 Woodmont Ave
Suite 1050
Bethesda, MD 20814-3004
Please allow three weeks for processing. Program expiration date is October 2003. Please phone (301) 654-7850 or fax (301) 654-4137 with any questions.

Educational Objectives
Upon completion of this program, participants should be able to:
• Cite the prevalence of behavioral disturbances among patients with agitation and aggression.
• Describe the role environment plays in the treatment of aggression in long-term care settings.
• Discuss the use of antipsychotics in the elderly.
• Summarize the new regulatory guidelines and their utilization in the long-term care setting.
• Explain the impact of Quality Indicators as new standards of care.

CME EVALUATION
Please circle the number that best reflects your opinions on the following statements, using the following rating scale:
1 = Strongly Agree; 2 = Agree; 3 = Disagree; 4 = Strongly Disagree.

1. The program objectives were met. 1 2 3 4
2. The program content was useful. 1 2 3 4
3. The program content was relevant. 1 2 3 4
4. The program was educational. 1 2 3 4
5. The program was not promotional. 1 2 3 4

Additional Comments:



CME EXAM—INSTRUCTIONS

Progress in Mental Illness: Advances in Psychotherapeutics for the Elderly
A certificate of completion will be awarded to physicians completing the post-test and evaluation form. Please complete the following examination sheet and mail it to:

American Association for Geriatric Psychiatry
7910 Woodmont Ave
Suite 1050
Bethesda, MD 20814-3004

Please allow three weeks for processing. Program expiration date is October 2003. Please phone (301) 654-7850 or fax (301) 654-4137 with any questions.

1. Agitation and aggression are often caused by:
a. Alzheimer’s disease
b. Frontal lobe dementia
c. Vascular dementia
d. All of the above
e. None of the above


2. Agitation and aggression in Alzheimer’s disease peak:
a. Within the first year of diagnosis
b. 2-3 years after diagnosis
c. 4-6 years after diagnosis
d. 6-8 years after diagnosis
e. Never; they continue to progress with the disease


3. Any drug that affects the central nervous system can be associated with behavioral changes.
a. True
b. False


4. Patterns of altered brain metabolism and perfusion are associated with psychosis in Alzheimer’s disease.
a. True
b. False


5. If a patient with frontal lobe deficits shows socially undesirable behavior as early presenting symptoms, he/she will more likely have:
a. Right-sided frontal lobe dementia
b. Left-sided frontal lobe dementia
c. Lewy body dementia
d. Vascular dementia


6. Acetylcholinesterase inhibitors can improve or stabilize behavior and slow the progression of clinical decline because they reduce the severity of neuropathologic change.
a. True
b. False


7. The incidence of tardive dyskinesia in patients taking risperidone is:
a. 10-fold greater than olanzapine
b. 10-fold less than olanzapine
c. 10-fold less than haloperidol
d. 10-fold greater than haloperidol


8. A facility should aim to reach above the 90th percentile in all Quality Indicator categories.
a. True
b. False


9. The three sentinel events in the Quality Indicator system are dehydration, fecal incontinence, and pressure ulcers.
a. True
b. False


10. Atypical antipsychotic medications that appear to have the least amount of antihistamine and anticholinergic side effects are:
a. Clozapine and olanzapine
b. Olanzapine and quetiapine
c. Olanzapine and risperidone
d. Quetiapine and risperidone
e. None of the above


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The American Association for Geriatric Psychiatry requires that the authors participating in a continuing medical education activity disclose to participants any significant financial interest or other relationship (1) with the manufacturers of any commercial service discussed in an educational presentation, and (2) with any commercial supporters of the activity. Dr. Borson reported the following: she has served as a consultant for Janssen Pharmaceutica and Forest Pharmaceuticals; she receives grants and research support from Forest Pharmaceuticals and Pfizer; she is on the speaker’s bureau of Janssen Pharmaceutica, Forest Pharmaceuticals, Pfizer, Organon, and Wyeth Pharmaceuticals. Dr. Fraser has reported the following: he is a consultant for Janssen Pharmaceutica; he is on the speaker’s bureau of Janssen Pharmaceutica, Merck & Co, and Organon.

This special report was sponsored by the American Association for Geriatric Psychiatry and produced by MultiMedia HealthCare/Freedom, LLC, under an unrestricted educational grant from Janssen Pharmaceutica. The views expressed in this publication are not necessarily those of Janssen Pharmaceutica or the publishers. This publication may not be reproduced in whole or in part without the express written permission of MultiMedia HealthCare/Freedom, LLC.

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