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Dementia and Psych Meds

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1 Dementia and Psych Meds
Andrew S. Rosenzweig, MD, MPH Medical Director, MedOptions Assistant Clinical Professor, Brown University

2 What Is A Geriatric Psychiatrist?
A geriatric psychiatrist is a medical doctor with special training in the diagnosis and treatment of mental disorders that may occur in older adults. These disorders include, but are not limited to, dementia, depression, bipolar disorder, anxiety and late-life schizophrenia.

3 Demographics of the Elderly Population
By 2030, older adults will account for 20% of the population, up from 13% in 2000 At age 85+, there are 241 women for every 100 men Mental disorders in older adults are under-reported The rate of suicide is highest among older adults compared to any other age group

4 Most Common Psychiatric Disorders in Late Life
Outpatient Dementia Depression Substance Abuse (alcohol) Psychotic Disorders Long-Term Care Dementia Other Organic Mental Disorders Mood Disorders MR-DD Psychotic Disorders

5 Alzheimer’s Disease (AD): More Than Just Memory Loss
AD is a progressive, degenerative disease involving: Loss of memory and other cognitive functions Decline in ability to perform activities of daily living Changes in personality and behavior Increases in resource utilization Eventual nursing home placement AD affects all aspects of life for both the patient and the caregiver

6 “A Peculiar Disease of the Cerebral Cortex”
Alzheimer’s Original Case Report (1907) The first case report of Alzheimer’s disease highlighted the presence of psychosis and agitation in these patients “The first noticeable symptom of illness was suspiciousness of her husband…believing that people were out to murder her” “She screams that her doctor wants to cut her open; at times, she seems to have auditory hallucinations” “A Peculiar Disease of the Cerebral Cortex” Alzheimer’s Original Case Report (1907) We often focus on the cognitive symptom domain of dementing illnesses such as AD. However, for the patient described in the first published case report of AD, behavioral and psychotic symptoms caused greater disability than cognitive changes. This finding has been corroborated in subsequent studies, illustrating that dementia is more than a disorder of cognition: it is also a psychiatric illness Psychiatric symptoms, such as psychosis (delusional thought content, paranoia, hallucinations), agitated and aggressive behavior, depression, and sleep/wake cycle reversal, are common in patients with dementia. These behavioral disturbances are a significant cause of caregiver stress and of premature institutionalization of patients with dementia Source: Alzheimer A. Allegmeine Zeitschrift für Psychiatrie. 1907;64: Alzheimer A. Uber eine eigenartige Erkraukung der Hirwrinde. Allegmeine Zeitschrift für Psychiatrie. 1907;64: Aronson SM. Treatment of behaviorally disturbed elderly patients: a clinical approach. In: Brunello N, Langer SZ, Racagni G, eds. Mental Disorders in the Elderly: New Therapeutic Approaches, Vol 13. Basel, Switzerland: S Karger AG; 1998:

7 Behavioral and Psychological Symptoms of Dementia
Psychosis Delusions Paranoia Hallucinations Agitation Aggression Combativeness Hyperactivity (including wandering) Hypervocalization Disinhibition Behavioral and Psychological Symptoms of Dementia Symptoms Participants at the IPA consensus conference felt that behavioral and psychological symptoms of dementia could be conveniently grouped into 2 categories: Symptoms that are primarily assessed on the basis of interviews with patients and/or relatives. These symptoms may be associated with psychotic behaviors and may include delusions, paranoid ideation, and hallucinations Symptoms associated with agitation that are usually identified on the basis of observation of patient behavior. These may include aggression, combativeness, hyperactivity including wandering, screaming, sexual disinhibition, or culturally inappropriate behaviors Source: Finkel et al. Am J Geriatr Psychiatry. 1998;6: Finkel SI, Costa e Silva J, Cohen GD, et al. Behavioral and psychological symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Am J Geriatr Psychiatry. 1998;6:

8 Behaviors Reported in Agitation and Aggression
Physical: pacing, inappropriate robing/disrobing, trying to get to a different place, handling things inappropriately, restlessness, stereotypy Verbal: Complaining, requests for attention, negativism, repeated questions/phrases, screaming Aggression Physical: hitting, kicking, pushing, scratching, tearing, biting, spitting Verbal: threats, accusations, name-calling, obscenities It’s a good idea to take the next step in classifying agitation and aggression, this time by separating each into physical and verbal components. This is important as you’ll see later when we talk about target symptoms and management.

9 Psychosis and Agitation: What We Know
Common in Alzheimer’s disease and other dementing illnesses Major source of caregiver distress Contribute to Premature institutionalization Increased cost Psychosis and Agitation: What We Know Psychosis and/or agitation are common in the course of dementia, occurring in a majority of cases. In patients with dementia, the overall incidence of psychosis is estimated to be 34% to 50% and agitation 60% to 80%. Patients can experience delusions, hallucinations, and agitated behavior at any point in the course of their illness Behavior changes are a major source of distress to caregivers and lead to caregiver depression and anxiety, premature institutionalization, and increased cost of care Sources: Drevets et al. Biol Psychiatry. 1989;25:39-48./Ellgring. Neurology. 1999:52(suppl 3):S17-S20./Rabins PV. Int Psychogeriatr. 1991;3: Drevets WC, Rubin EH. Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biol Psychiatry. 1989;25:39-48. Ellgring JH. Depression, psychosis, and dementia: impact on the family. Neurology. 1999:52(suppl 3):S17-S20. Gormley N, Rizwan MR. Prevalence and clinical correlates of psychotic symptoms in Alzheimer’s disease. Int J Geriatr Psychiatry. 1998;13: Rabins PV. Psychosocial and management aspects of delirium. Int Psychogeriatr. 1991;3:

10 Prevalence of Symptoms of Psychosis and Agitation in Dementia
20 Prevalence of Symptoms of Psychosis and Agitation in Dementia Slide 20 Cache County Study of Memory in Aging (CCSMA) First US population study of behavioral disturbances in dementia Evaluated the prevalence and severity of mental and behavioral disturbances in the elderly 5092 individuals were screened Participants with dementia (n=329) were compared to control group without dementia (n=673) Prevalence of Symptoms of Psychosis and Agitation in Dementia The distribution of mental and behavioral disturbances in the elderly and the association of these disturbances with dementia were investigated in the Cache County Study of Memory in Aging (CCSMA) [Utah], the first US epidemiologic study (2000) to examine behavioral disturbances in Alzheimer’s disease in a community-based population Ninety percent (5092 individuals) of the Cache County population 65 years old were initially screened for dementia with a series of tests that included the Modified Mini-Mental State Examination (MMSE) or the Informant Questionnaire on Cognitive Decline in the Elderly, and the Dementia Questionnaire, along with clinical assessment. Of those, 329 individuals with dementia (65%, Alzheimer’s; 19%, vascular; 16%, mixed) and 673 individuals without dementia (total of 1002 participants) were further rated using the Neuropsychiatric Inventory (NPI) to determine whether they had experienced any of 10 domains in the previous month. Those domains included aberrant motor behavior, agitation, anxiety, apathy, delusions, depression, disinhibition, elation, hallucinations, and irritability Source: Lyketsos CG et al. Am J Psychiatry. 2000;157:

11 Prevalence of Symptoms of Psychosis and Agitation in Dementia
21 Slide 21 Prevalence of Symptoms of Psychosis and Agitation in Dementia The mean age of the participants with dementia was 84.2 ± 7.0 (standard deviation [SD]) years and the mean age of the participants without dementia was 80.8 ± 7.7 SD years In all participants with dementia (n=329), the prevalence of agitation/aggression was 23.7%, delusions 18.5%, and hallucinations 13.7%. Compared to those without dementia, agitation/aggression was 8.5 times more frequent, delusions were 8 times more frequent, and hallucinations were 23 times more frequent in those with dementia Dementia category includes Alzheimer’s dementia and vascular dementia combined Differences were observed in the frequency of behavioral disturbances at different stages of illness. Significant differences occurred in the incidence of agitation/aggression (13%, mild dementia; 24%, moderate dementia; 29%, severe dementia) and in the incidence of aberrant motor behavior (9%, mild dementia; 7%, moderate dementia; 19%, severe dementia) Source: Adapted with permission from Lyketsos CG et al. Am J Psychiatry. 2000;157: American Psychiatric Association.

12 Causes of Distress to Caregivers
Disturbing symptoms Physical violence Catastrophic reactions Hitting Making accusations Suspiciousness Incontinence Memory disturbance Inappropriate sexual behavior Causes of Distress to Caregivers Caregivers, both family at home and staff in extended-care facilities, do not always describe behavioral abnormalities according to physicians’ definitions. When physicians are called, the complaints may be about patients being bothersome, irritable, uncooperative, and intrusive, as well as being aggressive and agitated The widespread nature of this problem was addressed in a study conducted by Rabins. He surveyed 55 caregivers of patients with AD and asked what symptoms were most problematic. Five of the 7 most commonly reported disturbing symptoms were of a behavioral nature. These included physical violence and related behaviors, as well as suspiciousness, making accusations, and hypervocalization Mace NL, Rabins PV. The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer’s Disease, Related Dementing Illness, and Memory Loss in Later Life. Revised. New York: Warner Books; 1992. Rabins PV. Psychosocial and management aspects of delirium. Int Psychogeriatr. 1991;3: Stoppe G, Brandt CA, Staedt JH. Behavioural problems associated with dementia: the role of newer antipsychotics. Drugs Aging. 1999;14:41-54. Sources: Rabins PV. Int Psychogeriatr. 1991;3: /Stoppe et al. Drugs Aging. 1999;14:41-54.

13 Delusions in Alzheimer’s Disease
Delusional thought content (eg, paranoia) is common (studies suggest 34% to 50% incidence) Common delusions Marital infidelity Patients, staff are trying to hurt me Staff, family members are impersonators People are stealing my things My house is not my home Strangers living in my home Misidentification of people People on TV are real Delusions in Alzheimer’s Disease Behavioral agitation in patients with dementia can be caused by delusions and/or confusion. Delusions are especially frequent in dementia, and it is sometimes difficult for the clinician to differentiate between delusion and confusion in these patients. Misidentification of individuals and misplacement of personal belongings are examples Abuse of the elderly and theft are not uncommon. Sometimes there is a basis in reality for these complaints Regardless of the cause of behavioral disturbance in patients with dementia, early intervention with both pharmacologic and nonpharmacologic treatments can alleviate symptoms, improve quality of life, and delay nursing home placement Deutsch LH, Bylsma FW, Rovner BW, et al. Psychosis and physical aggression in probable Alzheimer’s disease. Am J Psychiatry. 1991;148: Drevets WC, Rubin EH. Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biol Psychiatry. 1989;25:39-48. Sources: Deutsch et al. Am J Psychiatry. 1991;148: /Drevets. Biol Psychiatry. 1989;25:39-48.

14 Effect of Losses in Dementia
Normal Feelings Thoughts Behaviors Dementia Feelings Short Circuit Behaviors Thoughts are impaired by losses of: memory of coping with past situations judgment to select among alternative actions insight needed to solve problems inhibitions and impulse control needed to show restraint

15 Practical Recommendations: Decrease Escalation
Approach in a calm manner Use distraction: food, drink, music Maintain eye contact and comfortable posture Match verbal and non-verbal signals Identify and state the affect observed in the patient Identify what is triggering the behavior Modify the environment

16 Target Symptoms for Treatment
Physical aggression Agitation Delusions/paranoia Hallucinations Sleep/wake cycle changes Depression, withdrawal Eating problems Verbal outbursts Target Symptoms for Treatment The reason for initiating drug therapy must be clearly defined at the outset, and the desired management goals must be identified and communicated to the patient’s family and staff on all shifts Written description of target behaviors in the patient’s chart at baseline will provide a guide for evaluation of the efficacy of a given treatment intervention (whether pharmacologic or nonpharmacologic). Documentation will prevent inappropriate concern regarding regulatory issues This portion of the presentation will focus on the management of physical aggression, agitation, and delusions because they are so prevalent in dementia

17 Pharmacotherapy Medications for treating target symptoms
Anticonvulsants Antidepressants Beta-blockers Benzodiazepines Trazodone, buspirone Acetylcholinesterase inhibitors Antipsychotics Memantine Pharmacotherapy Medications for treating target symptoms Medications used in the management of agitation include a broad spectrum of pharmacologic agents, including anticonvulsants, antidepressants, benzodiazepines, beta-blockers, acetylcholin-esterase inhibitors, and antipsychotics. However, it is important to note that there are currently no FDA-approved medications specific for the treatment of agitation and psychosis in dementia The following slides will review the evidence-basis for the current clinical practice of pharmacotherapy for behavioral and psychological symptoms of dementia Kaufer DI, Cummings JL, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer’s disease: an open-label study. J Geriatr Psychiatry Neurol. 1996;9:1-6. Lott AD, McElroy SL, Keys MA. Valproate in the treatment of behavioral agitation in elderly patients with dementia. J Neuropsychiatry Clin Neurosci. 1995;7: Raskind MA, Sadowsky CH, Sigmund WR, et al. Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer’s disease. Arch Neurol. 1997;54: Sultzer DL, Gray KF, Gunay I, et al. A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Am J Geriatr Psychiatry. 1997;5:60-69. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry. 1998;155:54-61.

18 Anticonvulsants Divalproex, carbamazepine
Open trials, case reports, and 4 controlled studies May have specific utility for paroxysmal and aggressive behavior dyscontrol in the absence of psychotic symptoms Anticonvulsants Similar to their increased usage in other areas of psychiatry, anticonvulsant agents such as divalproex and carbamazepine are increasingly utilized for control of agitated behavior in neuropsychiatric conditions such as traumatic brain injury, pervasive developmental disorder (mental retardation syndromes), and dementia-related behavior disturbance. Since many of the studies of these agents have been open-label and uncontrolled, the interpretation of the findings is limited. More well-controlled studies are needed to evaluate their effectiveness Newer anticonvulsants, such as topiramate, lamotrigine, and gabapentin, are currently being studied for the management of behavioral symptoms in the elderly Lott AD, McElroy SL, Keys MA. Valproate in the treatment of behavioral agitation in elderly patients with dementia. J Neuropsychiatry Clin Neurosci. 1995;7: Mellow AM, Solano-Lopez C, Davis S. Sodium valproate in the treatment of behavioral disturbance in dementia. J Geriatr Psychiatry Neurol. 1993;6: Tariot PN, Erb R, Leibovici A, et al. Carbamazepine treatment of agitation in nursing home patients with dementia: a preliminary study. J Am Geriatr Soc. 1994;42: Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry. 1998;155:54-61. Tariot PN, Jakimovich LJ, Erb R et al. Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia. J Clin Psychiatry Oct;60: Sources: Chambers et al. IRCS Med Sci. 1982;10: /Lott AD et al. J Neuropsychiatry Clin Neurosci. 1995;7: /Mellow et al. J Geriatr Psychiatry Neurol. 1993;6: /Tariot PN et al. J Am Geriatr Soc. 1994;42: /Tariot et al. Am J Psychiatry. 1998;155:54-61./Tariot et al. J Clin Psychiatry 1999;60:684-9.

19 Divalproex: Dementia-Related Agitation
Efficacy data emerging Gastrointestinal intolerance and excessive sedation may limit utility* Hepatotoxicity and thrombocytopenia are rare but serious potential side effects Divalproex Dementia-Related Agitation Several small uncontrolled studies suggest that divalproex may be beneficial in some patients with dementia-related agitation Due to side effects, the use of divalproex should be carefully monitored. Excessive sedation and gastrointestinal side effects (eg, nausea, dyspepsia) may limit the utility of divalproex. According to the manufacturer (C. Spath, RPh, oral communication, January 2000), a placebo-controlled trial of divalproex for the treatment of behavioral disturbances in the elderly was recently halted due to excessive somnolence and weight loss in the divalproex group. As a result, a lower dose and slower titration schedule will be utilized in future trials Gastrointestinal side effects can be minimized by the use of the divalproex form of valproic acid and by dosing with food. The use of a low initial starting dose of 62.5 to 125 mg (at bedtime only for at least the first week) may minimize the potential for sedation Although the risk of hepatotoxicity in adults is low, there is a potential for thrombocytopenia. Therefore, baseline lab tests should include complete blood count (CBC) with platelets and transaminases. Periodic monitoring of CBC and liver function should also be conducted during extended treatment with divalproex *A placebo-controlled trial of divalproex for the treatment of behavioral disturbances in the elderly was recently halted due to excessive somnolence and weight loss in the divalproex group (C. Spath, RPh, oral communication, January 2000). As a result, a lower dose and more conservative titration schedule will be utilized in future trials. Source: Lott et al. J Neuropsychiatry Clin Neurosci. 1995;7: /Mellow et al. J Geriatr Psychiatry Neurol. 1993;6:

20 Benzodiazepines Minimal efficacy data Sedating Cause falls
Further inhibit learning and memory Paradoxical disinhibition Commonly used lorazepam oxazepam Benzodiazepines Benzodiazepines are widely used in the elderly, although data supporting their use for the management of agitation and psychosis in this population are very limited, and side effects are of great concern Benzodiazepine use in older adults carries the risk of further cognitive impairment, sedation, falls, and paradoxical behavioral disinhibition Benzodiazepines should be used only if absolutely necessary, at the lowest effective dose, and for a short period of time, until the primary pharmacotherapy (antipsychotic or other agent) begins to work. Short-acting agents (lorazepam, oxazepam) are preferred Other Agents Zolpidem, a nonbenzodiazepine hypnotic, has been studied in elderly patients with insomnia. One study of 14 elderly psychiatric patients with severe insomnia found that use of zolpidem improved total sleep time, sleep efficiency, and percentage of rapid eye movement sleep. There have also been anecdotal reports that zolpidem may be useful for dementia-related insomnia and nighttime wandering, although confirmation of these findings with controlled clinical trials is lacking Source: Coccaro. Am J Psychiatry. 1990;147:

21 Acetylcholinesterase Inhibitors
Drugs used to treat Alzheimer’s disease act by inhibiting acetylcholinesterase activity These drugs block the esterase-mediated metabolism of acetylcholine to choline and acetate. This results in: Increased acetylcholine in the synaptic cleft Increased availability of acetylcholine for postsynaptic and presynaptic nicotinic (and muscarinic) acetylcholine receptors Nordberg A, Svensson A-L. Drug Safety. 1998;19:

22 Memantine in AD FDA approved for moderate-to-severe AD
Studies show slowing of cognitive decline, stabilization or improvement over baseline for >6 months Slowing of decline in functional outcomes Some behavioral symptom reduction (especially apathy, anxious/depressive features)

23 Antipsychotic Drug Prescriptions
AntipsychoticPrescriptions for the Elderly Elderly 13% 24% Other Antipsychotic Drug Prescriptions Although the elderly account for about 13% of the population in the United States, 24% of antipsychotic drug prescriptions are written for elderly patients. It is important for the clinician to ensure appropriate use of these medications in order to produce safe and efficacious clinical outcomes The Omnibus Budget Reconciliation Act (OBRA) regulations were developed in response to a perception of overuse of these medications in long-term care facilities. The OBRA regulations provide guidelines that can be followed in prescribing antipsychotic drugs. Although perceived as placing restrictions on the use of these medications, the OBRA regulations provide a framework for planning appropriate treatment A thoughtful approach to treatment that provides for suitable psychotropic drug intervention as part of an interdisciplinary treatment plan helps to ensure that patients receive antipsychotic medications when appropriate IMS Health, National Disease and Therapeutic Index Audit, Plymouth Meeting, Pennsylvania. August 1999. United States Population Total Prescriptions Source: IMS Health, NDTI. Plymouth Meeting, Pennsylvania. August 1999.

24 Conventional Antipsychotics
Extensive clinical experience Modest efficacy Side effects can hinder treatment High risk of tardive dyskinesia Commonly used in geriatrics Haloperidol Thioridazine Conventional Antipsychotics Although virtually all classes of psychotropic agents have been used to treat agitation in dementia, the mainstay of therapy historically has been the conventional antipsychotic agents Conventional antipsychotics include dopamine–receptor blocking agents such as thioridazine and chlorpromazine, low potency conventional agents, and haloperidol, a high potency conventional agent. All have shown rather modest clinical efficacy Side effects have made their use less desirable, and this is one reason why atypical antipsychotics are supplanting the use of the older drugs Schneider LS, Pollock VE, Lyness SA. A meta analysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc. 1990;38: Tune LE, Steele C, Cooper T. Neuroleptic drugs in the management of behavioral symptoms of Alzheimer’s disease. In: Davidison M, ed. Psychiatric Clinics of North America. Philadelphia, Penn: WB Saunders Co. 1991: Source: Tune et al. In: Davidson M, ed. Psychiatric Clinics of North America. Philadelphia, Penn: WB Saunders Co. 1991:

25 Conventional Antipsychotics: Side Effects Are Predictable
Extrapyramidal symptoms Anticholinergic effects Cognitive toxicity Sedation Orthostatic hypotension Tardive dyskinesia Conventional Antipsychotics Side Effects Are Predictable The side effects of the conventional antipsychotic drugs are predictable, given a basic understanding of their receptor binding profiles The high potency agents (eg, haloperidol) predictably cause a high rate of extrapyramidal side effects (EPS) (eg, iatrogenic parkinsonism) due to their dopamine receptor affinity The low potency agents (eg, thioridazine, chlorpromazine) block 1-adrenergic receptors in smooth muscle cells in the vasculature, causing orthostatic hypotension; block CNS histamine receptors, causing sedation; block peripheral cholinergic receptors, causing tachycardia, blurred vision, constipation/ileus, and urinary retention; and block CNS cholinergic receptors, causing confusion and delirium This wide range of side effects makes conventional antipsychotics difficult to tolerate (engendering noncompliance and poor clinical outcome) in patients of all ages. However, these predictable side effects can be particularly toxic in older patients. Hence, the combination of minimal efficacy and poor tolerability explains the burgeoning interest in the atypical antipsychotic agents Source: Tune et al. In Davidson M, ed. Psychiatric Clinics of North America. Philadelphia, Penn: WB Saunders Co. 1991:

26 Atypical Antipsychotics
Clozapine Olanzapine Quetiapine Risperidone Ziprasidone Aripiprazole Atypical Antipsychotics Four agents are currently available in this class: clozapine, olanzapine, quetiapine, and risperidone. Others are in development The atypical agents, which are a recent addition to the antipsychotic drug armamentarium, differ from the conventional antipsychotics in several important ways. Conventional antipsychotic agents include drugs that have been available since the 1950s (eg, chlorpromazine, the prototype of the low-potency antipsychotics, and haloperidol, the prototype of the high-potency conventional antipsychotics). These agents are presumed to exert their antipsychotic effects (and their significant extrapyramidal side effects) through blockade of CNS dopamine receptors The atypical antipsychotic drugs block a subset of serotonin receptors, in addition to dopamine receptors, which may be the reason for their superior efficacy and safety

27 Risperidone In Dementia-Related Psychosis And Agitation
• Most studied antipsychotic in the elderly • 3 pivotal placebo-controlled trials in dementia patients (N = 1306) • Side-effects equivalent to placebo in therapeutic dose range • Recommended dosing regimen in dementia – Starting dose: 0.25 mg to 0.5 mg hs – Target dose range: 0.5 mg to 1.5 mg hs Aronson SM. Mental Disorders in the Elderly: New Therapeutic Aproaches De Deyn PP et al. Neurology Falsetti AE. Am J Health-Syst Pharm Jeste DV et al. J Clin Psychiatry Snowdon J et al. Am J Geriatr Psychiatry 2002.

28 Risperidone In Dementia
625 Patients With Dementia • Prospective, 12-week, multicenter, placebo-controlled • Randomized to (12 weeks) – Risperidone fixed dose (0.5 mg/d, 1 mg/d, 2 mg/d) – Placebo • Mean age 83 ± 8y; 68% female • Mean MMSE 6.6/30 Katz IR et al. J Clin Psychiatry 1999.

29 Risperidone In Dementia: Results
• 1 mg and 2 mg doses efficacious on outcome measures (BEHAVE-AD, CMAI) • 2 mg dose resulted in higher rate of EPS • 1 mg dose side effect rate equivalent to placebo Katz IR et al. J Clin Psychiatry 1999.

30 LATE-LIFE DEPRESSION Four Hallmarks: Depressed mood Anhedonia
Physical symptoms Psychological symptoms 8

31 DEPRESSED MOOD Hallmark 1
Neither necessary, nor sufficient Can be misleading Beware of asking the question, “Are you depressed?” 9

32 ANHEDONIA Hallmark 2 Loss of interest or pleasure
May be most important and useful hallmark Ask, “What do you enjoy doing?” 10

Sleep disturbance Appetite or weight change Low energy or fatigue Psychomotor changes 11

Low self-esteem or guilt Poor concentration Suicidal ideation or persistent thoughts of death 12

35 MANAGEMENT Support Psychotherapy Psychopharmacology
Electroconvulsive therapy

36 NON-SPECIFIC SUPPORT Reflective listening
If I understand you correctly, you… Empathic communication I can see you feel very sad…(reflection) I can understand…(legitimation) Specific offer of support I am here to help you… Partnership Let’s you and I together… Respect I am very impressed by…

37 PSYCHOTHERAPIES Cognitive-behavioral therapy
Negative thinking, expectations of self and world Interpersonal psychotherapy Role change Problem-solving therapy (pleasant activities) Life narrative review Integrity vs. despair Grief counseling

38 PSYCHOTHERAPY Mild to moderate major depression
Effective Mild to moderate major depression Adjunct to antidepressants Chronic depression Possibly effective Minor depression For patients in life transitions or with personal conflicts Depression in long-term care Depression in AD 40

39 PHARMACOTHERAPY Effective Inconclusive evidence to date
Major depression Chronic depression (dysthymia) Inconclusive evidence to date Minor depression Depression of AD (7 RCT) Lyketsos, Am J Psych 2000 28

40 TREATMENT GUIDELINES Titrate agent to achieve
therapeutic dose or remission Full effect may take 4-6 weeks Continue for 4-9 months after full remission Use maintenance medication for recurrent depressions 29

41 ANTIDEPRESSANTS SSRIs citalopram (Celexa) fluoxetine (Prozac)
TRICYCLICS SSRIs citalopram (Celexa) fluoxetine (Prozac) paroxetine (Paxil) sertraline (Zoloft) OTHER NEW AGENTS bupropion (Wellbutrin) - DA/NE mirtazapine (Remeron) - NE/5HT nefazodone (Serzone) SRI/5HT venlafaxine (Effexor) SRI/NRI 32

Fewer side effects Safety profile Increased patient satisfaction Improved adherence to therapy Cost savings 34

Evaluate: half-life drug interactions side effects 35

44 HALF-LIFE fluoxetine (Prozac) other SSRIs (once a day)
Long (longer than 1 day) fluoxetine (Prozac) Short other SSRIs (once a day) Effexor XR (once a day) Wellbutrin SR (1-2x/day) other new agents (2x/day) 36

45 DRUG INTERACTIONS Obtain medication history
Be aware that all drugs can affect the action and serum levels of other drugs Monitor the clinical effects and serum levels of all medications 36

46 SIDE EFFECTS (SSRIs) Sexual dysfunction Agitation/insomnia GI distress

47 MANAGING SIDE EFFECTS Sedation GI distress Give medication HS
Give medication after meals Anticholinergic effects Bulk in diet, lemon drops Postural hypotension Hydration, change position slowly, support hose

48 Illicit Drug or Alcohol Dependence or Abuse, by Age: 2003
Percent Dependent or Abusing in Past Year Age 50+ 12-13 14-15 16-17 18-20 21-25 26-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65+ Age in Years

49 Alcohol and Illicit Drug Dependence or Abuse, as a Percentage of Total Substance Dependence or Abuse, by Age: 2003 Percent of Substance Dependence/Abuse Alcohol Only Illicit Drug Age 12 to 25 Age 26 to 49 Age 50+

50 Alcohol and Drug Treatment Admissions: Age 50+, 1992-2002
Admissions in Thousands Alcohol Only Drugs

51 Key Themes in Late-Life Alcohol Addiction
Significant underdiagnosis Ageism, shame, misperceptions Increased vulnerability to negative effects of ETOH Increased sensitivity and tolerance

52 Comorbidities Increased risk of hypertension, arrhythmia, mi, cardiomyopathy Hemorrhagic Stroke Cirrhosis GI bleeding Decreased bone density Malnutrition Depression, anxiety

53 Risk Factors Gender Marital Status Bereavement and other losses
Lessening of Role Responsibilities Family history Health care settings Depression

54 Adverse Effects of Late-life Drinking
Decreased quality of life Family burden Medication interactions Trauma Increased suicide risk (10.6 fold increase with 1-2 drinks/day) Adverse medical outcomes

55 Effective Treatment Strategies
Prevention/education Brief advice Brief interventions Referral management Specialized treatments

56 Examples of treatments
Telephone disease management (TDM) Cognitive Behavioral Therapy (CBT) Twelve step programs Motivational interviewing Family involvement/social support

57 Examples of treatments (cont)
Specialty addiction services Pharmacotherapy: Naltrexone Acamprosate Antabuse Others (SSRI’s, topiramate, ondansetron)

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