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

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Presentation on theme: "Dementia and Psych Meds Andrew S. Rosenzweig, MD, MPH Medical Director, MedOptions Assistant Clinical Professor, Brown University."— Presentation transcript:

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. 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 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 At age 85+, there are 241 women for every 100 men Mental disorders in older adults are under-reported Mental disorders in older adults are under-reported The rate of suicide is highest among older adults compared to any other age group The rate of suicide is highest among older adults compared to any other age group

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

5 Alzheimers Disease (AD): More Than Just Memory Loss AD is a progressive, degenerative disease involving: 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

6 A Peculiar Disease of the Cerebral Cortex Alzheimers Original Case Report (1907) The first case report of Alzheimers 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 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 She screams that her doctor wants to cut her open; at times, she seems to have auditory hallucinations Source: Alzheimer A. Allegmeine Zeitschrift für Psychiatrie. 1907;64:

7 Behavioral and Psychological Symptoms of Dementia Psychosis Delusions Delusions Paranoia Paranoia Hallucinations HallucinationsAgitation Aggression Aggression Combativeness Combativeness Hyperactivity (including wandering) Hyperactivity (including wandering) Hypervocalization Hypervocalization Disinhibition Disinhibition Source: Finkel et al. Am J Geriatr Psychiatry. 1998;6:

8 Behaviors Reported in Agitation and Aggression Agitation Agitation Physical: pacing, inappropriate robing/disrobing, trying to get to a different place, handling things inappropriately, restlessness, stereotypy 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 Aggression Physical: hitting, kicking, pushing, scratching, tearing, biting, spitting Verbal: threats, accusations, name-calling, obscenities

9 Psychosis and Agitation: What We Know Common in Alzheimers disease and other dementing illnesses Common in Alzheimers disease and other dementing illnesses Major source of caregiver distress Major source of caregiver distress Contribute to Contribute to – Premature institutionalization – Increased cost Sources: Drevets et al. Biol Psychiatry. 1989;25:39-48./EllgringNeurology. 1999:52(suppl 3):S17-S20./Rabins PV. Int Psychogeriatr. 1991;3: Sources: Drevets et al. Biol Psychiatry. 1989;25:39-48./Ellgring. Neurology. 1999:52(suppl 3):S17-S20./Rabins PV. Int Psychogeriatr. 1991;3:

10 Prevalence of Symptoms of Psychosis and Agitation in Dementia Cache County Study of Memory in Aging (CCSMA) First US population study of behavioral disturbances in dementia First US population study of behavioral disturbances in dementia Evaluated the prevalence and severity of mental and behavioral disturbances in the elderly Evaluated the prevalence and severity of mental and behavioral disturbances in the elderly 5092 individuals were screened 5092 individuals were screened Participants with dementia (n=329) were compared to control group without dementia (n=673) Participants with dementia (n=329) were compared to control group without dementia (n=673) Source: Lyketsos CG et al. Am J Psychiatry. 2000;157:

11 Prevalence of Symptoms of Psychosis and Agitation in Dementia Source: Adapted with permission from Lyketsos CG et al. Am J Psychiatry. 2000;157: American Psychiatric Association. 21

12 Sources: Rabins PV. Int Psychogeriatr. 1991;3: /Stoppe et al. Drugs Aging. 1999;14: Causes of Distress to Caregivers Physical violence Physical violence Catastrophic reactions Catastrophic reactions Hitting Hitting Making accusations Making accusations Suspiciousness Suspiciousness Incontinence Incontinence Memory disturbance Memory disturbance Inappropriate sexual behavior Inappropriate sexual behavior Disturbing symptoms

13 Sources: Deutsch et al. Am J Psychiatry. 1991;148: /Drevets. Biol Psychiatry. 1989;25: Delusions in Alzheimers Disease Delusional thought content (eg, paranoia) is common (studies suggest 34% to 50% incidence) Delusional thought content (eg, paranoia) is common (studies suggest 34% to 50% incidence) Common delusions 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

14 Effect of Losses in Dementia Normal Feelings Thoughts Behaviors Normal Feelings Thoughts Behaviors Dementia Feelings Short Circuit 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 Approach in a calm manner Use distraction: food, drink, music Use distraction: food, drink, music Maintain eye contact and comfortable posture Maintain eye contact and comfortable posture Match verbal and non-verbal signals Match verbal and non-verbal signals Identify and state the affect observed in the patient Identify and state the affect observed in the patient Identify what is triggering the behavior Identify what is triggering the behavior Modify the environment Modify the environment

16 Target Symptoms for Treatment Physical aggression Physical aggression Agitation Agitation Delusions/paranoia Delusions/paranoia Hallucinations Hallucinations Sleep/wake cycle changes Sleep/wake cycle changes Depression, withdrawal Depression, withdrawal Eating problems Eating problems Verbal outbursts Verbal outbursts

17 Pharmacotherapy Anticonvulsants Anticonvulsants Antidepressants Antidepressants Beta-blockers Beta-blockers Benzodiazepines Benzodiazepines Medications for treating target symptoms Trazodone, buspirone Trazodone, buspirone Acetylcholinesterase inhibitors Acetylcholinesterase inhibitors Antipsychotics Antipsychotics Memantine Memantine

18 Anticonvulsants Divalproex, carbamazepine Open trials, case reports, and 4 controlled studies Open trials, case reports, and 4 controlled studies May have specific utility for paroxysmal and aggressive behavior dyscontrol in the absence of psychotic symptoms May have specific utility for paroxysmal and aggressive behavior dyscontrol in the absence of psychotic symptoms 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./ 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 Efficacy data emerging Gastrointestinal intolerance and excessive sedation may limit utility* Gastrointestinal intolerance and excessive sedation may limit utility* Hepatotoxicity and thrombocytopenia are rare but serious potential side effects Hepatotoxicity and thrombocytopenia are rare but serious potential side effects Source: Lott et al. J Neuropsychiatry Clin Neurosci. 1995;7: /Mellow et al. J Geriatr Psychiatry Neurol. 1993;6: *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.

20 Benzodiazepines Minimal efficacy data Minimal efficacy data Sedating Sedating Cause falls Cause falls Further inhibit learning and memory Further inhibit learning and memory Paradoxical disinhibition Paradoxical disinhibition Commonly used Commonly used – lorazepam – oxazepam Source: Coccaro. Am J Psychiatry. 1990;147:

21 Acetylcholinesterase Inhibitors Drugs used to treat Alzheimers disease act by inhibiting acetylcholinesterase activity Drugs used to treat Alzheimers disease act by inhibiting acetylcholinesterase activity These drugs block the esterase-mediated metabolism of acetylcholine to choline and acetate. This results in: 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 FDA approved for moderate-to-severe AD Studies show slowing of cognitive decline, stabilization or improvement over baseline for >6 months Studies show slowing of cognitive decline, stabilization or improvement over baseline for >6 months Slowing of decline in functional outcomes Slowing of decline in functional outcomes Some behavioral symptom reduction (especially apathy, anxious/depressive features) Some behavioral symptom reduction (especially apathy, anxious/depressive features)

23 Antipsychotic Drug Prescriptions Source: IMS Health, NDTI. Plymouth Meeting, Pennsylvania. August % Total Prescriptions United States Population United States Population Other Elderly 13% Antipsychotic Prescriptions for the Elderly

24 Conventional Antipsychotics Extensive clinical experience Extensive clinical experience Modest efficacy Modest efficacy Side effects can hinder treatment Side effects can hinder treatment High risk of tardive dyskinesia High risk of tardive dyskinesia Commonly used in geriatrics Commonly used in geriatrics – Haloperidol – Thioridazine 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 Extrapyramidal symptoms Anticholinergic effects Anticholinergic effects Cognitive toxicity Cognitive toxicity Sedation Sedation Orthostatic hypotension Orthostatic hypotension Tardive dyskinesia Tardive dyskinesia Source: Tune et al. In Davidson M, ed. Psychiatric Clinics of North America. Philadelphia, Penn: WB Saunders Co. 1991:

26 Atypical Antipsychotics Clozapine Clozapine Olanzapine Olanzapine Quetiapine Quetiapine Risperidone Risperidone Ziprasidone Ziprasidone Aripiprazole Aripiprazole

27 Most studied antipsychotic in the elderlyMost studied antipsychotic in the elderly 3 pivotal placebo-controlled trials in dementia patients (N = 1306)3 pivotal placebo-controlled trials in dementia patients (N = 1306) Side-effects equivalent to placebo in therapeutic dose rangeSide-effects equivalent to placebo in therapeutic dose range Recommended dosing regimen in dementiaRecommended 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 Risperidone In Dementia-Related Psychosis And Agitation

28 Risperidone In Dementia 625 Patients With Dementia Prospective, 12-week, multicenter, placebo-controlledProspective, 12-week, multicenter, placebo-controlled Randomized to (12 weeks)Randomized to (12 weeks) –Risperidone fixed dose (0.5 mg/d, 1 mg/d, 2 mg/d) –Placebo Mean age 83 ± 8y; 68% femaleMean age 83 ± 8y; 68% female Mean MMSE 6.6/30Mean 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)1 mg and 2 mg doses efficacious on outcome measures (BEHAVE-AD, CMAI) 2 mg dose resulted in higher rate of EPS2 mg dose resulted in higher rate of EPS 1 mg dose side effect rate equivalent to placebo1 mg dose side effect rate equivalent to placebo Katz IR et al. J Clin Psychiatry 1999.

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

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

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

33 PHYSICAL SYMPTOMS Hallmark 3 Sleep disturbance Sleep disturbance Appetite or weight change Appetite or weight change Low energy or fatigue Low energy or fatigue Psychomotor changes Psychomotor changes Sleep disturbance Sleep disturbance Appetite or weight change Appetite or weight change Low energy or fatigue Low energy or fatigue Psychomotor changes Psychomotor changes

34 PSYCHOLOGICAL SYMPTOMS Hallmark 4 Low self-esteem or guilt Low self-esteem or guilt Poor concentration Poor concentration Suicidal ideation or persistent Suicidal ideation or persistent thoughts of death thoughts of death Low self-esteem or guilt Low self-esteem or guilt Poor concentration Poor concentration Suicidal ideation or persistent Suicidal ideation or persistent thoughts of death thoughts of death

35 MANAGEMENTMANAGEMENT Support Support Psychotherapy Psychotherapy Psychopharmacology Psychopharmacology Electroconvulsive therapy Electroconvulsive therapy

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

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

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

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

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

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

42 ADVANTAGES OF SSRIs AND OTHER NEW AGENTS Fewer side effects Fewer side effects Safety profile Safety profile Increased patient satisfaction Increased patient satisfaction Improved adherence to therapy Improved adherence to therapy Cost savings Cost savings Fewer side effects Fewer side effects Safety profile Safety profile Increased patient satisfaction Increased patient satisfaction Improved adherence to therapy Improved adherence to therapy Cost savings Cost savings

43 CHOOSING AMONG SSRIs AND OTHER NEW AGENTS Evaluate: Evaluate: half-life half-life drug interactions drug interactions side effects side effects Evaluate: Evaluate: half-life half-life drug interactions drug interactions side effects side effects

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

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

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

47 MANAGING SIDE EFFECTS Sedation Sedation –Give medication HS GI distress GI distress –Give medication after meals Anticholinergic effects Anticholinergic effects –Bulk in diet, lemon drops Postural hypotension 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 in Years Age 50+

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

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

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

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

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

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

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

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

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


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