Скачать презентацию 失智症常見精神行為症狀與治 療 財團法人奇美醫院柳營院區精 神科 許森彥醫師 2007年 10月 20日 Скачать презентацию 失智症常見精神行為症狀與治 療 財團法人奇美醫院柳營院區精 神科 許森彥醫師 2007年 10月 20日

934e2c5f51dc3dcd67cb0a922d69737a.ppt

  • Количество слайдов: 46

失智症常見精神行為症狀與治 療 財團法人奇美醫院柳營院區精 神科 許森彥醫師 2007年 10月 20日 失智症常見精神行為症狀與治 療 財團法人奇美醫院柳營院區精 神科 許森彥醫師 2007年 10月 20日

Psychosis and Agitation Associated with Dementia • Prevalent 10 -80% • Persistent n=235, for Psychosis and Agitation Associated with Dementia • Prevalent 10 -80% • Persistent n=235, for 5 years (Devanand DP, 1997) • Contribute to caregiver suffering review (Connell CM, 2001) • Accelerate functional and cognitive decline n=181, for 1. 5 years (Levy ML, 1996) • Premature institutionalization 25 pairs, for 3 years (Steele C, 1990)

Incidence of and Risk Factors for Hallucinations and Delusions in Patients with Probable AD Incidence of and Risk Factors for Hallucinations and Delusions in Patients with Probable AD • Authors: Paulsen, J S. Salmon, D P. Thal, L J. et al. • Source: Neurology. 54(10): 1965 -71, 2000 May 23. • Methods: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer's Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whethere were specific risk factors for the development of hallucinations and delusions.

Incidence of and Risk Factors RESULTS: 1. The cumulative incidence of hallucinations and delusions Incidence of and Risk Factors RESULTS: 1. The cumulative incidence of hallucinations and delusions was 20. 1% at 1 year, 36. 1% at 2, 49. 5% at 3, and 51. 3% at 4 years. 2. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. 3. Age, education, and gender were not significant predictors.

Mental and Behavioral Disturbances in Dementia: Findings from the Cache County Study on Memory Mental and Behavioral Disturbances in Dementia: Findings from the Cache County Study on Memory in Aging • Authors: Lyketsos, C G. Steinberg, M. Tschanz, J T. et al. • Source: AJP 157(5): 708 -14, 2000 May. • METHOD: The 5, 092 participants, who were 65 years old or older, were screened for dementia. Based on the results of this screen, 1, 002 participants (329 with dementia and 673 without dementia) underwent comprehensive neuropsychiatric examinations and were rated on the Neuropsychiatric Inventory (NPI).

Results of CCSMA Study 1. 214 (65%) had AD, 62 (19%) had VD, and Results of CCSMA Study 1. 214 (65%) had AD, 62 (19%) had VD, and 53 (16%) had another DSM-IV dementia diagnosis. 2. 201 (61%) had exhibited one or more mental or behavioral disturbances in the past month. 3. Apathy (27%), depression (24%), and agitation/aggression (24%) were the most common in participants with dementia. 4. These disturbances were almost four times more common in participants with dementia than in those without. 5. Participants with Alzheimer's disease were more likely to have delusions and less likely to have depression. 6. Agitation/aggression and aberrant motor behavior were more common in participants with advanced dementia.

Further Analysis of CCSMA Data 1. A latent class analysis revealed that these participants Further Analysis of CCSMA Data 1. A latent class analysis revealed that these participants could be classified into three groups (classes) based on their neuropsychiatric symptom profile. 2. The largest class included cases with no neuropsychiatric symptoms (40%) or with a mono-symptomatic disturbance (19%). 3. A second class (28%) exhibited a predominantly affective syndrome, 4. Lyketsos CG. Sheppard JM. Steinberg M. et al. International Journal of A third class (13%) had a psychotic syndrome. Geriatric Psychiatry. 16(11): 1043 -53, 2001 Nov.

Subtypes of Psychotic Symptoms in Alzheimer disease 1. Factor and cluster analyses of the Subtypes of Psychotic Symptoms in Alzheimer disease 1. Factor and cluster analyses of the psychoticsymptom items of the CERAD Behavioral Rating Scale in 188 probable and possible AD subjects who have displayed at least one psychotic symptom. 2. Exploratory factor analysis resulted in a onefactor solution that comprised misidentification delusions, auditory and visual hallucinations, and the misidentification of people. 3. Persecutory delusions were also frequently present and were independent of the misidentification/hallucination factor. Cook SE. Miyahara S. Bacanu SA. et al. American Journal of Geriatric Psychiatry. 11(4): 406 -13, 2003 Jul-Aug.

The Relationship between Psychiatric Symptoms and Regional Cortical Metabolism in Alzheimer's Disease 1. Agitation/ The Relationship between Psychiatric Symptoms and Regional Cortical Metabolism in Alzheimer's Disease 1. Agitation/ Disinhibition factor score and metabolism in the frontal and temporal lobes 2. Psychosis factor score and metabolism in the frontal lobe 3. Anxiety/Depression factor score and metabolism in the parietal lobe. Sultzer DL. Mahler ME. Mandelkern MA. et al. Journal of Neuropsychiatry & Clinical Neurosciences. 7(4): 476 -84, 1995.

Delusions in AD • Definition: A fixed false beliefs that are not attributable to Delusions in AD • Definition: A fixed false beliefs that are not attributable to membership in a social or cultural group. • A review of 35 studies revealed the prevalence between 16 to 70 % (median 36. 5 %)1 • The CCSMA study reported an incidence of delusions of 28% within 18 months. 2 1. Bassiony MM. Lyketsos CG. Psychosomatics. 44(5): 388 -401, 2003 Sep-Oct. 2. Steinberg M. Sheppard JM. Tschanz JT. et al. Journal of Neuropsychiatry & Clinical Neurosciences. 15(3): 340 -5, 2003.

Delusions in AD • Delusion of stealing is the most prevalent, followed by persecutory Delusions in AD • Delusion of stealing is the most prevalent, followed by persecutory delusions, delusion of reference, infidelity, grandiosity, and somatic delusions. 1 • The presence of delusions in AD was associated with greater cognitive impairment, especially frontal/temporal dysfunction, and possibly with a more rapidly progressive dementia. 2 1. Bassiony MM. Lyketsos CG. Psychosomatics. 44(5): 388 -401, 2003 Sep. Oct. 2. Jeste DV. Wragg RE. Salmon DP. Harris MJ. Thal LJ. American Journal of Psychiatry. 149(2): 184 -9, 1992 Feb.

Hallucinations in AD • Definition: False sensory perceptions. • A review of 35 studies Hallucinations in AD • Definition: False sensory perceptions. • A review of 35 studies revealed the prevalence between 4 to 76 % (median 23 %)1 • The CCSMA study reported an incidence of hallucinations of 16% within 18 months. 2 1. Bassiony MM. Lyketsos CG. Psychosomatics. 44(5): 388 -401, 2003 Sep-Oct. 2. Steinberg M. Sheppard JM. Tschanz JT. et al. Journal of Neuropsychiatry & Clinical Neurosciences. 15(3): 340 -5, 2003.

Hallucinations in AD • Visual (4 -59 %, median 23 %) and auditory (1 Hallucinations in AD • Visual (4 -59 %, median 23 %) and auditory (1 -29 %, median 12 %) hallucinations are far more prevalent than tactile, olfactory and somatic hallucinations. 1 • The presence of hallucinations may be more common in the later stage of AD. 2 1. Bassiony MM. Lyketsos CG. Psychosomatics. 44(5): 388 -401, 2003 Sep. Oct. 2. Devanand DP. Brockington CD. Moody BJ. et al. International Psychogeriatrics. 4 Suppl 2: 161 -84, 1992. .

 • • Misidentification Phenomenon A prevalence of 23% to 50% has been reported. • • Misidentification Phenomenon A prevalence of 23% to 50% has been reported. 1, 2 Common manifestations: 3 – The failure to recognize one’s home (“this is not my home” phenomenon) – Belief that strangers are living in the house (phantom boarder syndrome) – Belief that loved ones are impostors (Capgras phenomenon) 1. Rubin E, Drevets W, Burke A. J Geriatr Psychiatry Neurol. 1: 16 -20, 1988. 2. Merriam A, Aronson N, Gaston P, et al. J Am Geriatr Soc. 26: 7 -12, 1988. 3. Leroi I. Voulgari A. Breitner JC. Lyketsos CG. American Journal of Geriatric Psychiatry. 11(1): 83 -91, 2003 Jan-Feb.

Agitation of Dementia • Problem behaviors or disruptive behaviors • Definition: – Inappropriate verbal, Agitation of Dementia • Problem behaviors or disruptive behaviors • Definition: – Inappropriate verbal, vocal, or motoric activity that is not judged by an outside observer to result directly from the needs or confusion of the agitated individual. (Cohen-Mansfield J, 1986) – Behaviors that is disruptive, unsafe or interferes with care in a given environment. (Rosen J, 1994)

Behavioral and Psychological Symptoms of Dementia (BPSD) • A heterogeneous range of psychological reactions, Behavioral and Psychological Symptoms of Dementia (BPSD) • A heterogeneous range of psychological reactions, psychiatric symptoms, and behaviors occurring in people with dementia of any etiology. • Defined by International Psychogeriatric Association in 1996.

Classification of Agitated Behaviors • Aggressive behaviors • Physically non-aggressive behaviors • Verbal/vocal agitated Classification of Agitated Behaviors • Aggressive behaviors • Physically non-aggressive behaviors • Verbal/vocal agitated behaviors

Aggressive Behaviors • Hitting, biting, kicking, spitting, pushing, grabbing, scratching, tearing things, hurting self Aggressive Behaviors • Hitting, biting, kicking, spitting, pushing, grabbing, scratching, tearing things, hurting self or others, physical sexual advances • Correlated with male gender, severe cognitive impairment, premorbid aggressive personality, psychosis, feeling of been intruded

Physically Non-aggressive Behaviors • Hiding objects, hoarding objects, general restlessness, intentional falling, pacing, aimless Physically Non-aggressive Behaviors • Hiding objects, hoarding objects, general restlessness, intentional falling, pacing, aimless wandering, trying to get to a difference place, handling things inappropriately, eating inappropriate substances, inappropriate dressing and disrobing, performing repetitious mannerisms • More active throughout their lives and less medical conditions • Akathisia should be considered under antipsychotics exposure.

Verbal/vocal Agitated Behaviors • Most frequently • Repetitive sentences or questions, unwarranted requests for Verbal/vocal Agitated Behaviors • Most frequently • Repetitive sentences or questions, unwarranted requests for attention or help, complaining, negativism, making strange noises, screaming, verbal sexual advances, cursing and verbal aggression • Correlated with female gender, poor health, pain, depression

Management of agitation and psychosis Management of agitation and psychosis

Assessment of Psychosis and Agitation • The ABCs of dementia management 1. Antecedents 2. Assessment of Psychosis and Agitation • The ABCs of dementia management 1. Antecedents 2. Behavior 3. Consequences • The strategy of identifying stimuli – Stimulus-Response

Antecedents • Medical – Urinary tract infection, pain, … • Environmental – Noise, ambient Antecedents • Medical – Urinary tract infection, pain, … • Environmental – Noise, ambient temperature, … • Psychiatric – New onset delusion, … • Social – Recent housing relocation, … • Related to caregiver’s approach

Characterizing Behavioral Disturbance • • • Verbal or physical ? Aggressive or non-aggressive ? Characterizing Behavioral Disturbance • • • Verbal or physical ? Aggressive or non-aggressive ? Frequency ? Severity ? Timing ? Location ? Level of disruptiveness ? Who was/were involved ? The use of psychopathology rating instrument

Consequences • Inadvertent reinforcement – The consequences of the disruptive behaviors itself reinforce its Consequences • Inadvertent reinforcement – The consequences of the disruptive behaviors itself reinforce its propagation.

Internal Stimuli Internal Stimuli

External Stimuli External Stimuli

Treatment of Psychosis and Agitation Associated with Dementia • Non-pharmacological interventions • Pharmacological interventions Treatment of Psychosis and Agitation Associated with Dementia • Non-pharmacological interventions • Pharmacological interventions

Non-pharmacological Interventions • Theoretical considerations: 1. Addressing unmet physical, emotional, and psychological needs 2. Non-pharmacological Interventions • Theoretical considerations: 1. Addressing unmet physical, emotional, and psychological needs 2. Application of behavior modification principles 3. Accommodation of reduced stress tolerance as a result of cognitive and physical decline

Non-pharmacological Interventions • Modalities: 1. 2. 3. 4. 5. 6. 7. 8. Music therapy Non-pharmacological Interventions • Modalities: 1. 2. 3. 4. 5. 6. 7. 8. Music therapy Real or simulated social contact Behavior therapy Staff training Activities Environmental modification Medical/nursing interventions Combined therapies

Pharmacological Interventions • A mean improvement rate of 61%(S. D. 18%) for typical and Pharmacological Interventions • A mean improvement rate of 61%(S. D. 18%) for typical and atypical antipsychotics combined, compared with 35%(S. D. 20%) for placebo. • The improvement rate with atypical antipsychotics appears to be slightly higher 72%(S. D. 24%). Kindermann SS. Dolder CR. Bailey A. Katz IR. Jeste DV. Drugs & Aging. 19(4): 257 -76, 2002.

Atypical Antipsychotics for Agitation Associated with Dementia Medicatio ns Starting Dose (mg/d) Therapeut Main Atypical Antipsychotics for Agitation Associated with Dementia Medicatio ns Starting Dose (mg/d) Therapeut Main Adverse ic Dose Effects (mg/d) Special Precautions Risperido ne 0. 25 -0. 5 1 -2 Sedation, EPS, orthostasis, peripheral edema Active metabolite accumulates with renal failure Olanzapin 2. 5 -5 e 5 -15 Sedation, EPS, orthostasis Metabolic effects, anticholinergic ity Quetiapin e 100 -400 Sedation, orthostasis — 12. 5 -25

Selective Serotonin Re-uptake Inhibitors for Agitation Associated with Dementia Medication Starting s Dose (mg/d) Selective Serotonin Re-uptake Inhibitors for Agitation Associated with Dementia Medication Starting s Dose (mg/d) Therapeutic Main Dose (mg/d) Adverse Effects Special Precautions Sertraline 25 100 -200 Nausea, diarrhea, insomnia Hyponatremia ; EPS Escitalopr am 5 -10 10 -20 Nausea, headache, constipation Hyponatremia ; EPS

Benzodiazepines for Agitation Associated with Dementia Medication Starting s Dose (mg/d) Therapeutic Main Dose Benzodiazepines for Agitation Associated with Dementia Medication Starting s Dose (mg/d) Therapeutic Main Dose (mg/d) Adverse Effects Special Precautions Lorazepam 0. 25 1 -2 Sedation, ataxia, cognitive impairment Avoid chronic use Oxazepam 15 15 -30 Sedation, ataxia, cognitive impairment Avoid chronic use

Anticonvulsants for Agitation Associated with Dementia Medications Starting Dose (mg/d) Therapeuti Main c Dose Anticonvulsants for Agitation Associated with Dementia Medications Starting Dose (mg/d) Therapeuti Main c Dose Adverse (mg/d) Effects Special Precautions Divalproex sodium 125 -250 250 -1000 Nausea, sedation Thrombocytope nia, liver function abnormalities, pancreatitis 200 -1000 Sedation, ataxia, nausea Hyponatremia, pancytopenia Carbamazepi 50 -100 ne

Acetylcholinesterase Inhibitors for Agitation Associated with Dementia Medication s Starting Dose (mg/d) Therapeu Main Acetylcholinesterase Inhibitors for Agitation Associated with Dementia Medication s Starting Dose (mg/d) Therapeu Main Adverse tic Dose Effects (mg/d) Special Precautions Donepezil 5 5 -15 Nausea, diarrhea, transient confusion Bradycardia possible Rivastigmi ne 3 6 -12 Nausea, diarrhea, transient confusion Bradycardia possible 16 -24 Nausea, diarrhea, transient Bradycardia possible Galantamin 8 e

Other agents for Agitation Associated with Dementia Medication s Starting Dose (mg/d) Therapeu Main Other agents for Agitation Associated with Dementia Medication s Starting Dose (mg/d) Therapeu Main Adverse Special tic Dose Effects Precautions (mg/d) Trazodone 50 50 -150 Sedation, orthostasis Priapiam (rare) Arrythmia (at higher doses) Memantine 5 20 Sedation Not recommended for patients with severe renal function impairment

Memantine 1. A moderate-affinity, uncompetitive N-methyl-Daspartate (NMDA) receptor antagonist. 2. Might reduce the need Memantine 1. A moderate-affinity, uncompetitive N-methyl-Daspartate (NMDA) receptor antagonist. 2. Might reduce the need for antipsychotics. 3. The dose recommended is 20 mg/d (10 mg twice a day). 4. Mostly excreted through the kidneys. 5. The most common side effects (≧ 5%) are dizziness, constipation, confusion and headaches, less common side effects (≦ 5%) are hypertension, somnolence and visual Gauthier S. Herrmann hallucinations. N. Ferreri F. Agbokou C. CMAJ. 175(5): 5012, 2006 Aug 29.

Behavioral Effects of Memantine in Alzheimer Disease Patients Receiving Donepezil Treatment. • Cummings JL. Behavioral Effects of Memantine in Alzheimer Disease Patients Receiving Donepezil Treatment. • Cummings JL. Schneider E. Tariot PN. Graham SM. • Memantine MEM-MD-02 Study Group. • Clinical Trial. Comparative Study. Journal Article. Multicenter Study. Randomized Controlled Trial. Research Support, N. I. H. , Extramural. Research Support, Non-U. S. Gov't • Neurology. 67(1): 57 -63, 2006 Jul 11.

N=404, Probable AD MMSE score of 5 to 14 at both screening and baseline N=404, Probable AD MMSE score of 5 to 14 at both screening and baseline At least 50 years of age Receiving ongoing therapy donepezil for at least 6 months and had been on a stable dose (5 or 10 mg/day) for at least 3 months

The results of this post-hoc analysis partially support the hypothesis that memantine would have The results of this post-hoc analysis partially support the hypothesis that memantine would have preferential effects on frontally mediated behavioral disturbances.

Pharmacological Management of Behavioral Emergencies • If PO administration possible: – Risperidone 0. 5 Pharmacological Management of Behavioral Emergencies • If PO administration possible: – Risperidone 0. 5 mg (range 0. 25 -1 mg) or – Olanzapine 5 mg (range 2. 5 -5 mg) or – Quetiapine 25 mg (range 25 -50 mg) • If IM administration necessary: – Olanzapine 5 mg or – Haloperidol 0. 5 mg (range 0. 5 -1 mg); monitor EPS • If IV access available: – Haloperidol 0. 5 mg (range 0. 5 -1 mg); monitor QTc prolongation and/or ventricular arrhythmias at high dose • For severe agitation, augment any of the above preparations with: – Lorazepam 0. 5 -1 mg PO/IM

Ethical Issues • The ability to give informed consent – Explain the side effects Ethical Issues • The ability to give informed consent – Explain the side effects and their possible consequences toward the patients and their care givers in the laymen’s terms – Written documentation of informed consent • Balancing patient needs versus system needs – Individualizing patient care is problematic in inflexible residential environments

Thanks for Your Attention ! Thanks for Your Attention !