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psychosis, agitation & difficult behavior in the elderly

Classification: 1) psychosis in the elderly: a) schizophrenia - late onset schizophrenia - early onset in now older patient b) delusional disorder - persecutory vs misidentification delusions - delusions vs hallucinations c) mood disorder with psychosis d) dementia or delirium, with psychosis - psychosis in Alzheimer's disease - Lewy body dementia e) glucocorticoids (steroid psychosis) 2) agitation in the elderly a) risk factors - dementia - psychotic disorders - mood disorders - depression - mania - adjustment disorders - substance abuse disorders b) precipiting factors - delirium - stress - anger - anxiety - frustration - discomfort (see etiology) [44] 3) other behavioral disturbances a) aggressive behavior b) difficult or socially inappropriate behavior c) disruptive behavior Etiology: 1) medications (see drugs commonly producing delirium) - steroid psychosis severe in 6%, mild-moderate in 28% [80] 2) common medical conditions a) delirium & dementia b) dehydration c) infection d) urinary retention e) constipation, fecal impactation f) hypoxia g) depression 3) pain or physical discomfort 4) adjustment to change; misinterpretation of environmental cues 5) intrusion into the patient's personal space 6) poor communication 7) feelings of poor self-esteem due to increasing dependence 8) feelings of insecurity 9) changes in routine, environment, or personnel 10) agitation due to discomfort [44] - being sleepy or tired (62%) - sitting in the same place without movement for > 2 hours (50%) - physical restraints on (29%) - insufficient light (27%) - moving in the seat (26%) - feeling cold (> 10%) - furniture in the way (> 10%) - hunger or thirst in (4%) - other residents bothering the patient (2.8%) - constipation (1%) [44] 11) common in patients with Alzhiemer's disease, but may emerge in patients with mild cognitive impairment or even earlier [78] 12) in patients with moderate to severe dementia greater activity predicted greater behavioral disturbance assessed with NPI-NH score [90] Epidemiology: - 40% of nursing home residents exhibit behavioral disturbances [5] - variation in prescribing patterns in nursing homes [37,39] - ~1/3 of elderly in nursing homes prescribed antipsychotic [38] Pathology: - relevant factors a) lobar atrophy b) regional histopathology - neurofibrillary tangle burden & kalirin-mediated synaptic dysfunction may be neuropathological components of psychosis in Alzheimer's disease [78] c) regional neurochemistry d) regional cortical dysfunction Genetics: - both schizophrenia & Alzheimer's disease risk genes might be involved in psychosis in the elderly Clinical manifestations: 1) relevant factors a) diagnosis b) personal & family history c) see pathology 2) delusions a) prevalence 30-40% in Alzheimer's disease b) themes: persecution, misidentification c) transient d) associated with advanced dementia, agitation, rapid decline 3) agitation a) prevalence 30-50% in Alzheimer's disease b) associated with advanced dementia, premorbid aggression, rapid decline 4) physical aggression: a) prevalence 10-30% in Alzheimer's disease b) associated with advanced dementia, agitation, rapid decline 5) psychosis including hallucinations, paranoia 6) anger 7) mania, emotional lability, disinhibition * see Cohen-Mansfield Agitation Inventory (CMAI) Laboratory: 1) complete blood count 2) basic metabolic panel 3) urinalysis to rule out urinary tract infection Radiology: 1) chest X-ray to rule out cause for delirium if respiratory symptoms 2) PET scan with 2-fluorodeoxyglucose (NOT routine) - may show regional metabolic dysfunction Complications: 1) patient distress, abuse, diminished quality of life 2) caregiver burden, depression, medication use 3) institutionalization & health services use 4) psychosis & agitation rather than its treatment with antipsychotics is associated with institutionalization & death [27] 5) significant cost burden [72] Management: === specific therapies for specific etiologies === - urgent evaluation & management of delirium indicated [92] - discontinue offending medications, especially anticholinergics - encourage use of eye glasses & hearing aids - offer food & water - identify & treat urinary retention & constipation - identify & treat infection - identify & treat pain or discomfort* [86] - if refusal to eat, dental examination [92] - individualized management of delirium precipitants & supportive strategies result in shorter duration of distressing delirium symptoms in palliative care patients than when risperidone or haloperidol is administered [58]. * demented patients may not be able to tell you they are in pain * look for signs of pain & behaviors that may be attributable to pain [86] === behavioral & general measures are 1st line (also see OBRA) === 1) ensure safety [34,79] 2) minimize distress 3) minimize disruption to other patients 4) identify target symptoms & desired outcome 5) behavioral interventions a) repetition b) redirection c) reassurance d) address aggressive behavior 6) environmental modification a) stimulation (overstimulation vs understimulation) [59] b) wandering paths c) visual barriers d) music - personalized music playlists may decrease evening agitation (sundowning) [73] 7) doll therapy [76] 8) structured daily routine 9) caregiver interventions a) education - reasoning will not change the patient's behavior - the caregiver or the environment must change b) mental health assessment & treatment c) respite care d) support groups 10) social interactions & staff training reduce agitation in nursing home patients with dementia [65] 11) multidisciplinary care, massage & touch therapy, & music with massage/touch therapy all clinically effective [69,79] 12) Cochrane review concludes available evidence does not allow for clear generalisable recommendations to reduce antipsychotic use [89] - complex psychosocial interventions may reduce antipsychotic use - medication reconciliation may have some effect of antipsychotic use [89] 13) cognitive behavioral social skills training improves functional skills & social functioning, but not physical function (GRS11) [32] 14) individualized health promotion including fitness & nutrition components may improve physical health [32] 15) see DICE === pharmaceutical agents === 1) treat for pain - severely demented patients: start acetaminophen empirically - acetaminophen likely treats caregiver more than patient - if pain is confirmed, progress the pain ladder to oral morphine as needed 2) neuroleptics (antipsychotics) a) superior to placebo, but efficacy modest b) no clear difference in efficacy among agents c) some patients don't improve; some worsen d) treatment principles 1] use high-potency agents 2] dose conservative, yet sufficient - haloperidol 0.5 mg PO QD prn (max twice weekly) 3] monitor, adjust, consider discontinuation [52] 4] OBRA regulations require documentation of symptoms & attempts to gradually reduce dose 5] discontinuation of antipsychotics after 16 weeks may result in a deterioration of behavior [24] - auditory hallicinations & irritability/lability predict relapse [57] 6] many patients unable to tolerate antipsychotics e) avoid using high-affinity dopamine receptor antagonists (haloperidol, risperidone ..) in patients with Parkinson's disease or Lewy body dementia [42] 1] may worsen cognition 2] may result in neuroleptic malignant syndrome 3] quetiapine preferred agent for patients with Parkinson's disease or Lewy body dementia [32,42] f) atypical antipsychotics [2] effective [46] 1] risperidone, olanzapine, quetiapine (Seroquel), brexpiprazole - brexpiprazole (Rexulti) 1st FDA-approved drug for agitation in patients with Alzheimer's dementia [85] - brexpiprazole (Rxulti) improves agitation in Alzheimer's disease vs placebo over 12 weeks [91] - brexpiprazole & risperidone reduce agitation & aggression in patients with dementia [93] - risperidone probably best option [87] 2] risperidone, olanzapine no better than haloperidol & no less likely to cause adverse effects [4] 3] small increased risk of death within 7 days of initiating haloperidol compared with initiating an atypical antipsychotic in hospitalized elderly after myocardial infarction [67] - survival probability was 0.93 for haloperidol & 0.94 for atypical antipsychotic at day 7 [67] 4] neither quetiapine nor rivastigmine helps with agitation in severely demented patients [8] 5] quetiapine worsens cognition in severely demented patients [8] - GRS9 suggests quetiapine preferred agent in general [32] 6] short term use of atypical antipsychotics associated with 3-5 fold risk of adverse event leading to hospitalization or death [17] 7] somewhat more effective than, but also more toxic than placebo [10] 8] aripiprazole may provide the best balance between efficacy & safety in patients with Alzheimer's disease-associated psychosis [78] f) conventional antipsychotics - haloperidol, start 0.5 mg PO PRN - works as well as atypical antipsychotics - risk of QT prolongation low among antipsychotics [25] g) increased risk of stroke in patients receiving any antipsychotic [20] - RR = 2.3 atypical antipsychotics h) use of antipsychotics (all types) associated with increased mortality in the elderly [5,13,15,21]* 1] 1-year survival vs placebo: 70% vs 77% 2] 2-year survival vs placebo: 46% vs 71% 3] 3-year survival vs placebo: 30% vs 59% [21] 4] risk of mortality may be least with risperidone [13] 5] increased risk of cerebrovascular events [46] i) atypical antipsychotics associated with increased mortality in the elderly: RR = 1.54% [32]; NNH = 50-100 j) increased risk for aspiration pneumonia in patients hospitalized for non-psychiatric conditions (RR=1.5) [63] k) attempt to reduce antipsychotic use should be accompanied by non-pharmacologic measures (i.e. increased social interactions) otherwise neuropsychiatric deterioration may occur [48] l) Cochrane review 1] typical antipsychotics (haloperidol, thiothixene) - uncertain if improve agitation - slightly improve psychosis (low quality evidence) - probably increase somnolence - increase extrapyramidal symptoms - risk of death may be slightly increased 2] atypical antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) - probably reduce agitation - probably negligible effect on psychosis (moderate certainty evidence) - high risk of somnolence - slightly increased risk of extrapyramidal symptoms - risk of death may be slightly increased 3) antidepressants a) SSRI, SNRI - citalopram 30 mg/day reduces agitation & caregiver distress at the cost of greater cognitive decline & increase in QT interval [29] - citalopram benefits some patients, harms others, but most are unaffected [50] - GRS11 asserts citalopram <= 20 mg/day 1st line pharmacologic intervention [32] - sertraline 25-100 mg QD may reduce libido if aggressive sexual behavior b) buspirone c) useful for treatment of anxiety disorder exacerbating dementia-related agitation [64] d) mirtazapine (Remeron) no better than placebo [74] e) clomipramine 25-100 mg QD may reduce obsessive behavior f) avoid using in lieu of antipsychotics in patients with dementia due to potential of falls [79] 4) benzodiazepines - not recommended (MKSAP19) [46] - likely to exacerbate confusion & worsen psychosis & agitation in the elderly [31] - exception is patients with comorbid anxiety disorder [64] - patients at the end-of-life & terminal cancer patients - coadministration with antipsychotic (haloperidol) may be of benefit [46] 5) anticonvulsants a) carbamazepine 1] 200-600 mg/day 2] serum level of 4-8 ug/mL 3] 3 controlled trials, 77% responders b) valproate 1] 250-1500 mg/day 2] serum level of 30-100 ug/mL 3] 11 uncontrolled studies 4] not effective [22,40]; use results in cognitive decline [32] c) valproate or lamotrigine for mania d) gabapentin (Neurontin) e) avoid using in lieu of antipsychotics in patients with dementia due to potential of falls [79] 6) cholinesterase inhibitors a) donepezil, rivastigmine, galantamine b) combination of memantine + donepezil c) donepezil no more effective than placebo [14,16] d) in the absence of alternative safe & effective management options, cholinesterase inhibitors may be an appropriate pharmacological strategy [31] - ref [32] suggests donepezil preferable to haloperidol e) cholinesterase inhibitor therapy significantly ameliorates delusions & hallucinations in patients with Alzheimer disease & Parkinson disease [88] - effect size small (0.08-0.14) [88] f) any improvement in symptoms may take weeks to months [32] 7) quinidine (Nuedexta) may be of benefit [45] 8) bupropion/dextromethorphan (Auvelity) may be of benefit [94] 9) cannabinoids may be of benefit - nabilone may improve symptoms of agitation & aggression among patients with Alzheimer's disease [68] - dronabinol may be useful, especially in combination with cannabidiol [71] 10) propranolol 11) pimavanserin (Nuplazid) induces & maintains remission of dementia-related psychosis; continuation of pimavanserin reduces risk of relapse [70] === new directions === 1) heterogeneity: clinical symptoms & neurobiology 2) pathophysiology of psychiatric & behavioral symptoms 3) validity of symptom clusters 4) specificity of response to treatment 5) integrating treatment of cognitive & behavioral symptoms * see atypical vs conventional antipsychotics in the elderly Notes: - CMS National partnership to improve dementia care inlong-term care (2009-2014) resulted in a decrease in antipsychotic use, but an increase in anticonvulsant use in nursing homes [66]

Interactions

disease interactions

Related

aggressive behavior in the elderly atypical vs conventional antipsychotics in the elderly Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) Cohen-Mansfield Agitation Inventory (CMAI) delirium (acute confusional state) drugs commonly producing delirium elderly (senior citizen) neuropsychiatric features of aging Omnibus Budget Reconciliation Act (OBRA) psychosis in Alzheimer's disease sundowning

General

conduct disorder agitation psychosis geriatric disorder; disease of old age; geriatric syndrome

References

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