psychosis, agitation & difficult behavior in the elderly
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Classification
- psychosis in the elderly:
- schizophrenia
- late onset schizophrenia
- early onset in now older patient
- delusional disorder
- persecutory vs misidentification delusions
- delusions vs hallucinations
- mood disorder with psychosis
- dementia or delirium, with psychosis
- glucocorticoids (steroid psychosis)
- schizophrenia
- agitation in the elderly
- risk factors
- precipiting factors
- other behavioral disturbances
- aggressive behavior
- difficult or socially inappropriate behavior
- disruptive behavior
Etiology
- medications (see drugs commonly producing delirium)
- steroid psychosis severe in 6%, mild-moderate in 28%[80]
- common medical conditions
- pain or physical discomfort
- adjustment to change; misinterpretation of environmental cues
- intrusion into the patient's personal space
- poor communication
- feelings of poor self-esteem due to increasing dependence
- feelings of insecurity
- changes in routine, environment, or personnel
- 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]
- common in patients with Alzhiemer's disease, but may emerge in patients with mild cognitive impairment or even earlier[78]
- 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
- lobar atrophy
- regional histopathology
- neurofibrillary tangle burden & kalirin-mediated synaptic dysfunction may be neuropathological components of psychosis in Alzheimer's disease[78]
- regional neurochemistry
- regional cortical dysfunction
Genetics
- both schizophrenia & Alzheimer's disease risk genes might be involved in psychosis in the elderly
Clinical manifestations
- relevant factors
- diagnosis
- personal & family history
- see pathology
- delusions
- prevalence 30-40% in Alzheimer's disease
- themes: persecution, misidentification
- transient
- associated with advanced dementia, agitation, rapid decline
- agitation
- prevalence 30-50% in Alzheimer's disease
- associated with advanced dementia, premorbid aggression, rapid decline
- physical aggression:
- prevalence 10-30% in Alzheimer's disease
- associated with advanced dementia, agitation, rapid decline
- psychosis including hallucinations, paranoia
- anger
- mania, emotional lability, disinhibition
Laboratory
Radiology
- chest X-ray to rule out cause for delirium if respiratory symptoms
- PET scan with 2-fluorodeoxyglucose (NOT routine)
- may show regional metabolic dysfunction
Complications
- patient distress, abuse, diminished quality of life
- caregiver burden, depression, medication use
- institutionalization & health services use
- psychosis & agitation rather than its treatment with antipsychotics is associated with institutionalization & death[27]
- 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)
- ensure safety[34][79]
- minimize distress
- minimize disruption to other patients
- identify target symptoms & desired outcome
- behavioral interventions
- repetition
- redirection
- reassurance
- address aggressive behavior
- environmental modification
- doll therapy[76]
- structured daily routine
- caregiver interventions
- education
- reasoning will not change the patient's behavior
- the caregiver or the environment must change
- mental health assessment & treatment
- respite care
- support groups
- education
- social interactions & staff training reduce agitation in nursing home patients with dementia[65]
- multidisciplinary care, massage & touch therapy, & music with massage/touch therapy all clinically effective[69][79]
- 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]
- cognitive behavioral social skills training improves functional skills & social functioning, but not physical function (GRS11)[32]
- individualized health promotion including fitness & nutrition components may improve physical health[32]
- see DICE
pharmaceutical agents
- 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
- severely demented patients: start acetaminophen empirically
- neuroleptics (antipsychotics)
- superior to placebo, but efficacy modest
- no clear difference in efficacy among agents
- some patients don't improve; some worsen
- treatment principles
- use high-potency agents
- dose conservative, yet sufficient
- haloperidol 0.5 mg PO QD prn (max twice weekly)
- monitor, adjust, consider discontinuation[52]
- OBRA regulations require documentation of symptoms & attempts to gradually reduce dose
- discontinuation of antipsychotics after 16 weeks may result in a deterioration of behavior[24]
- auditory hallicinations & irritability/lability predict relapse[57]
- many patients unable to tolerate antipsychotics
- avoid using high-affinity dopamine receptor antagonists (haloperidol, risperidone ..) in patients with Parkinson's disease or Lewy body dementia[42]
- may worsen cognition
- may result in neuroleptic malignant syndrome
- quetiapine preferred agent for patients with Parkinson's disease or Lewy body dementia[32][42]
- atypical antipsychotics[2] effective[46]
- risperidone, olanzapine, quetiapine (Seroquel), brexipiprazole
- brexipiprazole (Rexulti) 1st FDA-approved drug for agitation in patients with Alzheimer's dementia[85]
- brexpipraxole (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]
- risperidone, olanzapine no better than haloperidol & no less likely to cause adverse effects[4]
- 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]
- neither quetiapine nor rivastigmine helps with agitation in severely demented patients[8]
- quetiapine worsens cognition in severely demented patients[8]
- GRS9 suggests quetiapine preferred agent in general[32]
- short term use of atypical antipsychotics associated with 3-5 fold risk of adverse event leading to hospitalization or death[17]
- somewhat more effective than, but also more toxic than placebo[10]
- aripiprazole may provide the best balance between efficacy & safety in patients with Alzheimer's disease-associated psychosis[78]
- risperidone, olanzapine, quetiapine (Seroquel), brexipiprazole
- conventional antipsychotics
- haloperidol, start 0.5 mg PO PRN
- works as well as atypical antipsychotics
- risk of QT prolongation low among antipsychotics[25]
- haloperidol, start 0.5 mg PO PRN
- increased risk of stroke in patients receiving any antipsychotic[20]
- RR = 2.3 atypical antipsychotics
- use of antipsychotics (all types) associated with increased mortality in the elderly[5][13][15][21]*
- atypical antipsychotics associated with increased mortality in the elderly: RR = 1.54%[32]; NNH = 50-100
- increased risk for aspiration pneumonia in patients hospitalized for non-psychiatric conditions (RR=1.5)[63]
- attempt to reduce antipsychotic use should be accompanied by non-pharmacologic measures (i.e. increased social interactions) otherwise neuropsychiatric deterioration may occur[48]
- Cochrane review
- 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
- 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
- typical antipsychotics (haloperidol, thiothixene)
- antidepressants
- 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
- buspirone
- useful for treatment of anxiety disorder exacerbating dementia-related agitation[64]
- mirtazapine (Remeron) no better than placebo[74]
- clomipramine 25-100 mg QD may reduce obsessive behavior
- avoid using in lieu of antipsychotics in patients with dementia due to potential of falls[79]
- SSRI, SNRI
- 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]
- anticonvulsants
- carbamazepine
- valproate
- valproate or lamotrigine for mania
- gabapentin (Neurontin)
- avoid using in lieu of antipsychotics in patients with dementia due to potential of falls[79]
- cholinesterase inhibitors
- donepezil, rivastigmine, galantamine
- combination of memantine + donepezil
- donepezil no more effective than placebo[14][16]
- 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
- cholinesterase inhibitor therapy significantly ameliorates delusions & hallucinations in patients with Alzheimer disease & Parkinson disease[88]
- effect size small (0.08-0.14)[88]
- any improvement in symptoms may take weeks to months [32]
- dextromethorphan/quinidine (Nuedexta) may be of benefit[45]
- 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]
- propranolol
- pimavanserin (Nuplazid) induces & maintains remission of dementia-related psychosis; continuation of pimavanserin reduces risk of relapse[70]
new directions
- heterogeneity: clinical symptoms & neurobiology
- pathophysiology of psychiatric & behavioral symptoms
- validity of symptom clusters
- specificity of response to treatment
- 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]
More general terms
Additional terms
- aggressive behavior in the elderly
- atypical vs conventional antipsychotics in the elderly
- Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE)
- 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
References
- ↑ Sultzer, D. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 2.0 2.1 Prescriber's Letter 8(7):40 2001 Doody RS et al, Practice Parameter: management of dementia (an evidence-based review). Report of the quality standards subcommitte of the American Academy of Neurology, Neurology 56:1154-1156, 2001 (Guideline withdrawn 02/2009) PMID: https://www.ncbi.nlm.nih.gov/pubmed/11342679
- ↑ Sultzer, D. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 25-28, 2002
- ↑ 4.0 4.1 Journal Watch 24(17):133, 2004 Lee PE, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ. 2004 Jul 10;329(7457):75. Epub 2004 Jun 11. Review. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15194601 <Internet> http://bmj.bmjjournals.com/cgi/content/full/329/7457/75
- ↑ 5.0 5.1 5.2 Rovner BW, German PS, Broadhead J, Morriss RK, Brant LJ, Blaustein J, Folstein MF. The prevalence and management of dementia and other psychiatric disorders in nursing homes. Int Psychogeriatr. 1990 Spring;2(1):13-24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2101294
- ↑ FDA Public Health Advisory Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances http://www.fda.gov/cder/drug/advisory/antipsychotics.htm http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#atypical
- ↑ Prescriber's Letter 12(6): 2005 Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210604&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 8.2 Journal Watch 25(12):96, 2005
Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. BMJ. 2005 Apr 16;330(7496):874. Epub 2005 Feb 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15722369
Gauthier S Drugs for Alzheimer's disease and related dementias. BMJ. 2005 Apr 16;330(7496):857-8. No abstract available. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15831849 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7496/874 - ↑ Wang PS, Schneeweiss S, Avorn J, Fischer MA, Mogun H, Solomon DH, Brookhart MA. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005 Dec 1;353(22):2335-41. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16319382
Ray WA. Observational studies of drugs and mortality. N Engl J Med. 2005 Dec 1;353(22):2319-21. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16319379 - ↑ 10.0 10.1 Schneider LS Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease N Engl J Med 2006, 355:1525 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17035647
Karlawish J Alzheimer's disease - Clinical trials and the logic of clinical purpose. N Engl J Med 2006, 355:1604 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17035654 - ↑ Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003476. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16437455
- ↑ Cummmins JL et al, for Memantine MEM-MD-02 Study Group Behavioral effects memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006, 67:57 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16832078
- ↑ 13.0 13.1 13.2 Schneeweiss S et al, Risk of death with use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007, 176:627 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17325327
- ↑ 14.0 14.1 Howard RJ et al, Donepezil for the treatment of agitation in Alzheimer's disease. N Engl J Med 2007, 357:1382 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17914039
- ↑ 15.0 15.1 Kales HC, Valenstein M, Kim HM, McCarthy JF, Ganoczy D, Cunningham F, Blow FC. Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications. Am J Psychiatry. 2007 Oct;164(10):1568-76. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17898349
- ↑ 16.0 16.1 Yaffe K. Treatment of neuropsychiatric symptoms in patients with dementia. N Engl J Med 2007, 357:1411 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17914047
- ↑ 17.0 17.1 Rochon PA et al, Antipsychotic Therapy and Short-term Serious Events in Older Adults With Dementia Arch Intern Med 2008 168:1090 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18504337
- ↑ FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antipsychotics
- ↑ Sultzer DL et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: Phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry 2008 Jul; 165:844 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18519523
Kuehn BM. FDA: Antipsychotics risky for elderly. JAMA 2008 Jul 23/30; 300:379 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18647971 - ↑ 20.0 20.1 Douglas IJ and Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008 Aug 28; 337:a1227. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18755769
- ↑ 21.0 21.1 21.2 Ballard C et al The dementia antipsychotic withdrawal trial (DART-AD): Long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 2009 Feb; 8:151. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19138567 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(08)70295-3/fulltext
- ↑ 22.0 22.1 Tariot PN et al. for the Alzheimer's Disease Cooperative Study Group. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry 2011 Aug; 68:853. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21810649
- ↑ Prescriber's Letter 18(10): 2011 CHART: Pharmacotherapy of Dementia Behaviors CHART: Pharmacotherapy of Dementia Behaviors Algorithm GUIDELINES: American Psychiatric Association Dementia Guideline Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271010&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 24.0 24.1 Devanand DP et al Relapse Risk after Discontinuation of Risperidone in Alzheimer's Disease N Engl J Med 2012; 367:1497-1507 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23075176 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1114058
- ↑ 25.0 25.1 Campbell N, Boustani MA, Ayub A, et al. Pharmacological management of delirium in hospitalized adults- a systematic evidence review. J Gen Intern Med 2009; 24:848-853 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19424763
- ↑ Husebo BS, Ballard C, Sandvik R, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ 2011; 343:d4065 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21765198
- ↑ 27.0 27.1 Lopez OL et al. The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer's disease. Am J Psychiatry 2013 Jul 30 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23896958 <Internet> http://ajp.psychiatryonline.org/article.aspx?articleID=1722043
- ↑ Ballard C, Corbett A. Agitation and aggression in people with Alzheimer's disease. Curr Opin Psychiatry. 2013 May;26(3):252-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23528917
Ballard C, Corbett A. Management of neuropsychiatric symptoms in people with dementia. CNS Drugs. 2010 Sep;24(9):729-39. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20806986 - ↑ 29.0 29.1 Porsteinsson AP et al Effect of Citalopram on Agitation in Alzheimer Disease. The CitAD Randomized Clinical Trial. JAMA. 2014;311(7):682-691 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24549548 https://jama.jamanetwork.com/article.aspx?articleid=1829989
Small GW Treating Dementia and Agitation. JAMA. 2014;311(7):677-678 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24549545 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1829969 - ↑ Iglewicz A1, Meeks TW, Jeste DV. New wine in old bottle: late-life psychosis Psychiatr Clin North Am. 2011 Jun;34(2):295-318, vii. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21536160
- ↑ 31.0 31.1 31.2 Rodda J1, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr. 2009 Oct;21(5):813-24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19538824
- ↑ 32.0 32.1 32.2 32.3 32.4 32.5 32.6 32.7 32.8 32.9 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ Weintraub D, Hurtig HI. Presentation and management of psychosis in Parkinson's disease and dementia with Lewy bodies. Am J Psychiatry. 2007 Oct;164(10):1491-8. Review. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17898337
- ↑ 34.0 34.1 Brodaty H, Arasaratnam C. Review: Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry. 2012;169:946-953 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22952073
- ↑ Ballard C, Brown R, Fossey J et al Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial). Am J Geriatr Psychiatry. 2009 Sep;17(9):726-33. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19700946
- ↑ Gitlin LN, Winter L, Dennis MP, Hodgson N, Hauck WW. Targeting and managing behavioral symptoms in individuals with dementia: a randomized trial of a nonpharmacological intervention. J Am Geriatr Soc. 2010 Aug;58(8):1465-74. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20662955
- ↑ 37.0 37.1 Chen Y, Briesacher BA, Field TS, Tjia J, Lau DT, Gurwitz JH. Unexplained variation across US nursing homes in antipsychotic prescribing rates. Arch Intern Med. 2010 Jan 11;170(1):89-95 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20065204
- ↑ 38.0 38.1 Kamble P, Chen H, Sherer JT, Aparasu RR. Use of antipsychotics among elderly nursing home residents with dementia in the US: an analysis of National Survey Data. Drugs Aging. 2009;26(6):483-92. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19591523
- ↑ 39.0 39.1 Lester P, Kohen I, Stefanacci RG, Feuerman M. Antipsychotic drug use since the FDA black box warning: survey of nursing home policies. J Am Med Dir Assoc. 2011 Oct;12(8):573-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21450177
- ↑ 40.0 40.1 Lonergan E, Luxenberg J. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD003945. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19588348
- ↑ Salzman C, Jeste DV, Meyer RE et al Elderly patients with dementia-related symptoms of severe agitation and aggression: consensus statement on treatment options, clinical trials methodology, and policy. J Clin Psychiatry. 2008 Jun;69(6):889-98. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18494535
- ↑ 42.0 42.1 42.2 Prescriber's Letter 21(6): 2014 Preventing and Treating Delirium in Inpatients Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300612&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Choosing Wisely: Five Things Physicians and Patients Should Question. An Initiative of the ABIM Foundation. American Geriatrics Society http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clinical_guidelines_recommendations/choosingwisely
- ↑ 44.0 44.1 44.2 44.3 Cohen-Mansfield J, Thein K, Marx MS, et al. Sources of discomfort in persons with dementia. JAMA Intern Med. 2013;173(14):1378-1379 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23877083
- ↑ 45.0 45.1 Cummings JL. Lyketsos CG, Peskind ER et al Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia. A Randomized Clinical Trial. JAMA. 2015;314(12):1242-1254 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26393847 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2442936
Ballard C, Sharp S, Anne Corbett A Dextromethorphan and Quinidine for Treating Agitation in Patients With Alzheimer Disease Dementia JAMA. 2015;314(12):1233-1235. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26393843 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2442913 - ↑ 46.0 46.1 46.2 46.3 46.4 Medical Knowledge Self Assessment Program (MKSAP) 17, 19 American College of Physicians, Philadelphia 2015, 2021
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Barr J, Fraser GL, Puntillo K et al Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23269131
- ↑ 48.0 48.1 Ballard C et al. Impact of antipsychotic review and nonpharmacological intervention on antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: A factorial cluster-randomized controlled trial by the Well-Being and Health for People with Dementia (WHELD) program. Am J Psychiatry 2015 Nov 20; PMID: https://www.ncbi.nlm.nih.gov/pubmed/26585409
- ↑ Corbett A, Burns A, Ballard C. Don't use antipsychotics routinely to treat agitation and aggression in people with dementia. BMJ. 2014;349:g6420 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25368388
- ↑ 50.0 50.1 Schneider LS et al. Heterogeneity of treatment response to citalopram for patients with Alzheimer's disease with aggression or agitation: The CitAD randomized clinical trial. Am J Psychiatry 2016 Jan 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26771737 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15050648
- ↑ Agency for Healthcare Research and Quality (AHRQ) Executive Summary. March 21, 2016 Nonpharmacologic Interventions for Agitation and Aggression in Dementia. https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2198
- ↑ 52.0 52.1 Reus VI, Fochtmann LJ, Eyler AE et al The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. Am J Psychiatry. 2016 May 1;173(5):543-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27133416
- ↑ Reinhardt MM, Cohen CI. Late-life psychosis: diagnosis and treatment. Curr Psychiatry Rep. 2015 Feb;17(2):1. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25617038
- ↑ Steinberg M, Lyketsos CG. Atypical antipsychotic use in patients with dementia: managing safety concerns. Am J Psychiatry. 2012 Sep;169(9):900-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22952071 Free PMC Article
- ↑ Rossom RC, Rector TS, Lederle FA, Dysken MW. Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia? J Am Geriatr Soc. 2010 Jun;58(6):1027-34. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20487081
- ↑ Kales HC, Gitlin LN, Lyketsos CG et al Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc. 2014 Apr;62(4):762-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24635665 Free PMC Article
- ↑ 57.0 57.1 Patel AN, Lee S, Andrews HF et al. Prediction of relapse after discontinuation of antipsychotic treatment in Alzheimer's disease: The role of hallucinations. Am J Psychiatry 2016 Nov 18; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27855483
- ↑ 58.0 58.1 Agar MR, Lawlor PG, Quinn S et al Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care. A Randomized Clinical Trial. JAMA Intern Med. Published online December 5, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27918778 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2588810
- ↑ 59.0 59.1 Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015 Mar 2;350:h369 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25731881
- ↑ Pieper MJ, Francke AL, van der Steen JT, et al. Effects of a stepwise multidisciplinary intervention for challenging behavior in advanced dementia: a cluster randomized controlled trial. J Am Geriatr Soc. 2016;64(2):261-269 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26804064
- ↑ Livingston G, Kelly L, Lewis-Holmes E, et al. Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials. Br J Psychiatry. 2014;205(6):436-442 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25452601 Free full text
- ↑ Lim LS. ACP Journal Club. Review: In patients with dementia who live in care homes, some nondrug interventions reduce agitation. Ann Intern Med. 2015 Jun 16;162(12):JC3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26075780
- ↑ 63.0 63.1 Herzig SJ, LaSalvia MT, Naidus E et al. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: A cohort study. J Am Geriatr Soc 2017 Dec; 65:2580. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29095482 https://doi.org/10.1111/jgs.15066
- ↑ 64.0 64.1 64.2 NEJM Question of the Week. Feb 27, 2018 https://knowledgeplus.nejm.org/question-of-week/1616/
- ↑ 65.0 65.1 Ballard C, Corbett A, Orrell M et al Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: A cluster-randomised controlled trial. PLoS Medicine. February 6, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29408901 Free PMC Article <Internet> http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002500
- ↑ 66.0 66.1 Maust DT, Kim HM, Chiang C et al Association of the Centers for Medicare & Medicaid Services' National Partnership to Improve Dementia Care With the Use of Antipsychotics and Other Psychotropics in Long-term Care in the United States From 2009 to 2014. JAMA Intern Med. Published online March 17, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29550856 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2674245
- ↑ 67.0 67.1 67.2 Park Y, Bateman BT, Kim DH, et al Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study. BMJ 2018;360:k1218 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29592958 https://www.bmj.com/content/360/bmj.k1218
- ↑ 68.0 68.1 Monaco K Nabilone Effective for Easing Agitation in Alzheimer's - Cognition, neuropsychiatric symptoms also improved with synthetic cannabinoid. MedPage Today. July 25, 2018 https://www.medpagetoday.com/meetingcoverage/aaic/74214
Lanctot K, et al Nabilone significantly improves agitation/aggression in patients with moderate-to-severe AD: Preliminary results of a placebo- controlled, double-blind, cross-over trial. Alzheimer's Association International Conference (AAIC) 2018; Abstract F4-02-04. - ↑ 69.0 69.1 Watt JA, Goodarzi Z, Veroniki AA et al Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2019. Oct 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31610547 https://annals.org/aim/article-abstract/2753018/comparative-efficacy-interventions-aggressive-agitated-behaviors-dementia-systematic-review-network
- ↑ 70.0 70.1 Monaco K Trial: Drug Induces, Maintains Dementia-Related Psychosis Remission - Results pave way for Nuplazid label expansion. MedPage Today September 14, 2020 https://www.medpagetoday.com/meetingcoverage/psychcongress/88607
Foff E, et al Pimavanserin significantly reduces risk of relapse of dementia-related psychosis: results from the double-blind phase of the HARMONY study. Psych Congress 2020; Poster #187
Foff E, et al Response to pimavanserin treatment in patients with dementia-related psychosis: results From the 12-week, open-label phase of the HARMONY study. Psych Congress 2020; Poster #197
Grant K Staying on Pimavanserin Cut Dementia-Related Psychosis Relapse. However, late-stage trial couldn't separate efficacy in dementia subtypes. MedPage Today July 21, 2021 https://www.medpagetoday.com/psychiatry/dementia/93689
Tariot PN, Cummings JL, Soto-Martin ME et al Trial of pimavanserin in dementia-related psychosis. N Engl J Med 2021; 385:309-319, July 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34289275 https://www.nejm.org/doi/full/10.1056/NEJMoa2034634
Friedman JI Pimavanserin in dementia-related psychosis. N Engl J Med 2021; 385:372-373. July 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34289282 https://www.nejm.org/doi/full/10.1056/NEJMe2109010 - ↑ 71.0 71.1 Anderson P Cannabinoids 'Worth a Try' for Agitation in Alzheimer's Medscape - Feb 02, 2021. https://www.medscape.com/viewarticle/945163
Outen JD, Burhanullah MH, Vandrey R et al Cannabinoids for Agitation in Alzheimer's Disease. Am J Geriatr Psychiatry 2021. Jan 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33573996 https://www.ajgponline.org/article/S1064-7481(21)00030-0/fulltext - ↑ 72.0 72.1 Tumolo J Dementia-Related Psychosis Presents Significant Cost Burden Annals of Long-Term Care. June 22, 2021 https://www.hmpgloballearningnetwork.com/site/altc/news/dementia-related-psychosis-presents-significant-cost-burden
Sangha K, Rashid N, Abler V, Rajagopalan K. Economic Burden of Dementia Related Psychosis Among Medicare Beneficiaries: A State-Transition Markov Analysis of Total Annual Direct Costs. CNS Spectr. 2021;26(2):161. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34127102 - ↑ 73.0 73.1 Long EM Case Report and Brief Review. The Effect of a Personalized Music Playlist on a Patient With Dementia and Evening Agitation. Annals of Long-Term Care. December 2016 https://www.hmpgloballearningnetwork.com/site/altc/article/effect-personalized-music-playlist-patient-dementia-and-evening-agitation
- ↑ 74.0 74.1 Banerjee S, High J, Stirling S et al Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial. Lancet. 2021 398(10310):1487-1497. October 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34688369 PMCID: PMC8546216 Free PMC article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01210-1/fulltext#%20
- ↑ Talebraza S et al Geriatrics Evaluation & Management Tools American Geriatrics Society. 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34688369 https://geriatricscareonline.org/ProductAbstract/geriatrics-evaluation-management-tools/B007/
- ↑ 76.0 76.1 Asimopoulos M Doll Therapy Reduced Dementia Symptoms, Caregiver Burden. Annals of Long-Term Care. November 12, 2021 https://www.hmpgloballearningnetwork.com/site/altc/news/doll-therapy-reduced-dementia-symptoms-caregiver-burden
Santagata F, Massaia M, D'Amelio P The doll therapy as a first line treatment for behavioral and psychologic symptoms of dementia in nursing homes residents: a randomized, controlled study. BMC Geriatr. 2021 Oct 12;21(1):545 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34641791 PMCID: PMC8507228 Free PMC article - ↑ Muhlbauer V, Mohler R, Dichter MN et al Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews. December 17, 2021 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013304.pub2/full
- ↑ 78.0 78.1 78.2 78.3 Ismail Z, Creese B, Aarsland D et al Psychosis in Alzheimer disease - mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol 2022. January 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34983978 Review. https://www.nature.com/articles/s41582-021-00597-3
- ↑ 79.0 79.1 79.2 79.3 79.4 Watt JA, Thompson W, Marple R et al Managing neuropsychiatric symptoms in patients with dementia. BMJ 2022;376:e069187 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35078774 https://www.bmj.com/content/376/bmj-2021-069187
- ↑ 80.0 80.1 Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006 Oct;81(10):1361-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17036562 Review.
- ↑ Rothenberg KG, Rajaram R. Advances in management of psychosis in neurodegenerative diseases. Curr Treat Options Neurol. 2019;21(1):3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30673880 Review. https://link.springer.com/article/10.1007/s11940-019-0545-6
- ↑ Fleisher AS, Truran D, Mai JT et al. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology. 2011;77(13):1263-1271 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21917762 PMCID: PMC3179645 Free PMC article https://n.neurology.org/content/77/13/1263
- ↑ Sarycheva T, Lavikainen P, Taipale H et al. Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease. Neurology. 2020;94(20):e2099-e2108 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32327491 PMCID: PMC7526675 Free PMC article https://n.neurology.org/content/94/20/e2099
- ↑ Taipale H, Gomm W, Broich K et al. Use of Antiepileptic Drugs and Dementia Risk-an Analysis of Finnish Health Register and German Health Insurance Data. J Am Geriatr Soc. 2018;66(6):1123-1129 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29566430 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.15358
- ↑ 85.0 85.1 DePeau-Wilson M FDA Advisors Endorse Rexulti for Agitation in Alzheimer's Dementia. Increased mortality risk seen but benefits may outweigh this, panelists say MedPage Today April 14, 2023 https://www.medpagetoday.com/psychiatry/dementia/104041
US Food & Drug Administration News Release. May 11, 2023 FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer's Disease. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease - ↑ 86.0 86.1 86.2 NEJM Knowledge+ Question of the Week May 23, 2023 https://knowledgeplus.nejm.org/question-of-week/2143/
van Dalen-Kok AH, Pieper MJ, de Waal MW, Lukas A, Husebo BS, Achterberg WP. BMC Geriatr. 2015 Apr 19;15:49. Association between pain, neuropsychiatric symptoms, and physical function in dementia: a systematic review and meta-analysis. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25928621 PMCID: PMC4409739 Free PMC article
Lobbezoo F, Delwel S, Weijenberg RAF, Scherder EJA. Orofacial Pain and Mastication in Dementia. Curr Alzheimer Res. 2017;14(5):506-511 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28490315 Review
Marchini L, Ettinger R, Caprio T, Jucan A. Oral health care for patients with Alzheimer's disease: An update. Spec Care Dentist. 2019 May;39(3):262-273. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30964560 - ↑ 87.0 87.1 Huang YY, Teng T, Giovane CD et al. Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis. Age Ageing. 2023 Jun 1;52(6):afad091 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37381843
- ↑ 88.0 88.1 88.2 d'Angremont E, Begemann MJH, van Laar T et al Cholinesterase Inhibitors for Treatment of Psychotic Symptoms in Alzheimer Disease and Parkinson Disease. A Meta-analysis. JAMA Neurol. 2023;80(8):813-823 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37358841 PMCID: PMC10294019 (available on 2024-06-26) https://jamanetwork.com/journals/jamaneurology/fullarticle/2806600
- ↑ 89.0 89.1 89.2 Luhnen J, Richter T, Calo S, et al. Psychosocial interventions for reducing antipsychotic medication in care home residents. Cochrane Database Syst Rev. 2023 Aug 31;8(8):CD008634. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37650479 PMCID: PMC10471006 (available on 2024-08-31) https://journalwise.acponline.org/Articles/SpecialtyAlert/110639
- ↑ 90.0 90.1 Ishimaru D, Tanaka H, Nagata Y, Ogawa Y, Fukuhara K, Nishikawa T. Aspects of Rest-Activity Rhythms Associated With Behavioral and Psychological Symptoms in Moderate and Severe Dementia, Results of a Cross-sectional Analysis. Alzheimer Dis Assoc Disord. 2023 Oct 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37824629 https://journals.lww.com/alzheimerjournal/abstract/9900/aspects_of_rest_activity_rhythms_associated_with.80.aspx
- ↑ 91.0 91.1 Lee D, Slomkowski M, Hefting N et al. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial. JAMA Neurol. 2023 Nov 6:e233810. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37930669 PMCID: PMC10628834 Free PMC article
- ↑ 92.0 92.1 92.2 NEJM Knowledge+
- ↑ 93.0 93.1 Rane A et al Comparative Efficacy and Safety of Pharmacological Interventions in Patients with Dementia-Related Agitation or Aggression: A Network Meta-Analysis. Am J Geriatr Psychiatry 2024. 32(4):S95 Not yet indexed in PubMed https://www.sciencedirect.com/science/article/abs/pii/S106474812400188X