Therapeutic dilemma's: antipsychotics use for neuropsychiatric symptoms of dementia, delirium and insomnia and risk of falling in older adults, a clinical review
Language English Country Switzerland Media print-electronic
Document type Journal Article, Review, Research Support, Non-U.S. Gov't
PubMed
37495836
PubMed Central
PMC10447285
DOI
10.1007/s41999-023-00837-3
PII: 10.1007/s41999-023-00837-3
Knihovny.cz E-resources
- Keywords
- Antipsychotics, Delirium, Dementia, Falls, Insomnia, Older adults,
- MeSH
- Antipsychotic Agents * adverse effects MeSH
- Delirium * chemically induced drug therapy MeSH
- Dementia * drug therapy chemically induced MeSH
- Humans MeSH
- Sleep Initiation and Maintenance Disorders * chemically induced drug therapy MeSH
- Aged MeSH
- Accidental Falls prevention & control MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antipsychotic Agents * MeSH
PURPOSE: Because of the common and increasing use of antipsychotics in older adults, we aim to summarize the current knowledge on the causes of antipsychotic-related risk of falls in older adults. We also aim to provide information on the use of antipsychotics in dementia, delirium and insomnia, their adverse effects and an overview of the pharmacokinetic and pharmacodynamic mechanisms associated with antipsychotic use and falls. Finally, we aim to provide information to clinicians for weighing the benefits and harms of (de)prescribing. METHODS: A literature search was executed in CINAHL, PubMed and Scopus in March 2022 to identify studies focusing on fall-related adverse effects of the antipsychotic use in older adults. We focused on the antipsychotic use for neuropsychiatric symptoms of dementia, insomnia, and delirium. RESULTS: Antipsychotics increase the risk of falls through anticholinergic, orthostatic and extrapyramidal effects, sedation, and adverse effects on cardio- and cerebrovascular system. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antipsychotics without current indication. CONCLUSIONS: Deprescribing of antipsychotics should be considered and encouraged in older people at risk of falling, especially when prescribed for neuropsychiatric symptoms of dementia, delirium or insomnia. If antipsychotics are still needed, we recommend that the benefits and harms of antipsychotic use should be reassessed within two to four weeks of prescription. If the use of antipsychotic causes more harm than benefit, the deprescribing process should be started.
Hospital General Universitario de Ciudad Real Ciudad Real Spain
School of Pharmacy University of Eastern Finland Kuopio Finland
See more in PubMed
Shireen E. Experimental treatment of antipsychotic-induced movement disorders. J Experiment Pharmacol. 2016 doi: 10.2147/JEP.S63553. PubMed DOI PMC
Hollister LE (2000) Psychiatric disorders. In: Melmon and Morelli’s Clinical Pharmacology, editors. 4th edn. The United States of America, pp 429–528
Seppälä LJ, Wermelink AMAT, de Vries M, et al. Fall-risk-increasing drugs: a systematic review and meta-analysis: II. Psychotropics. J Am Med Dir Assoc. 2018 doi: 10.1016/j.jamda.2017.12.098. PubMed DOI
Olfson M, King M, Schoenbaum M. Antipsychotic treatment of adults in The United States. J Clin Psychiatry. 2015 doi: 10.4088/JCP.15m09863. PubMed DOI
Alanen HM, Finne-Soveri H, Fialova D, et al. Use of antipsychotic medications in older home-care patients report From Nine European countries. Aging Clin Exp Res. 2008 doi: 10.1007/bf03324781. PubMed DOI
Onder G, Liperoti R, Fialova D, et al. Polypharmacy in nursing home in Europe: results from the SHELTER study. J Gerontol A Biol Sci Med Sci. 2012 doi: 10.1093/gerona/glr233. PubMed DOI
Vetrano DL, Tosato M, Colloca G, et al. Polypharmacy in nursing home residents with severe cognitive impairment: results from the SHELTER study. Alzheimers Dement. 2013 doi: 10.1016/j.jalz.2012.09.009. PubMed DOI
CIHI (2021) Potentially inappropriate use of antipsychotics long-term care. In Your Health System: Canadian Institute for Health Information (CIHI). https://yourhealthsystem.cihi.ca/hsp/inbrief?lang=en#!/indicators/008/potentially-inappropriate-use-of-antipsychotics-in-long-term-care/;mapC1;mapLevel2;overview. Accessed 11 Aug 2022
Dementia (2021) World Health Organization. https://www.who.int/news-room/fact-sheets/detail/dementia Accessed 5 Jul 2022
Finnish Medical Society Duodecim. Finnish Current Care Guidelines for Memory Disorders. Duodecim. https://www.kaypahoito.fi/hoi50044. Accessed 14 Jul 2022
Kuronen M, Kautiainen H, Karppi P, et al. antipsychotic drug use and associations with neuropsychiatric symptoms in persons with impaired cognition: a cross-sectional study. Nord J Psychiatry. 2016 doi: 10.1080/08039488.2016.1191537. PubMed DOI
Capiau A, Foubert K, Somers A, et al. Guidance for appropriate use of psychotropic drugs in older people. Eur Geriatr Med. 2021 doi: 10.1007/s41999-020-00439-3. PubMed DOI
Orsel K, Taipale H, Tolppanen A-M, et al. Psychotropic drugs use and psychotropic polypharmacy among persons with Alzheimer’s disease. Eur Neuropsychopharmacol. 2018 doi: 10.1016/j.euroneuro.2018.04.005. PubMed DOI
Koponen M, Tolppanen AM, Taipale H, et al. Incidence of antipsychotics use in relation to diagnosis of Alzheimer’s disease among community-dwelling persons. Br J Psych. 2015;207(5):444–449. doi: 10.1192/bjp.bp.114.162834. PubMed DOI
Koponen M, Taipale H, Tanskanen A, et al. Long-term use of antipsychotics among community-dwelling persons with Alzheimer’s disease: a nationwide register-based study. Eur Neuropsychopharmacol. 2015 doi: 10.1016/j.euroneuro.2015.07.008. PubMed DOI
Stubbs B, Perara G, Koyanagi A, et al. Risk of hospitalized falls and hip fractures in 22,103 older adults receiving mental health care vs 161,603 controls: a large cohort study. J Am Med Dir Assoc. 2020 doi: 10.1016/j.jamda.2020.03.005. PubMed DOI PMC
Tolppanen A-M, Lavikainen P, Soininen H, et al. Incident hip fractures among community dwelling persons with Alzheimer’s disease in a finnish nationwide register-based cohort. PLoS ONE. 2013 doi: 10.1371/journal.pone.0059124. PubMed DOI PMC
Silva LOJE, Berning MJ, Stanich JA, et al. Risk factors for delirium in older adults in the emergency department: a systematic review and meta-analysis. Ann Emerg Med. 2021 doi: 10.1016/j.annemergmed.2021.03.005. PubMed DOI
Han QYC, Rodrigues NG, Klainin-Yobas P, et al. Prevalence, risk factors, and impact of delirium on hospitalized older adults with dementia: a systematic review and meta-analysis. J Am Med Dir Assoc. 2022 doi: 10.1016/j.jamda.2021.09.008. PubMed DOI
Oren G, Jolkovsky S, Tal S. Falls in oldest-old adults hospitalized in acute geriatric ward. Eur Geriatr Med. 2022;13(4):859–866. doi: 10.1007/s41999-022-00660-2. PubMed DOI
Witlox J, Eurelings LSM, Se Jonghe JFM, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia. JAMA. 2010 doi: 10.1001/jama.2010.1013. PubMed DOI
Swan JT, Fitousis K, Hall JB, et al. Antipsychotic use and diagnosis of delirium in the intensive care unit. Crit Care. 2012 doi: 10.1186/cc11342. PubMed DOI PMC
Egberts A, Alan H, Ziere G, et al. Antipsychotics and lorazepam during delirium: are we harming older patients? A real-life data study. Drugs Aging. 2021 doi: 10.1007/s40266-020-00813-7. PubMed DOI PMC
Neufeld KJ, Yue J, Robinson TN, et al. antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016 doi: 10.1111/jgs.14076. PubMed DOI PMC
Nguyen V, George T, Brewster GS. Insomnia in older adults. Curr Geriatr Rep. 2019 doi: 10.1007/s13670-019-00300-x. PubMed DOI PMC
Vieira ER, Freund-Heritage R, da Costa BR (2021) Risk factors for geriatric patient falls in rehabilitation hospital settings: a systematic review. Clin Rehabil. 10.1177/0269215511400639 PubMed
Wennberg AMV, Wu MN, Rosenberg PB, et al. Sleep disturbance, cognitive decline, and dementia: a review. Semin Neurol. 2018 doi: 10.1055/s-0037-1604351. PubMed DOI PMC
Pop P, Bronskill SE, Piggott KL, et al. Management of sleep disorders in community-dwelling older women and men at the time of diagnosis. J Am Geriatr Soc. 2019 doi: 10.1111/jgs.16038. PubMed DOI
Seppälä LJ, van der Velde N, Masud T, et al. The EuGMS task and finish group on fall-risk-increasing drugs (FRIDs): position on knowledge dissemination, management, and future research. Drugs Aging. 2019 doi: 10.1007/s40266-018-0622-7. PubMed DOI PMC
Montero-Odasso M, van der Velde N, Martin FC, et al. Task force on global guidelines for falls in older adults: world guidelines for falls prevention and management for older adults: a global initiative. Age Ageing. 2022;51:afac205. doi: 10.1093/ageing/afac205. PubMed DOI PMC
Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med. 2015;175:827. doi: 10.1001/jamainternmed.2015.0324. PubMed DOI
Christian R, Saavedra L, Gaynes BN et al (2012) Appendix A: tables of FDA-approved indications for first- and second-generation antipsychotics. In: Future research needs for first- and second-generation antipsychotics for children and young adults. Agency for Healthcare Research and Quality, Rockville PubMed
Risperidal. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/referrals/risperdal. Accessed 8 Jul 2022
Kishi T, Hirota T, Matsunaga S, et al. antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2015 doi: 10.1136/jnnp-2015-311049. PubMed DOI
Igsleder B, Frühwald T, Jagsch C, et al. Delirium in geriatric patients. Wien Med Wochenschr. 2022 doi: 10.1007/s10354-021-00904-z. PubMed DOI PMC
Schroeck JL, Ford J, Conway EL, et al. Review of safety and efficacy of sleep medicines in older adults. Clin Ther. 2016 doi: 10.1016/j.clinthera.2016.09.010. PubMed DOI
Atkin T, Comai S, Gobbi G, et al. Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharmacol Rev. 2018 doi: 10.1124/pr.117.014381. PubMed DOI
Thompson W, Quay TAW, Rojas-Fernandez C, et al. Atypical antipsychotics for insomnia: a systematic review. Sleep Med. 2016 doi: 10.1016/j.sleep.2016.04.003. PubMed DOI
Van Straten A, Van der Zweerde T, Kleiboer A, et al. Cognitive and behavioral therapies in the treatment of insomnia: a meta-analysis. Sleep Med Rev. 2018 doi: 10.1016/j.smrv.2017.02.001. PubMed DOI
Phan SV, Osae S, Morgan JC, et al. Neuropsychiatric symptoms in dementia: considerations for pharmacotherapy in the USA. Drugs R D. 2019 doi: 10.1007/s40268-019-0272-1. PubMed DOI PMC
O’Mahony D, O’Sullivan D, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015 doi: 10.1093/ageing/afu145. PubMed DOI PMC
Beers criteria (DDIs): Fick DM, Semla TP, Steinman M, et al (2019) American geriatrics society 2019 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 10.1111/jgs.15767 PubMed
Seppala LJ, Petrovic M, Ryg J, et al. STOPPFall (screening tool of older persons prescriptions in older adults with high fall risk): a Delphi study by the EuGMS task and finish group on fall-risk-increasing drugs. Age Ageing. 2021 doi: 10.1093/ageing/afaa249. PubMed DOI PMC
The American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults (2015) American geriatrics society abstracted clinical practice guideline for postoperative delirium in older adults. JAGS. 10.1111/jgs.13281 PubMed PMC
The National Institute for Health and Care Excellence (2019) Delirium: prevention, diagnosis and management. https://www.nice.org.uk/guidance/cg103/chapter/Recommendations#treating-delirium. Accessed 31 Aug 2022
Koopmans AB, Braakman MH, Vinkers DJ, et al. Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19. Transl Psychiatry. 2021 doi: 10.1038/s41398-020-01129-1. PubMed DOI PMC
Wijesinghe R. A review of pharmacokinetic and pharmacodynamic interactions with antipsychotics. Ment Health Clin. 2016 doi: 10.9740/mhc.2016.01.021. PubMed DOI PMC
The Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 12 Jul 2022
Clozapine tablet (Package insert). Sun Pharmaceutical Industries. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=53bdb79c-c4cf-4818-b1f0-225e67a14536. Accessed 17 Mar 2021
Yunusa I, Alsumali A, Garba AE, et al. Assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia. JAMA Netw Open. 2019 doi: 10.1001/jamanetworkopen.2019.0828. PubMed DOI PMC
Maher AR, Maglione M, Bagley S. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults. JAMA. 2011 doi: 10.1001/jama.2011.1360. PubMed DOI
US Food and Drug Administration. Public Health Advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. https://wayback.archive-it.org/7993/20170113112252/http:/www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm053171.htm. Accessed 22 Jun 2022
EMA boxed warning: European Medicines Agency (EMA) (2008) CHMP assessment report on conventional antipsychotics. procedure under article 5(3) of regulation (EC) No 726/2004. EMEA/CHMP/590557/2008. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/01/WC500054057.pdf. Accessed 8 Jul 2022
US Food and Drug Administration. Information for healthcare professionals: conventional antipsychotics. https://wayback.archive-it.org/7993/20170722190727/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm. Accessed 22 Jun 2022
Koponen M, Rajamäki B, Lavikainen P, et al. Antipsychotic use and risk of stroke among community-dwelling people with Alzheimer’s disease. J Am Med Dir Assoc. 2021 doi: 10.1016/j.jamda.2021.09.036. PubMed DOI
Yu ZH, Jiang HY, Shao L, et al. Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016 doi: 10.1111/bcp.12985. PubMed DOI PMC
Koponen M, Taipale H, Lavikainen P, et al. Risk of mortality associated with antipsychotic monotherapy and polypharmacy among community-dwelling persons with Alzheimer’s disease. J Alzheimer’s Dis. 2017 doi: 10.3233/JAD-160671. PubMed DOI
Yunusa I, Rashid N, Demos GN, et al. Comparative outcomes of commonly used off-label atypical antipsychotics in the treatment of dementia-related psychosis: a network meta-analysis. Adv Ther. 2022 doi: 10.1007/s12325-022-02075-8. PubMed DOI PMC
Dennis M, Shine L, John A, et al. Risk of adverse outcomes for older people with dementia prescribed antipsychotic medication: a population based e-cohort study. Neurol Ther. 2017 doi: 10.1007/s40120-016-0060-6. PubMed DOI PMC
Shin J-Y, Choi N-K, Lee J, et al. A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis. J Psychopharmacol. 2015 doi: 10.1177/0269881115578162. PubMed DOI
Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017 doi: 10.2147/2FTCRM.S117321. PubMed DOI PMC
Gareri P, De Fazio P, Manfredi VGLM, et al. Use and safety of antipsychotics in behavioral disorders in elderly people with dementia. J Clin Psychopharmacol. 2014 doi: 10.1097/JCP.0b013e3182a6096e. PubMed DOI
Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension. CNS Drugs. 2012 doi: 10.2165/11591710-000000000-00000. PubMed DOI
Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimer’s Dis. 2014 doi: 10.3233/JAD-140579. PubMed DOI
Mortensen SJ, Mohamadi A, Wright C, et al. Medications as a risk factor for fragility hip fractures: a systematic review and meta-analysis. Calcified Tissue Int. 2020 doi: 10.1007/s00223-020-00688-1. PubMed DOI
Koponen M, Taipale H, Lavikainen P, et al. Antipsychotic use and the risk of hip fracture among community-dwelling persons with Alzheimer’s disease. J Clin Psychiatry. 2017 doi: 10.4088/JCP.15m10458. PubMed DOI
Tapiainen V, Lavikainen P, Koponen M, et al. The risk of head injuries associated with antipsychotic use among persons with Alzheimer’s disease. J Am Geriatr Soc. 2020 doi: 10.1111/jgs.16275. PubMed DOI
American Psychiatric Association (2016) The American Psychiatric Association Practice Guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. American Psychiatric Association, Washington, DC. 10.1176/appi.books.9780890426807
Guideline Adaption Committee (2022) Clinical practice guidelines and principles of care for people with dementia. https://cdpc.sydney.edu.au/wp-content/uploads/2019/06/Dementia-Guideline-Recommendations-WEB-version.pdf. Accessed 12 Jul 2022
MedStopper (2022) https://medstopper.com/. Accessed 3 Aug 2022
Desprescribing.org (2022) https://deprescribing.org/. Accessed 3 Aug 2022
Decision tree (2022) https://kik.amc.nl/falls/decision-tree/. Accessed 3 Aug 2022
Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med. 2015 doi: 10.1001/jamainternmed.2015.0324. PubMed DOI
Simmons SF, Bonnett KR, Hollingswoth E, et al. Reducing antipsychotic medication use in nursing homes: a qualitative study of nursing staff perceptions. Gerontologist. 2018 doi: 10.1093/geront/gnx083. PubMed DOI