THIS DOI METADATA WAS LAST UPDATED: 2024-01-10 22:57
Full Title
RIVISTA SPERIMENTALE DI FRENIATRIA
Publisher
FrancoAngeli
ISSN
1129-6437 (Printed Journal)
1972-5582 (Online Journal)
Journal Issue Number
2
Journal Issue Designation
2
Journal Issue Date (YYYY/MM)
2016/07
Full Title
Rischio di mortalità con i farmaci antipsicotici nella popolazione psichiatrica anziana? Una revisione sistematica della letteratura
By (author)
First Page
127
Last Page
150
Language of text
Italian
Publication Date
2016/07
Copyright
2016 FrancoAngeli srl
Introduction or preface
In Italia gli anziani raggiungono quasi un quarto della popolazione generale. In questo sottogruppo, gli antipsicotici sono ampiamente prescritti: nonostante siano autorizzati esclusivamente per schizofrenia e disturbo bipolare, è assai frequente l'uso off-label in demenza, delirium, ed altri disturbi. Un'ampia letteratura ha osservato un'associazione tra rischio di mortalità ed esposizione ad antipsicotici nella popolazione anziana con demenza, supportando la pubblicazione di black box warnings da parte della Food and Drug Administration negli Stati Uniti, secondo un percorso poi seguito dagli altri Paesi. Tuttavia, non è chiaro se tale associazione sia causale, così come se sia applicabile anche a pazienti anziani non affetti da demenza. Questo studio si pone l'obiettivo di revisionare sistematicamente la letteratura riguardante il rischio di mortalità nella popolazione geriatrica affetta da psicosi dello spettro schizofrenico e bipolare, demenza e delirium. È stata condotta una ricerca sistematica sui database MEDLINE e Cochrane Library, includendo quegli studi riguardanti la valutazione del rischio di mortalità in soggetti di 65 o più anni trattati con antipsicotici di prima e/o seconda generazione. In totale, 25 pubblicazioni soddisfacevano i criteri d'inclusione per questa revisione sistematica: 3 per psicosi in schizofrenia e disturbo bipolare, 20 per demenze, e 2 per delirium. Sebbene non sia possibile rifiutare l'ipotesi di un soggiacente meccanismo fisiopatologico comune alla condizione "vecchiaia", comportante un maggiore rischio di mortalità a seguito dell'esposizione a farmaci antipsicotici, è innegabile che anche la patologia neuropsichiatrica di base abbia una sua influenza, sia essa positiva o negativa, su tale rapporto. La corretta valutazione dei fattori di rischio individuali può aiutare a prendere decisioni condivise tra clinico e paziente verso scelte terapeutiche più efficaci, sicure, e soprattutto più appropriate.
Unstructured Citation
[1] ISTAT Istituto nazionale di statistica. Il futuro demografico del Paese. Internet 2016 Available from: http://www.istat.it/it/files/2011/12/futurodemografico. pdf?title=Il+futuro+demografico+del+Paese+-+28/dic/2011+-+Testo+integrale.pdf
Unstructured Citation
[2] Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review
and meta-analysis. JAMA psychiatry 2015; 72(4): 334-341.
https://doi.org/10.1001/jamapsychiatry.2014.2502
Unstructured Citation
[3] Chesney E, Goodwin GM, Fazel S. Risks of all-cause and suicide mortality in mental disorders: a meta-review. World psychiatry
2014; 13(2): 153-160.
https://doi.org/10.1002/wps.20128
Unstructured Citation
[4] Osborn D, Levy G, Nazareth I, King M. Suicide and severe mental illnesses. Cohort study within the UK general practice
research database. Schizophrenia research 2008; 99(1-3): 134-138.
https://doi.org/10.1016/j.schres.2007.11.025
Unstructured Citation
[5] Maj M. Physical health care in persons with severe mental illness: a public health and ethical priority. World psychiatry
2009; 8(1): 1-2.
https://doi.org/10.1002/j.2051-5545.2009.tb00196.x
Unstructured Citation
[6] De Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen D, Asai I, Detraux J, et al. Physical illness in patients with
severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World psychiatry 2011; 10(1):
52-77.
https://doi.org/10.1002/j.2051-5545.2011.tb00014.x
Unstructured Citation
[7] Correll CU, Detraux J, De Lepeleire J, De Hert M. Effects of antipsychotics, antidepressants and mood stabilizers on risk
for physical diseases in people with schizophrenia, depression and bipolar disorder. World psychiatry 2015; 14(2): 119-136.
https://doi.org/10.1002/wps.20204
Unstructured Citation
[8] Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. The
New England Journal of Medicine 2009; 360(3): 225-235.
https://doi.org/10.1056/NEJMoa0806994
Unstructured Citation
[9] Danielsson B, Collin J, Jonasdottir Bergman G, Borg N, Salmi P, Fastbom J. Antidepressants and antipsychotics classified
with Torsades de Pointes arrhythmia risk and mortality in older adults - a Swedish nationwide study. British journal of clinical
pharmacology 2015; 81(4): 773-783.
https://doi.org/10.1111/bcp.12829
Unstructured Citation
[10] Uchida H, Mamo DC, Mulsant BH, Pollock BG, Kapur S. Increased antipsychotic sensitivity in elderly patients: evidence and mechanisms. The Journal of clinical psychiatry 2009; 70(3): 397-405. [11] Kleijer BC, Koek HL, van Marum RJ, Jansen PAF, Egberts TCG, Heerdink ER. Risk of acute coronary syndrome in elderly users of antipsychotic drugs: a nested case-control study. Heart 2012; 98(15): 1166-1171.
Unstructured Citation
[12] Ćurković M, Dodig-Ćurković K, Erić AP, Kralik K, Pivac N. Psychotropic medications in older adults: a review. Psychiatria Danubina 2016; 28(1): 13-24.
Unstructured Citation
[13] Giron MS, Forsell Y, Bernsten C, Thorslund M, Winblad B, Fastbom J. Psychotropic drug use in elderly people with and
without dementia. International journal of geriatric psychiatry 2001; 16(9): 900-906.
https://doi.org/10.1002/gps.438
Unstructured Citation
[14] Colenda CC, Mickus MA, Marcus SC, Tanielian TL, Pincus HA. Comparison of adult and geriatric psychiatric practice patterns:
findings from the American Psychiatric Association’s Practice Research Network. The American journal of geriatric psychiatry
2002; 10(5): 609-617.
https://doi.org/10.1097/00019442-200209000-00015
Unstructured Citation
[15] Herzig SJ, Rothberg MB, Guess JR, Stevens JP, Marshall J, Gurwitz JH, Marcantonio ER. Antipsychotic use in hospitalized
adults: rates, indications, and predictors. Journal of the American Geriatrics Society 2016; 64(2): 299-305.
https://doi.org/10.1111/jgs.13943
Unstructured Citation
[16] Trifirò G, Sini G, Sturkenboom MCJM, Vanacore N, Mazzaglia G, Caputi AP, Cricelli C, et al. Prescribing pattern of antipsychotic
drugs in the Italian general population 2000-2005: a focus on elderly with dementia. International clinical psychopharmacology
2010; 25(1): 22-28.
https://doi.org/10.1097/YIC.0b013e3283334f08
Unstructured Citation
[17] Alexopoulos GS, Streim J, Carpenter D, Docherty JP. Using antipsychotic agents in older patients. The Journal of clinical psychiatry 2004; 65 Suppl 2: 5-99.
Unstructured Citation
[18] AIFA. Agenzia Italiana del Farmaco. Nota informativa sull’utilizzo di Risperidal e Belivon (risperidone) nel controllo dei sintomi comportamentali in demenza [Internet]. 2005 Available from: https://farmaci.agenziafarmaco.gov. it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000813_038250_RCP.pdf&retry=0&sys=m0b1l3
Unstructured Citation
[19] Fountoulakis KN, Nimatoudis I, Iacovides A, Kaprinis G. Off-label indications for atypical antipsychotics: A systematic
review. Annals of general hospital psychiatry 2004; 3(1): 4.
https://doi.org/10.1186/1475-2832-3-4
Unstructured Citation
[20] Weiss E, Hummer M, Koller D, Pharmd, Ulmer H, Fleischhacker WW. Offlabel use of antipsychotic drugs. Journal of clinical
psychopharmacology 2000; 20(6): 695-698.
https://doi.org/10.1097/00004714-200012000-00018
Unstructured Citation
[21] Ownby RL. Clinical trials in geriatric disorders. Current psychiatry reports 2001; 3(1): 11-12.
https://doi.org/10.1007/s11920-001-0065-3
Unstructured Citation
[22] Gardner DM, Baldessarini RJ, Waraich P. Modern antipsychotic drugs: a critical overview. CMAJ 2005; 172(13): 1703-1711.
https://doi.org/10.1503/cmaj.1041064
Unstructured Citation
[23] Jeste DV, Maglione JE. Atypical antipsychotics for older adults: are they safe and effective as we once thought? Journal of comparative effectiveness research 2013; 2(4): 355-358. [24] Jeste DV. Tardive dyskinesia rates with atypical antipsychotics in older adults. The Journal of clinical psychiatry 2004; 65, Suppl 9: 21-24.
Unstructured Citation
[25] Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophrenia research
2004; 71(2-3): 195-212.
https://doi.org/10.1016/j.schres.2004.03.024
Unstructured Citation
[26] Jeste DV, Blazer D, Casey D, Meeks T, Salzman C, Schneider L, Tariot P, et al. ACNP White Paper: update on use of antipsychotic
drugs in elderly persons with dementia. Neuropsychopharmacology 2008; 33(5): 957-970.
https://doi.org/10.1038/sj.npp.1301492
Unstructured Citation
[27] Liperoti R, Mor V, Lapane KL, Pedone C, Gambassi G, Bernabei R. The use of atypical antipsychotics in nursing homes.
The Journal of clinical psychiatry 2003; 64(9): 1106-1112.
https://doi.org/10.4088/JCP.v64n0918
Unstructured Citation
[28] CSM Committee on Safety of Medicines. Atypical antipsychotics drugs and stroke. Internet. 2004 (cited 2016 Feb 2). Available from: http://mhra.gov.uk/home/groups/plp/documents/drugsafetymessage/con019488.pdf
Unstructured Citation
[29] Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis
of randomized placebo-controlled trials. JAMA 2005; 294(15): 1934-1943.
https://doi.org/10.1001/jama.294.15.1934
Unstructured Citation
[30] US FDA Food and Drug Administration. Public health advisory: deaths with atypical antipsychotics in elderly patients with behavioural disturbances Internet. 2005 (cited 2016 Feb 2). Available from: http://www.fda.gov/Drug/DrugSafety/ucm053171.htm
Unstructured Citation
[31] Schneeweiss S, Setoguchi S, Brookhart A, Dormuth C, Wang PS. Risk of death associated with the use of conventional versus
atypical antipsychotic drugs among elderly patients. CMAJ 2007; 176(5): 627-632.
https://doi.org/10.1503/cmaj.061250
Unstructured Citation
[32] 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. The New England journal of medicine 2005; 353(22): 2335-2341.
https://doi.org/10.1056/NEJMoa052827
Unstructured Citation
[33] Nasrallah HA, White T, Nasrallah AT. Lower mortality in geriatric patients receiving risperidone and olanzapine versus
haloperidol: preliminary analysis of retrospective data. The American journal of geriatric psychiatry 2004; 12(4): 437-439.
https://doi.org/10.1097/00019442-200407000-00012
Unstructured Citation
[34] US FDA. Information for healthcare professionals: information on conventional antipsychotics. Internet. 2008 (cited 2016 Feb 2). Available from: http://www.fda.gov/Drug/DrugSafety/ucm124830.htm
Unstructured Citation
[35] Leon C, Gerretsen P, Uchida H, Suzuki T, Rajji T, Mamo DC. Sensitivity to antipsychotic drugs in older adults. Current
psychiatry reports 2010; 12(1): 28-33.
https://doi.org/10.1007/s11920-009-0080-3
Unstructured Citation
[36] Meesters PD, Comijs HC, Smit JH, Eikelenboom P, de Haan L, Beekman ATF, Stek ML. Mortality and Its Determinants in Late-Life
Schizophrenia: A 5-Year Prospective Study in a Dutch Catchment Area. The American journal of geriatric psychiatry 2016; 24(4):
272-277. [37] Straus SMJM, Bleumink GS, Dieleman JP, van der Lei J, Jong GW, Kingma JH, Sturkenboom MCJM, et al. Antipsychotics
and the risk of sudden cardiac death. Archives of internal medicine 2004; 164(12): 1293-1297.
https://doi.org/10.1001/archinte.164.12.1293
Unstructured Citation
[38] Osborn DPJ, Levy G, Nazareth I, Petersen I, Islam A, King MB. Relative risk of cardiovascular and cancer mortality in
people with severe mental illness from the United Kingdom’s General Practice Rsearch Database. Archives of general psychiatry
2007; 64(2): 242-249.
https://doi.org/10.1001/archpsyc.64.2.242
Unstructured Citation
[39] Pan Y-J, Wu C-S, Gau SS-F, Chan H-Y, Banerjee S. Antipsychotic discontinuation in patients with dementia: a systematic
review and metaanalysis of published randomized controlled studies. Dementia and geriatric cognitive disorders 2014; 37(3-4):
125-140.
https://doi.org/10.1159/000355418
Unstructured Citation
[40] Pratt N, Roughead EE, Salter A, Ryan P. Choice of observational study design impacts on measurement of antipsychotic
risks in the elderly: a systematic review. BMC medical research methodology 2012; 12(1): 72.
https://doi.org/10.1186/1471-2288-12-72
Unstructured Citation
[41] Katz I, de Deyn P-P, Mintzer J, Greenspan A, Zhu Y, Brodaty H. The efficacy and safety of risperidone in the treatment
of psychosis of Alzheimer’s disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials. International
journal of geriatric psychiatry 2007; 22(5): 475-484.
https://doi.org/10.1002/gps.1792
Unstructured Citation
[42] Haupt M, Cruz-Jentoft A, Jeste D. Mortality in elderly dementia patients treated with risperidone. Journal of clinical
psychopharmacology 2006; 26(6): 566-570.
https://doi.org/10.1097/01.jcp.0000239796.21826.39
Unstructured Citation
[43] Kryzhanovskaya LA, Jeste DV, Young CA, Polzer JP, Roddy TE, Jansen JF, Carlson JL, et al. A review of treatment-emergent
adverse events during olanzapine clinical trials in elderly patients with dementia. The Journal of clinical psychiatry 2006;
67(6): 933-945.
https://doi.org/10.4088/JCP.v67n0610
Unstructured Citation
[44] Maust DT, Kim HM, Seyfried LS, Chiang C, Kavanagh J, Schneider LS, Kales HC. Antipsychotics, other psychotropics, and
the risk of death in patients with dementia: number needed to harm. JAMA psychiatry 2015; 48109: 1-8.
https://doi.org/10.1001/jamapsychiatry.2014.3018
Unstructured Citation
[45] Jennum P, Baandrup L, Ibsen R, Kjellberg J. Increased all-cause mortality with use of psychotropic medication in dementia
patients and controls: A population-based register study. European neuropsychopharmacology 2015; 25(11): 1906-1913.
https://doi.org/10.1016/j.euroneuro.2015.08.014
Unstructured Citation
[46] Sultana J, Chang CK, Hayes RD, Broadbent M, Stewart R, Corbett A, Ballard C. Associations between risk of mortality and
atypical antipsychotic use in vascular dementia: a clinical cohort study. International journal of geriatric psychiatry 2014;
29(12): 1249-1254.
https://doi.org/10.1002/gps.4101
Unstructured Citation
[47] Piersanti M, Capannolo M, Turchetti M, Serroni N, De Berardis D, Evangelista P, Costantini P, et al. Increase in mortality rate in patients with dementia treated with atypical antipsychotics: a cohort study in outpatients in Central Italy. Rivista di psichiatria 2014; 49(1): 34-40. [48] Lopez OL, Becker JT, Chang Y-F, Sweet RA, Aizenstein H, Snitz B, Saxton J, et al. The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer’s disease. The American journal of psychiatry 2013; 170(9); 1051-1058.
Unstructured Citation
[49] Gardette V, Lapeyre-Mestre M, Coley N, Cantet C, Montastruc J-L, Vellas B, Andrieu S. Antipsychotic use and mortality
risk in community-dwelling Alzheimer’s disease patients: evidence for a role of dementia severity. Current Alzheimer research
2012; 9(9): 1106-1116.
https://doi.org/10.2174/156720512803569037
Unstructured Citation
[50] Gisev N, Hartikainen S, Chen TF, Korhonen M, Bell JS. Effect of comorbidity on the risk of death associated with antipsychotic
use among communitydwelling older adults. International psychogeriatrics 2012; 24(7): 1058-1064.
https://doi.org/10.1017/S1041610212000117
Unstructured Citation
[51] Musicco M, Palmer K, Russo A, Caltagirone C, Adorni F, Pettenati C, Bisanti L. Association between prescription of conventional
or atypical antipsychotic drugs and mortality in older persons with Alzheimer’s disease. Dementia and geriatric cognitive
disorders 2011; 31(3): 218-224.
https://doi.org/10.1159/000326213
Unstructured Citation
[52] Chan T-C, Luk JK-H, Shea Y-F, Lau K-H, Chan FH-W, Yu GK-K, Chu L-W. Continuous use of antipsychotics and its association
with mortality and hospitalization in institutionalized Chinese older adults: an 18-month prospective cohort study. International
psychogeriatrics 2011; 23(10): 1640-1648.
https://doi.org/10.1017/S104161021100175X
Unstructured Citation
[53] Rossom RC, Rector TS, Lederle FA, Dysken MW. Are all commonly prescribed antipsychotics associated with greater mortality
in elderly male veterans with dementia? Journal of the American Geriatrics Society 2010; 58(6): 1027-1034.
https://doi.org/10.1111/j.1532-5415.2010.02873.x
Unstructured Citation
[54] Simoni-Wastila L, Ryder PT, Qian J, Zuckerman IH, Shaffer T, Zhao L. Association of antipsychotic use with hospital events
and mortality among medicare beneficiaries residing in long-term care facilities. The American journal of geriatric psychiatry
2009; 17(5): 417-427.
https://doi.org/10.1097/JGP.0b013e31819b8936
Unstructured Citation
[55] Gill SS, Bronskill SE, Normand S-LT, Anderson GM, Sykora K, Lam K, Bell CM, et al. Antipsychotic drug use and mortality
in older adults with dementia. Annals of Internal Medicine 2007; 146(11): 775-786.
https://doi.org/10.7326/0003-4819-146-11-200706050-00006
Unstructured Citation
[56] 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. The American Journal of Psychiatry 2007; 164(10): 1568-1576.
https://doi.org/10.1176/appi.ajp.2007.06101710
Unstructured Citation
[57] Trifirò G, Verhamme KMC, Ziere G, Caputi AP, Ch Stricker BH, Sturkenboom MCJM. All-cause mortality associated with atypical
and typical antipsychotics in demented outpatients. Pharmacoepidemiology and drug safety 2007; 16(5): 538-544.
https://doi.org/10.1002/pds.1334
Unstructured Citation
[58] Raivio MM, Laurila JV, Strandberg TE, Tilvis RS, Pitkälä KH. Neither atypical nor conventional antipsychotics increase
mortality or hospital admissions among elderly patients with dementia: a two-year prospective study. The American journal
of geriatric psychiatry 2007; 15(5): 416-424.
https://doi.org/10.1097/JGP.0b013e31802d0b00
Unstructured Citation
[59] Nonino F, De Girolamo G, Gamberini L, Goldoni CA. Survival among elderly Italian patients with dementia treated with
atypical antipsychotics: observational study. Neurological sciences 2006; 27(6): 375–380.
https://doi.org/10.1007/s10072-006-0716-6
Unstructured Citation
[60] Suh G-H, Shah A. Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study
in a nursing home. International psychogeriatrics 2005; 17(3): 429-441.
https://doi.org/10.1017/S1041610205002243
Unstructured Citation
[61] Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, et al. The dementia antipsychotic withdrawal
trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. The Lancet. Neurology 2009; 8(2): 151-157.
https://doi.org/10.1016/S1474-4422(08)70295-3
Unstructured Citation
[62] De Deyn PP, Rabheru K, Rasmussen A, Bocksberger JP, Dautzenberg PL, Eriksson S, Lawlor BA. A randomized trial of risperidone,
placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999; 53(5): 946-955.
https://doi.org/10.1212/WNL.53.5.946
Unstructured Citation
[63] Fok MC, Sepehry AA, Frisch L, Sztramko R, Borger van der Burg BLS, Vochteloo AJH, Chan P. Do antipsychotics prevent postoperative
delirium? A systematic review and meta-analysis. International journal of geriatric psychiatry 2015; 30(4): 333-344.
https://doi.org/10.1002/gps.4240
Unstructured Citation
[64] Elie M, Boss K, Cole MG, McCusker J, Belzile E, Ciampi A. A retrospective, exploratory, secondary analysis of the association
between antipsychotic use and mortality in elderly patients with delirium. International psychogeriatrics 2009; 21(3): 588-592.
https://doi.org/10.1017/S1041610209008977
Unstructured Citation
[65] Wang W, Li H-L, Wang D-X, Zhu X, Li S-L, Yao G-Q, Chen K-S, et al. Haloperidol prophylaxis decreases delirium incidence
in elderly patients after noncardiac surgery: a randomized controlled trial. Critical care medicine 2012; 40(3): 731-739.
https://doi.org/10.1097/CCM.0b013e3182376e4f
Unstructured Citation
[66] Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J. 11-year follow-up of mortality in
patients with schizophrenia: a population-based cohort study (FIN11 study). The Lancet 2009; 374: 620-627.
https://doi.org/10.1016/S0140-6736(09)60742-X
Unstructured Citation
[67] Bhalerao S, Seyfried LS, Kim HM, Chiang C, Kavanagh J, Kales HC. Mortality risk with the use of atypical antipsychotics
in later-life bipolar disorder. Journal of geriatric psychiatry and neurology 2012; 25(1): 29-36.
https://doi.org/10.1177/0891988712436687
Unstructured Citation
[68] Gao K, Kemp DE, Ganocy SJ, Gajwani P, Xia G, Calabrese JR. Antipsychoticinduced extrapyramidal side effects in bipolar
disorder and schizophrenia: a systematic review. Journal of clinical psychopharmacology 2008; 28(2): 203-209.
https://doi.org/10.1097/JCP.0b013e318166c4d5
Unstructured Citation
[69] Azermai M. Dealing with behavioral and psychological symptoms of dementia: a general overview. Psychology Research and
Behavior Management 2015; 8: 181.
https://doi.org/10.2147/PRBM.S44775
Unstructured Citation
[70] Treloar A, Crugel M, Prasanna A, Solomons L, Fox C, Paton C, Katona C. Ethical dilemmas: should antipsychotics ever be
prescribed for people with dementia? The British journal of psychiatry 2010; 197(2): 88-90.
https://doi.org/10.1192/bjp.bp.109.076307
Unstructured Citation
[71] Saxena S, Lawley D. Delirium in the elderly: a clinical review. Postgraduate medical journal 2009; 85(1006): 405-413.
https://doi.org/10.1136/pgmj.2008.072025