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Rischio di mortalità con i farmaci antipsicotici nella popolazione psichiatrica anziana? Una revisione sistematica della letteratura
Titolo Rivista: RIVISTA SPERIMENTALE DI FRENIATRIA 
Autori/Curatori: Riccardo De Giorgi, Andrea Cipriani 
Anno di pubblicazione:  2016 Fascicolo: Lingua: Italiano 
Numero pagine:  24 P. 127-150 Dimensione file:  225 KB
DOI:  10.3280/RSF2016-002008
Il DOI è il codice a barre della proprietà intellettuale: per saperne di più:  clicca qui   qui 


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.


Keywords: Antipsicotici, mortalità, anziani, psicogeriatria, revisione sistematica.

  1. [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
  2. [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.
  3. [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.
  4. [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.
  5. [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.
  6. [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.
  7. [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.
  8. [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.
  9. [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.
  10. [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.
  11. [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.
  12. [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.
  13. [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.
  14. [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.
  15. [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.
  16. [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.
  17. [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
  18. [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.
  19. [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.
  20. [21] Ownby RL. Clinical trials in geriatric disorders. Current psychiatry reports 2001; 3(1): 11-12.
  21. [22] Gardner DM, Baldessarini RJ, Waraich P. Modern antipsychotic drugs: a critical overview. CMAJ 2005; 172(13): 1703-1711.
  22. [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.
  23. [25] Jin H, Meyer JM, Jeste DV. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophrenia research 2004; 71(2-3): 195-212.
  24. [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.
  25. [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.
  26. [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
  27. [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.
  28. [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
  29. [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.
  30. [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.
  31. [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.
  32. [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
  33. [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.
  34. [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.
  35. [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.
  36. [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.
  37. [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.
  38. [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.
  39. [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.
  40. [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.
  41. [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.
  42. [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.
  43. [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.
  44. [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.
  45. [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.
  46. [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.
  47. [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.
  48. [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.
  49. [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.
  50. [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.
  51. [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.
  52. [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.
  53. [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.
  54. [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.
  55. [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.
  56. [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.
  57. [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.
  58. [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.
  59. [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.
  60. [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.
  61. [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.
  62. [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.
  63. [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.
  64. [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.
  65. [69] Azermai M. Dealing with behavioral and psychological symptoms of dementia: a general overview. Psychology Research and Behavior Management 2015; 8: 181.
  66. [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.
  67. [71] Saxena S, Lawley D. Delirium in the elderly: a clinical review. Postgraduate medical journal 2009; 85(1006): 405-413.

Riccardo De Giorgi, Andrea Cipriani, in "RIVISTA SPERIMENTALE DI FRENIATRIA" 2/2016, pp. 127-150, DOI:10.3280/RSF2016-002008

   

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