1 / 35

ANTIPSICOTICI ED EVENTI AVVERSI CEREBROVASCOLARI

Università degli Studi di Messina Dipartimento Clinico e Sperimentale di Medicina e Farmacologia Sezione di Farmacologia. ANTIPSICOTICI ED EVENTI AVVERSI CEREBROVASCOLARI. Edoardo Spina. Disturbi psichici e comportamentali della demenza (BPSD). Agitazione. Aggressività. Affaccendamento

serge
Download Presentation

ANTIPSICOTICI ED EVENTI AVVERSI CEREBROVASCOLARI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Università degli Studi di Messina Dipartimento Clinico e Sperimentale di Medicina e Farmacologia Sezione di Farmacologia ANTIPSICOTICI ED EVENTI AVVERSI CEREBROVASCOLARI Edoardo Spina

  2. Disturbi psichici e comportamentali della demenza (BPSD) Agitazione Aggressività Affaccendamento Vagabondaggio Pedinamento, Irrequietezza, Grida Disinibizione, Stereotipie, Vestirsi/svestirsi Disturbi del sonno Resistenza aggressiva Aggressività fisica Aggressività verbale Apatia Ritiro Mancanza di interessi Demotivazione Tristezza Pianto Disperazione Bassa autostima Ansia Colpa Allucinazioni Deliri Falsi riconoscimenti Depressione Psicosi

  3. Cochrane Database Syst Rev, 2002;(2):CD002852 Haloperidol for agitation in dementia Lonergan et al. …Evidence suggests that haloperidol was useful in the control of aggression, but was associated with increased side effects; there was no evidence to support the routine use of this drug for other manifestations of agitated dementia…

  4. Drugs Aging 19: 257-276, 2002 Pharmacological treatment of psychosis and agitation in elderly patients with dementia: four decades of experience Kindermann et al. …Conventional antipsychotics are modestly effective for the treatment of psychosis and agitation in elderly individuals with dementia, whereas newer treatments such as atypical antipsychotics appear to be at least as effective while having fewer adverse effects…

  5. Alexopoulos et al, J Clin Psych, 2004; 65 (suppl 2) • Trattamento dei pazienti affetti da demenza associata ad agitazione e deliri • Risperidone (0.5-2 mg/day) • Olanzapina (5-7.5 mg/day) • Quetiapina (50-150 mg/day)

  6. N: 1570 Istituzionalizzati: 96% M. Alzheimer: 76.3% BMJ 2004; 329: 75

  7. Antipsicotici ed eventi avversi cerebrovascolari La nascita del problema

  8. 2003 Safety Alert - RISPERDAL (risperidone) 16-April-2003 Dear Healthcare Provider, Janssen Pharmaceutica Products, L.P., would like to inform you of important changes regarding RISPERDAL (risperidone). The RISPERDAL prescribing information has been updated with the addition of the following information: WARNINGS Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73-97) in trials of risperidone in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with risperidone compared to patients treated with placebo. RISPERDAL has not been shown to be safe or effective in the treatment of patients with dementia-related psychosis. This update is based on data from 4 placebo-controlled trials conducted in elderly patients with dementia (N=1230). Additional information on these and other clinical trials conducted in elderly patients can be obtained by calling 1-800-JANSSEN (800-526-7736). We remind you that, like all other antipsychotics, RISPERDAL is not indicated for the treatment of dementia.

  9. “There are insufficient data to confirm any difference in the risk of mortality or cerebrovascular accidents among atypical neuroleptics, including olanzapine, or between atypical and conventional neuroleptics”

  10. Incidenza di eventi avversi cerebrovascolari in pazienti anziani affetti da demenza negli studi clinici controllati con placebo relativi a risperidone Wooltorton, 2002

  11. Incidenza di eventi avversi cerebrovascolari in pazienti anziani affetti da demenza negli studi clinici controllati con placebo relativi ad olanzapina Wooltorton, 2004

  12. Fattori di rischio per CVAE ed eventi fatali • Età > 80 anni • Pregresso TIA • Ipertensione • Fumo • Diabete • Fibrillazione atriale • Malnutrizione, disidratazione, patologie polmonari • Sedazione e concomitante uso di benzodiazepine • Demenza vascolare

  13. Antipsicotici ed eventi avversi cerebrovascolariProblematiche • Antipsicotici tradizionali vs. atipici? • Pazienti non affetti da demenza, anziani e non?

  14. Antipsicotici ed eventi avversi cerebrovascolari Studi epidemiologici

  15. Nessuna differenza statisticamente significativa nell’insorgenza di CVAE • in 11.400 pazienti anziani trattati con olanzapina, risperidone e tipici (risk ratio di 1.1 per olanzapina e di 1.4 per risperidone)

  16. Studio retrospettivo di coorte, 6 anni, su oltre 32.000 pazienti anziani con demenza RR per stroke ischemico di AP atipici rispetto a tradizionali: 1.01 (IC 95%: 0.81-1.26) BMJ 2005; 330: 445

  17. Barnett et al. Comparison of risk of cerebrovascular events in an elderly VA population with dementia between antipsychotic and nonantipsychotic users J Clin Psychopharmacol 19: 257-276, 2007 Rischio di ospedalizzazione per evento cerebrovascolare All patients (n = 14.029) No antipsychotic use 1 FGA 1.29 SGA 1.20 Alzheimer dementia pts (n = 10.304) No antipsychotic use 1 FGA 0.96 SGA 1.10 Vascular dementia pts (n = 3.725) No antipsychotic use 1 FGA 2.57 SGA 1.47

  18. Sacchetti E, Trifirò G, Caputi AP, Turrina C, Spina E, Cricelli C, Brignoli O, Sessa E, Mazzaglia G

  19. Antipsicotici ed eventi avversi cerebrovascolari Ipotesi patogenetiche

  20. Antipsicotici ed eventi avversi cerebrovascolari Meccanismi patogenetici ipotizzabili: • Ipotensione ortostatica • Dislipidemia  aterosclerosi • Diabete  aterosclerosi • Iperprolattinemia  aterosclerosi • Eccessiva sedazione  disidratazione • Tromboembolismo venoso Smith and Beier, 2004; Jeste et al., 2008

  21. Antipsicotici e mortalità da tutte le cause

  22. FDA, 11 aprile 2005

  23. Schneider et al., JAMA 2005; 294: 1934-1943

  24. Wang et al., 2005

  25. Wang et al., 2005

  26. 2007; 146: 775-786

  27. Antipsicotici e mortalità Possibili meccanismi: • Alterazioni metaboliche • Turbe della conduzione cardiaca • Eccessiva sedazione  aspirazione  infezioni respiratorie Jeste et al., 2008

  28. Evidence suggest that risperidone and olanzapine are useful in reducing aggression in people with dementia and risperidone also reduces psychosis. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients unless there is marked risk or severe distress

  29. Conclusions Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer’s disease

  30. Grazie per l’attenzione!

More Related