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Obiettivi e strategie dell’assistenza riabilitativa multidisciplinare al paziente oncologico

Obiettivi e strategie dell’assistenza riabilitativa multidisciplinare al paziente oncologico Roma , 19 settembre 2006. Opzioni farmacologiche nel trattamento della depressione.

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Obiettivi e strategie dell’assistenza riabilitativa multidisciplinare al paziente oncologico

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  1. Obiettivi e strategie dell’assistenza riabilitativa multidisciplinare al paziente oncologico Roma , 19 settembre 2006 Opzioni farmacologiche nel trattamento della depressione Riccardo Torta SCDU Psicologia Clinica e Oncologica Dipartimenti di Oncologia e Neuroscienze ASO San Giovanni Battista ed Università di Torino

  2. Pathogenesis of depression : biopsychosocial hypothesis Mind Cultural factors Psychological factors Body World Environmental factors Physiological and physiopathological factors Brain

  3. Increase of mortality rate in patients with somatic diseases and mood depression range of increase of mortality • Hypertension • Stroke • Diabetes • Cardiovasc. dis. • Cancer 2,27 x DD 3,00 x DD 3,84 x DD 4,04 x DD 4,46 x DD Black & Markides,1999

  4. Depression • smoking • therapeutic compliance diet physical activity Behavioural factors • obesity • hyperglycemia • dyslipidemia • hypertension HPA hyperactivity ? Immunological alterations • cellular immunity • reduction Reduced HRV • arrythmias PLT’s hyperaggregation ADs? Mortality increase Joynt et al, Biol Psychiatry, 54, 2003

  5. Brain stem sleep,nausea, vomit SEROTONERGIC PATHWAYS Basal Ganglia Akatisia/agitationcompulsions rostral raphe nuclei Neocortex mood Hyppocampus Limbic areas caudal raphe nuclei mood anxiety panic Hypothalamus sexual and eating behaviour Vessels Gut Medulla vasoconstriction vasodilatation orgasm pain motility

  6. anxiety pain 5HT and NE dysregulation depression chronic stress Stahl, 2002; Torta e Lacerenza, 2002; Leo, 2003

  7. SSRI NSRI NRI MAOI Stress hormons and Antidepressants Treatment with antidepressants Clinical improvement < CRH and AVP concentrations 1 > GR s gene expression 2 > corticosteroid brain binding 2 Normalization of HPA axis activity 1- De Bellis et al, 1999 2- Reul et al.,1993

  8. neurotrasnmitters release receptors down regulation Receptor regulation of transductional mechanisms effector Protein kinase Control of genic expression (neurotrophic hypothesis) BDNF NGF nucleus Effects of antidepressants after chronic administration

  9. cisplatin vincristine taxans neuronal store of metal microtubular alterations neuronal damage Anti-cancer chemotherapy and neurotoxicity NGF Nerve Growth Factor ? antidepressants neurotoxicity prophylaxis Hayakawa et al., 1998

  10. - anti-inflammatory cytokines + - ADs Physiological Factors pro-inflammatory cytokines NO/PGE2 CRH activation HPA hyperactivity IDO induction IFNa tryptophan depletion reduced 5HT availability neurotransmitters modifications depressive symptoms

  11. Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram Escitalopram SSRIs NARIs Reboxetine 5HT and NE dysregulation Mirtazapine TCAs NaSSAs Amitritptyline Clomipramine SNRIs Venlafaxine Duloxetine

  12. La scelta dello psicofarmaco: la priorità della tollerabilità aspetti clinici paziente aspetti dinamici e cinetici farmaco

  13. Antidepressivi in oncologia TCA az.antalgica az. anticolinergica Mianserina az.antalgica leucopenia, sedazione Trazodone az. antalgica ipotensione SSRI az.antalgica collat. GE, iporessia NSRI az. antalgica collat. GE NaSSA az.antinausea astenia, sedazione NARI az. socializzante attivazione, ritenzione Benzam.sost. az.cenestesica incremento PRL SAMe trofismo mucose ev > os es. vantaggi es. limiti

  14. Antidepressivi in oncologia TCA az.antalgica az. anticolinergica Trazodone az. antalgica ipotensione SSRI az.antalgica collat. GE, iporessia NSRI az. antalgica collat. GE, attivazione NaSSA az.antinausea astenia, sedazione NARI az. socializzante attivazione, ritenzione Benzam.sost. az.cenestesica incremento PRL SAMe trofismo mucose ev > os es. vantaggi es. limiti

  15. Antidepressivi e dolore

  16. gate control dolore Mondo 2 : eventi emotivi e cognitivi Mondo 1 : eventi fisici filtro mentale nocicezione Tiengo,1992; mod. dolore

  17. variabilità interindividuale nella percezione del dolore (Coghill et al., 2003) (Coghill et al., 2003) alta sensibilità : > attivazione cingolo anteriore e cortex somato-sensoriale

  18. Effects of antidepressants after acute and chronic administration • first antalgic effect can be indipendent from antidepressantactivity • firstantalgic effect is reached with low doses • first antalgic effect demonstrates a rapid onset reuptake inhibition down regulation Receptor - later antalgic effect is also related to mood improvement

  19. Coping Dolore QUID Mini-MAC

  20. Levine e Gordon naloxone neurobiologia dell’analgesia da placebo blocco effetto placebo Nature,1984 Pain,1998 Pain,1997 Benedetti et al. Benedetti et al. effetti collaterali di depressione respiratoria blocco recettori CCK potenziamento analgesia da placebo Effetto non farmacologico di un farmaco

  21. “ La parola è un gran dominatore... riesce infatti a calmare la paura, ad eliminare il dolore... C’è, tra la potenza della parola e la funzione dell’anima lo stesso rapporto che tra l’azione dei farmaci e le funzioni del corpo” Gorgia di Leontini (Elogio di Elena)

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