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Farmacoterapia antipsicotica e disturbi cognitivi

  • P. ValsecchiEmail author
  • F. Bettini
  • E. Tamussi

Riassunto

Fra le dimensioni sintomatologiche della schizofrenia i deficit cognitivi si sono dimostrati il più valido indice prognostico del funzionamento a lungo termine (Green, 1996) e il loro impatto è risultato maggiore di quello di altri aspetti della malattia come, ad esempio, la gravità dei sintomi produttivi (Harvey et al., 1998). Nonostante queste evidenze, lo sviluppo di farmaci per il trattamento della schizofrenia si è per molto tempo concentrato per lo più sui sintomi positivi. L’introduzione degli antipsicotici di seconda generazione ha generato nuovo interesse anche perché questi farmaci, rispetto agli antipsicotici di prima generazione, promettono numerosi vantaggi fra cui proprio un possibile beneficio sulle funzioni cognitive. In una meta-analisi (Leucht et al., 2009) di confronto tra antipsicotici di prima e seconda generazione, amisulpride, clozapina, olanzapina e risperidone si sono dimostrati superiori in termini di efficacia globale e, considerando sintomi specifici, amisulpride, clozapina, olanzapina, risperidone e quetiapina sono risultati più efficaci sulla sintomatologia positiva, negativa e depressiva. Se la superiorità dei nuovi antipsicotici si confermasse anche in termini cognitivi avrebbe un enorme impatto sulla disabilità associata alla schizofrenia. Il miglioramento dei sintomi cognitivi rappresenta, pertanto, il nuovo target nel trattamento dei pazienti affetti da schizofrenia.

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Bibliografia

  1. Ahn YM, Lee KY, Kim CE et al (2009) Changes in neurocognitive function in patients with schizophrenia after starting or switching to amisulpride in comparison with the normal controls. J Clin Psychopharmacol 29:117–123PubMedCrossRefGoogle Scholar
  2. Benwell ME, Balfour DJ, Birrell CE (1995) Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine. Br J Pharmacol 114:454–460PubMedCrossRefGoogle Scholar
  3. Buchanan RW, Holstein C, Breier A (1994) The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance. Biol Psychiatry 36:717–725PubMedCrossRefGoogle Scholar
  4. Cassens G, Inglis AK, Appelbaum PS et al (1990) Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull 16:477–499PubMedCrossRefGoogle Scholar
  5. Castner SA, Williams GV, Goldman-Rakic PS (2000) Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science 287:2020–2022PubMedCrossRefGoogle Scholar
  6. Davidson M, Galderisi S, Weiser M et al (2009) Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry 166:675–82PubMedCrossRefGoogle Scholar
  7. Friedman JI (2004) Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonists. Psychopharmacology (Berl) 174:45–53CrossRefGoogle Scholar
  8. Friedman JI, Temporini H, Davis KL (1999) Pharmacologic strategies for augmenting cognitive performance in schizophrenia. Biol Psychiatry 45:1–16PubMedCrossRefGoogle Scholar
  9. Gibel A, Ritsner MS (2008) Neurocognitive effects of ziprasidone and related factors in patients with chronic schizophrenia undergoing usual care: a 12-month, open-label, flexible-dose, naturalistic observational trial. Clin Neuropharmacol 31:204–220PubMedCrossRefGoogle Scholar
  10. Grace J, Bellus SB, Raulin ML, et al (1996) Long-term impact of clozapine and psychosocial treatment on psychiatric symptoms and cognitive functioning. Psychiatr Serv 47:41–45PubMedGoogle Scholar
  11. Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 153:321–330PubMedGoogle Scholar
  12. Gurpegui M, Alvarez E, Bousono M et al (2007) Effect of olanzapine or risperidone treatment on some cognitive functions in a one-year follow-up of schizophrenia outpatients with prominent negative symptoms. Eur Neuropsychopharmacol 17:725–734PubMedCrossRefGoogle Scholar
  13. Harvey PD, Bowie CR, Loebel A (2006) Neuropsychological normalization with long-term atypical antipsychotic treatment: results of a six-month randomized, double-blind comparison of ziprasidone vs. olanzapine. J Neuropsychiatry Clin Neurosci 18:54–63PubMedCrossRefGoogle Scholar
  14. Harvey PD, Howanitz E, Parrella M et al (1998) Symptoms, cognitive functioning, and adaptive skills in geriatric patients with lifelong schizophrenia: a comparison across treatment sites. Am J Psychiatry 155:1080–1086PubMedGoogle Scholar
  15. Harvey PD, Meltzer H, Simpson GM et al (2004b) Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia. Schizophr Res 66:101–113PubMedCrossRefGoogle Scholar
  16. Harvey PD, Siu CO, Romano S (2004a) Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Psychopharmacology 172:324–332PubMedCrossRefGoogle Scholar
  17. Hill SK, Bishop JR, Palumbo D et al (2010) Effect of second-generation antipsychotics on cognition: current issues and future challenges. Expert Rev Neurother 10:43–57PubMedCrossRefGoogle Scholar
  18. Houthoofd SA, Morrens M, Sabbe BG (2008) Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder. Clin Ther 30:1565–1589PubMedCrossRefGoogle Scholar
  19. Javitt DC (2006) Is the glycine site half saturated or half unsaturated? Effects of glutamatergic drugs in schizophrenia patients. Curr Opin Psychiatry 19:151–157PubMedCrossRefGoogle Scholar
  20. Kapur S, Zipursky R, Jones C et al (2000) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514–520PubMedCrossRefGoogle Scholar
  21. Keefe RS, Sweeney JA, Gu H et al (2007a) Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, doubleblind 52-week comparison. Am J Psychiatry 164:1061–1071PubMedCrossRefGoogle Scholar
  22. Keefe RS, Bilder RM, Davis SM et al (2007b) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:633–647PubMedCrossRefGoogle Scholar
  23. Keefe RS, Silva SG, Perkins DO et al (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222PubMedCrossRefGoogle Scholar
  24. Kern RS, Green MF, Cornblatt BA et al (2006) The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology (Berl) 187:312–320CrossRefGoogle Scholar
  25. Kim SW, Shin IS, Kim JM et al (2009) Effects of switching to long-acting injectable risperidone from oral atypical antipsychotics on cognitive function in patients with schizophrenia. Hum Psychopharmacol 24:565–573PubMedCrossRefGoogle Scholar
  26. Kivircik Akdede BB, Alptekin K, Kitiş A et al (2005) Effects of quetiapine on cognitive functions in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29:233–238PubMedCrossRefGoogle Scholar
  27. Knable MB, Weinberger DR (1997) Dopamine, the prefrontal cortex and schizophrenia. J Psychopharmacol (Oxf) 11:123–131CrossRefGoogle Scholar
  28. Lee MA, Jayathilake K, Meltzer HY (1999) A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizophr Res 37:1–11PubMedCrossRefGoogle Scholar
  29. Leucht S, Corves C, Arbter D et al (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373:31–41PubMedCrossRefGoogle Scholar
  30. Li Z, Huang M, Ichikawa J et al (2005) N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors. Neuropsychopharmacology 30:1986–95PubMedCrossRefGoogle Scholar
  31. Lieberman JA, Stroup TS, McEvoy JP et al (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223PubMedCrossRefGoogle Scholar
  32. Malhotra AK, Burdick KE, Razi K, et al (2006) Ziprasidone-induced cognitive enhancement in schizophrenia: Specificity or pseudospecificity? Schizophr Res 87:181–184PubMedCrossRefGoogle Scholar
  33. Minzenberg MJ, Carter CS (2012) Developing treatments for impaired cognition in schizophrenia. Trends Cogn Sci 16:35–42PubMedCrossRefGoogle Scholar
  34. Olincy A, Harris JG, Johnson LL et al (2006) Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 63:630–638PubMedCrossRefGoogle Scholar
  35. Purdon SE, Labelle A, Boulay L (2001a) Neuropsychological change in schizophrenia after 6 weeks of clozapine. Schizophr Res 48:57–67PubMedCrossRefGoogle Scholar
  36. Purdon SE, Malla A, Labelle A et al (2001b) Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. J Psychiatry Neurosci 26:137–149PubMedGoogle Scholar
  37. Raedler TJ, Bymaster FP, Tandon R et al (2007) Towards a muscarinic hypothesis of schizophrenia. Mol Psychiatry 12:232–246PubMedGoogle Scholar
  38. Ramaekers JG, Louwerens JW, Muntjewerff ND et al (1999) Psychomotor, cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic. J Clin Psychopharmacol 19:209–221PubMedCrossRefGoogle Scholar
  39. Riedel M, Schennach-Wolff R, Musil R et al (2010) Neurocognition and its influencing factors in the treatment of schizophrenia-effects of aripiprazole, olanzapine, quetiapine and risperidone. Hum Psychopharmacol 25:116–125PubMedCrossRefGoogle Scholar
  40. Roth BL, Hanizavareh SM, Blum AE (2004) Serotonin receptors represent highly favourable molecular targets for cognitive enhancement in schizophrenia and other disorders. J Psychopharmacol (Oxf) 174:17–24Google Scholar
  41. Saeedi H, Remington G, Christensen BK (2006) Impact of haloperidol, a dopamine antagonist, on cognition and mood. Schizophr Res 85:222–231PubMedCrossRefGoogle Scholar
  42. Sax KW, Strakowski SM, Keck PE Jr (1998) Attentional improvement following quetiapine fumarate treatment in schizophrenia. Schizophr Res 1998 33:151–155PubMedCrossRefGoogle Scholar
  43. Sharma T, Antonova L (2003) Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am 26:25–40PubMedCrossRefGoogle Scholar
  44. Singh J, Kour K, Jayaram MB (2012) Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database Syst Rev 18:1Google Scholar
  45. Strauss ME, Reynolds KA, Jayaram G et al (1990) Effects of anticholinergic medication on memory in schizophrenia. Schizophr Res 3:127–129PubMedCrossRefGoogle Scholar
  46. Swartz MS, Perkins DO, Stroup TS et al (2007) Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry 164:428–436PubMedCrossRefGoogle Scholar
  47. Sweeney JA, Haas GL, Keilp JG et al (1991) Evaluation of the stability of neuropsychological functioning after acute episodes of schizophrenia: oneyear followup study. Psychiatry Res 38:63–76PubMedCrossRefGoogle Scholar
  48. Tsai G, Lane HY, Yang P et al (2004) Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia.Biol Psychiatry 55:452–456PubMedCrossRefGoogle Scholar
  49. Tyson PJ, Laws KR, Flowers KA et al (2006) Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics. Psychiatry Clin Neurosci 60:473–479PubMedCrossRefGoogle Scholar
  50. Velligan DI, Newcomer J, Pultz J et al (2002) Does cognitive function improve with quetiapine in comparison to haloperidol? Schizophr Res 53:239–248PubMedCrossRefGoogle Scholar
  51. Woodward ND, Purdon SE, Meltzer HY et al (2008) A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia.Int J Neuropsychopharmacol 8:457–472CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  1. 1.Dipartimento di Scienze Cliniche e SperimentaliUniversità di BresciaItaly
  2. 2.Unità Operativa di Psichiatria 22, Dipartimento di Salute MentaleAzienda Ospedaliera Spedali Civili di BresciaItaly

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