CNS Drugs

, Volume 24, Issue 1, pp 9–20 | Cite as

Progress in Defining Optimal Treatment Outcome in Schizophrenia

Leading Article


Historically, schizophrenia has been associated with early-onset, persistent symptoms, and progressive decline accompanied by poor functional recovery. The advent of effective drugs in the 1950s improved symptom control, at least from the standpoint of positive features (e.g. hallucinations, delusions). However, even here the response was limited and efficacy in other symptom domains (cognitive, deficit/negative) was minimal. With clozapine as the prototype, the second-generation antipsychotics arrived in the 1990s with claims of improved tolerability, as well as greater and broader clinical efficacy, all of which was to translate to gains in functional outcome and quality of life. The capacity of these drugs to effect such changes has since been tempered, but it remains that the research and hope generated served as an impetus to redefine outcomes.

A medical-based model, centred on pharmacotherapy and symptom resolution, has given way to a re-conceptualization of schizophrenia and treatment goals. There is a clearer distinction between clinical and functional outcomes, and, with this, greater attention has been given to these other symptom domains that curtail improvement in the latter. At the same time, a concerted shift to shared decision making has underscored quality-of-life issues that benefit from, but cannot be guaranteed by, either clinical or functional improvement. To this end, the field has now embraced a recovery model that is seen as a process, multidimensional and individualized, rather than dichotomous and symptom driven.


  1. 1.
    Kraepelin E. Dementia praecox and paraphrenia. Melbourne (VIC): Krieger Publishing Co, 1971Google Scholar
  2. 2.
    Bleuler E. Dementia praecox or the group of schizophrenias. New York: International Universities Press, 1950Google Scholar
  3. 3.
    Lopez-Munoz F, Alamo C, Cuenca E, et al. History of the discovery and clinical introduction of chlorpromazine. Ann Clin Psychiatry 2005; 17: 113–35PubMedGoogle Scholar
  4. 4.
    Kirkby KC. Social context and health consequences of the antipsychotics introduction. Ann Clin Psychiatry 2005; 17: 141–6PubMedGoogle Scholar
  5. 5.
    Andreasen NC, Olsen S. Negative v positive schizophrenia: definition and validation. Arch Gen Psychiatry 1982; 39: 789–94PubMedGoogle Scholar
  6. 6.
    Crow TJ. Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 1980; 137: 383–6PubMedGoogle Scholar
  7. 7.
    Carpenter Jr WT, Heinrichs DW, Wagman AM. Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry 1988; 145: 578–83PubMedGoogle Scholar
  8. 8.
    Hippius H. A historical perspective of clozapine. J Clin Psychiatry 1999; 60Suppl. 12: 22–3PubMedGoogle Scholar
  9. 9.
    Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988 Sep; 45(9): 789–96PubMedGoogle Scholar
  10. 10.
    Fleischhacker W. ‘Atypical antipsychotics’ and the semantics of psychopharmacology. Curr Opin Psychiatry 2002; 15: 1–2Google Scholar
  11. 11.
    Remington G, Kapur S. Atypical antipsychotics: are some more atypical than others? Psychopharmacology (Berl) 2000; 148(1): 3–15Google Scholar
  12. 12.
    Kapur S, Remington G. Dopamine D2 receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biol Psychiatry 2001; 50(11): 873–83PubMedGoogle Scholar
  13. 13.
    Remington G. Understanding antipsychotic ‘atypicality’: a clinical and pharmacological moving target. J Psychiatry Neurosci 2003; 28(4): 275–84PubMedGoogle Scholar
  14. 14.
    Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63(10): 1079–87PubMedGoogle Scholar
  15. 15.
    Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371(9618): 1085–97PubMedGoogle Scholar
  16. 16.
    Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353(12): 1209–23PubMedGoogle Scholar
  17. 17.
    Elkis H. Treatment-resistant schizophrenia. Psychiatr Clin North Am 2007; 30(3): 511–33PubMedGoogle Scholar
  18. 18.
    Lewis SW, Barnes TR, Davies L, et al. Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull 2006; 32(4): 715–23PubMedGoogle Scholar
  19. 19.
    McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006; 163(4): 600–10PubMedGoogle Scholar
  20. 20.
    Buckley PF, Stahl SM. Pharmacological treatment of negative symptoms of schizophrenia: therapeutic opportunity or cul-de-sac? Acta Psychiatr Scand 2007; 115(2): 93–100PubMedGoogle Scholar
  21. 21.
    Emsley R, Oosthuizen P. Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 2004; 7(2): 219–38PubMedGoogle Scholar
  22. 22.
    Marder SR. Drug initiatives to improve cognitive function. J Clin Psychiatry 2006; 67Suppl. 9: 31–5PubMedGoogle Scholar
  23. 23.
    Geddes J, Freemantle N, Harrison P, et al. Atypical anti-psychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ 2000; 321(7273): 1371–6PubMedGoogle Scholar
  24. 24.
    Leucht S, Pitschel-Walz G, Abraham D, et al. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo: a meta-analysis of randomized controlled trials. Schizophr Res 1999; 35(1): 51–68PubMedGoogle Scholar
  25. 25.
    Miller DD, Caroff SN, Davis SM, et al. Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry 2008; 193(4): 279–88PubMedGoogle Scholar
  26. 26.
    Weiden PJ. EPS profiles: the atypical antipsychotics are not all the same. J Psychiatr Pract 2007; 13(1): 13–24PubMedGoogle Scholar
  27. 27.
    Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry 2008; 21(2): 151–6PubMedGoogle Scholar
  28. 28.
    Kane JM. Tardive dyskinesia circa 2006. Am J Psychiatry 2006; 163(8): 1316–8PubMedGoogle Scholar
  29. 29.
    Voruganti LP, Baker LK, Awad AG. New generation anti-psychotic drugs and compliance behaviour. Curr Opin Psychiatry 2008; 21(2): 133–9PubMedGoogle Scholar
  30. 30.
    Agid O, Kapur S, Remington G. Emerging drugs for schizophrenia. Expert Opin Emerg Drugs 2008; 13(3): 479–95PubMedGoogle Scholar
  31. 31.
    Brewer WJ, Wood SJ, Phillips LJ, et al. Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. Schizophr Bull 2006; 32(3): 538–55PubMedGoogle Scholar
  32. 32.
    Fenton WS, McGlashan TH. Antecedents, symptom progression, and long-term outcome of the deficit syndrome in schizophrenia. Am J Psychiatry 1994; 151(3): 351–6PubMedGoogle Scholar
  33. 33.
    Hoff AL, Sakuma M, Wieneke M, et al. Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia. Am J Psychiatry 1999; 156(9): 1336–41PubMedGoogle Scholar
  34. 34.
    Kelley ME, Gilbertson M, Mouton A, et al. Deterioration in premorbid functioning in schizophrenia: a developmental model of negative symptoms in drug-free patients. Am J Psychiatry 1992; 149(11): 1543–8PubMedGoogle Scholar
  35. 35.
    Yung AR, McGorry PD. The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophr Bull 1996; 22(2): 353–70PubMedGoogle Scholar
  36. 36.
    Stahl SM, Buckley PF. Negative symptoms of schizophrenia: a problem that will not go away. Acta Psychiatr Scand 2007; 115(1): 4–11PubMedGoogle Scholar
  37. 37.
    Guy W, editor. Assessment manual for psychopharmacology. Rockville (MD): National Institute of Mental Health, 1976Google Scholar
  38. 38.
    Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799–812Google Scholar
  39. 39.
    Spitzer RL, Endicott J. Schedule for affective disorders and schizophrenia-change version. 3rd ed. New York: New York State Psychiatric Institute, Biometrics Research, 1978Google Scholar
  40. 40.
    Leucht S, Engel RR. The relative sensitivity of the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale in antipsychotic drug trials. Neuropsychopharmacology 2006; 31: 406–12PubMedGoogle Scholar
  41. 41.
    Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13(2): 261–76PubMedGoogle Scholar
  42. 42.
    Andreasen NC. The Scale for the Assessment of Negative Symptoms (SANS). Iowa City (IA): University of Iowa, 1983Google Scholar
  43. 43.
    Andreasen NC. The Scale for the Assessment of Positive Symptoms (SAPS). Iowa City (IA): University of Iowa, 1984Google Scholar
  44. 44.
    Kirkpatrick B, Buchanan RW, McKenney PD, et al. The schedule for the deficit syndrome: an instrument for research in schizophrenia. Psychiatry Res 1989; 30(2): 119–23PubMedGoogle Scholar
  45. 45.
    Foussias G, Remington G. Negative symptoms in schizophrenia: avolition and Occam’s razor. Schizophr Bull. Epub 2008 Jul 21Google Scholar
  46. 46.
    Blanchard JJ, Horan WP, Collins LM. Examining the latent structure of negative symptoms: is there a distinct subtype of negative symptom schizophrenia? Schizophr Res 2005; 77(2–3): 151–65PubMedGoogle Scholar
  47. 47.
    Greenwood KE, Landau S, Wykes T. Negative symptoms and specific cognitive impairments as combined targets for improved functional outcome within cognitive remediation therapy. Schizophr Bull 2005; 31(4): 910–21PubMedGoogle Scholar
  48. 48.
    Ho BC, Nopoulos P, Flaum M, et al. Two-year outcome in first-episode schizophrenia: predictive value of symptoms for quality of life. Am J Psychiatry 1998; 155(9): 1196–201PubMedGoogle Scholar
  49. 49.
    Milev P, Ho BC, Arndt S, et al. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry 2005; 162(3): 495–506PubMedGoogle Scholar
  50. 50.
    Rosenheck R, Leslie D, Keefe R, et al. Barriers to employment for people with schizophrenia. Am J Psychiatry 2006; 163(3): 411–7PubMedGoogle Scholar
  51. 51.
    Kirkpatrick B, Fenton WS, Carpenter Jr WT, et al. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 2006; 32(2): 214–9PubMedGoogle Scholar
  52. 52.
    Emsley R, Rabinowitz J, Torreman M. The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophr Res 2003; 61(1): 47–57PubMedGoogle Scholar
  53. 53.
    Harvey PD, Green MF, Keefe RS, et al. Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry 2004; 65(3): 361–72PubMedGoogle Scholar
  54. 54.
    Kremen WS, Seidman LJ, Faraone SV, et al. The paradox of normal neuropsychological function in schizophrenia. J Abnorm Psychol 2000; 109(4): 743–52PubMedGoogle Scholar
  55. 55.
    Palmer BW, Heaton RK, Paulsen JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 1997; 11(3): 437–46PubMedGoogle Scholar
  56. 56.
    Murray RM, Lappin J, Di Forti M. Schizophrenia: from developmental deviance to dopamine dysregulation. Eur Neuropsychopharmacol 2008; 18Suppl. 3: S129–34PubMedGoogle Scholar
  57. 57.
    Ostrom TM. The sovereignty of social cognition. In: Wyer RS, Srull TK, editors. Handbook of social cognition. Hillsdale (NJ): Erlbaum, 1984: 1–37Google Scholar
  58. 58.
    Bertrand MC, Sutton H, Achim AM, et al. Social cognitive impairments in first episode psychosis. Schizophr Res 2007; 95(1–3): 124–33PubMedGoogle Scholar
  59. 59.
    Brekke JS, Hoe M, Long J, et al. How neurocognition and social cognition influence functional change during community-based psychosocial rehabilitation for individuals with schizophrenia. Schizophr Bull 2007; 33(5): 1247–56PubMedGoogle Scholar
  60. 60.
    Pijnenborg GH, Withaar FK, Evans JJ, et al. The predictive value of measures of social cognition for community functioning in schizophrenia: implications for neuropsychological assessment. J Int Neuropsychol Soc 2009; 15(2): 239–47PubMedGoogle Scholar
  61. 61.
    Meyer MB, Kurtz MM. Elementary neurocognitive function, facial affect recognition and social-skills in schizophrenia. Schizophr Res 2009; 110(1–3): 173–9PubMedGoogle Scholar
  62. 62.
    Corcoran R, Mercer G, Frith CD. Schizophrenia, symptomatology and social inference: investigating ‘theory of mind’ in people with schizophrenia. Schizophr Res 1995; 17(1): 5–13PubMedGoogle Scholar
  63. 63.
    Sergi MJ, Green MF, Widmark C, et al. Social cognition and neurocognition: effects of risperidone, olanzapine, and haloperidol. Am J Psychiatry 2007; 164(10): 1585–92PubMedGoogle Scholar
  64. 64.
    Green MF, Nuechterlein KH. The MATRICS initiative: developing a consensus cognitive battery for clinical trials. Schizophr Res 2004; 72(1): 1–3PubMedGoogle Scholar
  65. 65.
    Marder SR, Fenton W. Measurement and treatment research to improve cognition in schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res 2004; 72(1): 5–9PubMedGoogle Scholar
  66. 66.
    Buckley PF, Miller BJ, Lehrer DS, et al. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35(2): 383–402PubMedGoogle Scholar
  67. 67.
    Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res 1990; 3(4): 247–51PubMedGoogle Scholar
  68. 68.
    Collins AA, Remington G, Coulter K, et al. Depression in schizophrenia: a comparison of three measures. Schizophr Res 1996; 20(1–2): 205–9PubMedGoogle Scholar
  69. 69.
    Bassett AS, Bury A, Honer WG. Testing Liddle’s three-syndrome model in families with schizophrenia. Schizophr Res 1994; 12(3): 213–21PubMedGoogle Scholar
  70. 70.
    Dollfus S, Everitt B, Ribeyre JM, et al. Identifying subtypes of schizophrenia by cluster analyses. Schizophr Bull 1996; 22(3): 545–55PubMedGoogle Scholar
  71. 71.
    van der Gaag M, Cuijpers A, Hoffman T, et al. The five-factor model of the Positive and Negative Syndrome Scale: I. Confirmatory factor analysis fails to confirm 25 published five-factor solutions. Schizophr Res 2006; 85(1–3): 273–9PubMedGoogle Scholar
  72. 72.
    Fleischhacker WW, Kemmler G. The clinical relevance of percentage improvements on the PANSS score. Neuropsychopharmacology 2007; 32(11): 2435–6PubMedGoogle Scholar
  73. 73.
    Leucht S, Kane JM, Etschel E, et al. Linking the PANSS, BPRS, and CGI: clinical implications. Neuropsychopharmacology 2006; 31(10): 2318–25PubMedGoogle Scholar
  74. 74.
    Leucht S, Davis JM, Engel RR, et al. Defining ‘response’ in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology 2007; 32(9): 1903–10PubMedGoogle Scholar
  75. 75.
    Patel SR, Bakken S, Ruland C. Recent advances in shared decision making for mental health. Curr Opin Psychiatry 2008; 21(6): 606–12PubMedGoogle Scholar
  76. 76.
    Shumway M, Saunders T, Shern D, et al. Preferences for schizophrenia treatment outcomes among public policy makers, consumers, families, and providers. Psychiatr Serv 2003; 54(8): 1124–8PubMedGoogle Scholar
  77. 77.
    Green MF, Kern RS, Braff DL, et al. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the ‘right stuff’? Schizophr Bull 2000; 26(1): 119–36PubMedGoogle Scholar
  78. 78.
    McGurk SR, Mueser KT, Harvey PD, et al. Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment. Psychiatr Serv 2003; 54(8): 1129–35PubMedGoogle Scholar
  79. 79.
    Lehman AF, Carpenter Jr WT, Goldman HH, et al. Treatment outcomes in schizophrenia: implications for practice, policy, and research. Schizophr Bull 1995; 21(4): 669–75PubMedGoogle Scholar
  80. 80.
    Bustillo JR, Lauriello J, Keith SJ. Schizophrenia: improving outcome. Harv Rev Psychiatry 1999; 6(5): 229–40PubMedGoogle Scholar
  81. 81.
    Mortimer AM. Cognitive function in schizophrenia: do neuroleptics make a difference? Pharmacol Biochem Behav 1997; 56(4): 789–95PubMedGoogle Scholar
  82. 82.
    Danion JM, Rein W, Fleurot O. Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Am J Psychiatry 1999; 156(4): 610–6PubMedGoogle Scholar
  83. 83.
    Moller HJ. Novel antipsychotics and negative symptoms. Int Clin Psychopharmacol 1998; 13Suppl. 3: S43–7PubMedGoogle Scholar
  84. 84.
    Schmidt CJ, Sorensen SM, Kehne JH, et al. The role of 5-HT2A receptors in antipsychotic activity. Life Sci 1995; 56(25): 2209–22PubMedGoogle Scholar
  85. 85.
    Villeneuve A. Pathophysiology and treatment of negative symptoms. Can J Psychiatry 1994; 39 Suppl. 2: S53–8Google Scholar
  86. 86.
    Gallhofer B, Bauer U, Lis S, et al. Cognitive dysfunction in schizophrenia: comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs. Eur Neuropsychopharmacol 1996; 6Suppl. 2: S13–20PubMedGoogle Scholar
  87. 87.
    Sharma T, Mockler D. The cognitive efficacy of atypical antipsychotics in schizophrenia. J Clin Psychopharmacol 1998; 18Suppl. 1: 12S–9SPubMedGoogle Scholar
  88. 88.
    Tollefson GD. Cognitive function in schizophrenic patients. J Clin Psychiatry 1996; 57Suppl. 11: 31–9PubMedGoogle Scholar
  89. 89.
    Keefe RS, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry 2007; 64(6): 633–47PubMedGoogle Scholar
  90. 90.
    Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996; 153(3): 321–30PubMedGoogle Scholar
  91. 91.
    Harvey PD, Koren D, Reichenberg A, et al. Negative symptoms and cognitive deficits: what is the nature of their relationship? Schizophr Bull 2006; 32(2): 250–8PubMedGoogle Scholar
  92. 92.
    Gray JA, Roth BL. The pipeline and future of drug development in schizophrenia. Mol Psychiatry 2007; 12(10): 904–22PubMedGoogle Scholar
  93. 93.
    Gray JA, Roth BL. Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophr Bull 2007; 33(5): 1100–19PubMedGoogle Scholar
  94. 94.
    Laughren T, Levin R. Food and Drug Administration perspective on negative symptoms in schizophrenia as a target for a drug treatment claim. Schizophr Bull 2006; 32(2): 220–2PubMedGoogle Scholar
  95. 95.
    Lieberman JA. What the CATIE study means for clinical practice. Psychiatr Serv 2006; 57(8): 1075PubMedGoogle Scholar
  96. 96.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  97. 97.
    Burlingame GM, Dunn TW, Chen S, et al. Selection of outcome assessment instruments for inpatients with severe and persistent mental illness. Psychiatr Serv 2005; 56(4): 444–51PubMedGoogle Scholar
  98. 98.
    Heinrichs DW, Hanlon TE, Carpenter Jr WT. The quality of life scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull 1984; 10(3): 388–98PubMedGoogle Scholar
  99. 99.
    Mausbach BT, Moore R, Bowie C, et al. A review of instruments for measuring functional recovery in those diagnosed with psychosis. Schizophr Bull 2008; 35(2): 307–18PubMedGoogle Scholar
  100. 100.
    Patterson TL, Goldman S, McKibbin CL, et al. UCSD performance-based skills assessment: development of a new measure of everyday functioning for severely mentally ill adults. Schizophr Bull 2001; 27(2): 235–45PubMedGoogle Scholar
  101. 101.
    Harvey PD, Velligan DI, Bellack AS. Performance-based measures of functional skills: usefulness in clinical treatment studies. Schizophr Bull 2007; 33(5): 1138–48PubMedGoogle Scholar
  102. 102.
    Lehman AF. Measures of quality of life among persons with severe and persistent mental disorders. Soc Psychiatry Psychiatr Epidemiol 1996; 31(2): 78–88PubMedGoogle Scholar
  103. 103.
    Lehman AF. Quality of life issues and assessment among persons with schizophrenia. In: Moscarelli M, Rupp A, Sartorius N, editors. Handbook of mental health economics and health policy. Chichester: John Wiley & Sons, 1996: 69–79Google Scholar
  104. 104.
    Davidson L, O’Connell M, Tondora J, et al. The top ten concerns about recovery encountered in mental health system transformation. Psychiatr Serv 2006; 57(5): 640–5PubMedGoogle Scholar
  105. 105.
    Hogan TP, Awad AG, Eastwood R. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol Med 1983; 13(1): 177–83PubMedGoogle Scholar
  106. 106.
    Cramer J, Rosenheck R, Xu W, et al. Detecting improvement in quality of life and symptomatology in schizophrenia. Schizophr Bull 2001; 27(2): 227–34PubMedGoogle Scholar
  107. 107.
    Mohamed S, Rosenheck R, Swartz M, et al. Relationship of cognition and psychopathology to functional impairment in schizophrenia. Am J Psychiatry 2008; 165(8): 978–87PubMedGoogle Scholar
  108. 108.
    Narvaez JM, Twamley EW, McKibbin CL, et al. Subjective and objective quality of life in schizophrenia. Schizophr Res 2008; 98(1–3): 201–8PubMedGoogle Scholar
  109. 109.
    Hennekens CH, Hennekens AR, Hollar D, et al. Schizophrenia and increased risks of cardiovascular disease. Am Heart J 2005; 150(6): 1115–21PubMedGoogle Scholar
  110. 110.
    Remington G. Schizophrenia, antipsychotics, and the metabolic syndrome: is there a silver lining? Am J Psychiatry 2006; 163(7): 1132–4PubMedGoogle Scholar
  111. 111.
    Nasrallah HA, Targum SD, Tandon R, et al. Defining and measuring clinical effectiveness in the treatment of schizophrenia. Psychiatr Serv 2005; 56(3): 273–82PubMedGoogle Scholar
  112. 112.
    Harvey K, Catty J, Langman A, et al. A review of instruments developed to measure outcomes for carers of people with mental health problems. Acta Psychiatr Scand 2008; 117(3): 164–76PubMedGoogle Scholar
  113. 113.
    Zubin J, Steinhauer S, Condray R. Vulnerability to relapse in schizophrenia. Br J Psychiatry Suppl 1992; 18: 13–8PubMedGoogle Scholar
  114. 114.
    Lader M. What is relapse in schizophrenia? Int Clin Psychopharmacol 1995; 9Suppl. 5: 5–9PubMedGoogle Scholar
  115. 115.
    Leucht S, Barnes TR, Kissling W, et al. Relapse prevention in schizophrenia with new-generation antipsychotics: a systematic review and exploratory meta-analysis of randomized, controlled trials. Am J Psychiatry 2003; 160(7): 1209–22PubMedGoogle Scholar
  116. 116.
    Kane JM, Leucht S. Unanswered questions in schizophrenia clinical trials. Schizophr Bull 2008; 34(2): 302–9PubMedGoogle Scholar
  117. 117.
    Mouaffak F, Tranulis C, Gourevitch R, et al. Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia. Clin Neuropharmacol 2006; 29(1): 28–33PubMedGoogle Scholar
  118. 118.
    Remington G, Saha A, Chong SA, et al. Augmentation strategies in clozapine-resistant schizophrenia. CNS Drugs 2005; 19(10): 843–72PubMedGoogle Scholar
  119. 119.
    Beitinger R, Lin J, Kissling W, et al. Comparative remission rates of schizophrenic patients using various remission criteria. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(7): 1643–51PubMedGoogle Scholar
  120. 120.
    Leucht S, Beitinger R, Kissling W. On the concept of remission in schizophrenia. Psychopharmacology (Berl) 2007; 194(4): 453–61Google Scholar
  121. 121.
    Andreasen NC. Standardized remission criteria in schizophrenia. Acta Psychiatr Scand 2006; 113(2): 81PubMedGoogle Scholar
  122. 122.
    Addington J, Addington D. Symptom remission in first episode patients. Schizophr Res 2008; 106(2–3): 281–5PubMedGoogle Scholar
  123. 123.
    Gasquet I, Haro JM, Tcherny-Lessenot S, et al. Remission in the outpatient care of schizophrenia: 3-year results from the Schizophrenia Outpatients Health Outcomes (SOHO) study in France. Eur Psychiatry 2008; 23(7): 491–6PubMedGoogle Scholar
  124. 124.
    Lambert M, Schimmelmann BG, Naber D, et al. Prediction of remission as a combination of symptomatic and functional remission and adequate subjective well-being in 2960 patients with schizophrenia. J Clin Psychiatry 2006; 67(11): 1690–7PubMedGoogle Scholar
  125. 125.
    Novick D, Haro JM, Suarez D, et al. Symptomatic remission in previously untreated patients with schizophrenia: 2-year results from the SOHO study. Psychopharmacology (Berl) 2007; 191(4): 1015–22Google Scholar
  126. 126.
    Petersen L, Thorup A, Oqhlenschlaeger J, et al. Predictors of remission and recovery in a first-episode schizophrenia spectrum disorder sample: 2-year follow-up of the OPUS trial. Can J Psychiatry 2008; 53(10): 660–70PubMedGoogle Scholar
  127. 127.
    San L, Ciudad A, Alvarez E, et al. Symptomatic remission and social/vocational functioning in outpatients with schizophrenia: prevalence and associations in a cross-sectional study. Eur Psychiatry 2007; 22(8): 490–8PubMedGoogle Scholar
  128. 128.
    De Hert M, van Winkel R, Wampers M, et al. Remission criteria for schizophrenia: evaluation in a large naturalistic cohort. Schizophr Res 2007; 92(1–3): 68–73PubMedGoogle Scholar
  129. 129.
    van Os J, Drukker M, a Campo J, et al. Validation of remission criteria for schizophrenia. Am J Psychiatry 2006; 163(11): 2000–2PubMedGoogle Scholar
  130. 130.
    Lasser RA, Nasrallah H, Helldin L, et al. Remission in schizophrenia: applying recent consensus criteria to refine the concept. Schizophr Res 2007; 96(1–3): 223–31PubMedGoogle Scholar
  131. 131.
    Boden R, Sundstrom J, Lindstrom E, et al. Association between symptomatic remission and functional outcome in first-episode schizophrenia. Schizophr Res 2008; 107(2–3): 232–7PubMedGoogle Scholar
  132. 132.
    Helldin L, Kane JM, Karilampi U, et al. Remission in prognosis of functional outcome: a new dimension in the treatment of patients with psychotic disorders. Schizophr Res 2007; 93(1–3): 160–8PubMedGoogle Scholar
  133. 133.
    Del Vecchio P. Commentary: all we are saying is give people with mental illnesses a chance. Psychiatr Serv 2006; 57(5): 646PubMedGoogle Scholar
  134. 134.
    Dickerson FB. Commentary: disquieting aspects of the recovery paradigm. Psychiatr Serv 2006; 57(5): 647PubMedGoogle Scholar
  135. 135.
    Harrow M, Jobe TH. Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multi-follow-up study. J Nerv Ment Dis 2007; 195(5): 406–14PubMedGoogle Scholar
  136. 136.
    Liberman RP, Kopelowicz A. Recovery from schizophrenia: a concept in search of research. Psychiatr Serv 2005; 56(6): 735–42PubMedGoogle Scholar
  137. 137.
    Piat M, Sabetti J, Couture A. Do consumers use the word ‘recovery’? Psychiatr Serv 2008; 59(4): 446–7PubMedGoogle Scholar
  138. 138.
    President’s New Freedom Commission on Mental Health. Achieving the promise: transfoming mental health care in America. Rockville (MD): US Department of Health and Human Services, 2006 [online]. Available from URL: [Accessed 2009 Oct 21]
  139. 139.
    Remington G, Kapur S. Remission: what’s in a name? Am J Psychiatry 2005; 162(12): 2393–4PubMedGoogle Scholar
  140. 140.
    McGlashan TH. At issue: is natural selection rendering schizophrenia less severe? Schizophr Bull 2006; 32(3): 428–9PubMedGoogle Scholar
  141. 141.
    Faerden A, Nesvag R, Marder SR. Definitions of the term ‘recovered’ in schizophrenia and other disorders. Psychopathology 2008; 41(5): 271–8PubMedGoogle Scholar
  142. 142.
    McEvoy JP. Functional outcomes in schizophrenia. J Clin Psychiatry 2008; 69Suppl. 3: 20–4PubMedGoogle Scholar
  143. 143.
    Schooler NR. Relapse prevention and recovery in the treatment of schizophrenia. J Clin Psychiatry 2006; 67Suppl. 5: 19–23PubMedGoogle Scholar
  144. 144.
    Salyers MP, Godfrey JL, Mueser KT, et al. Measuring illness management outcomes: a psychometric study of clinician and consumer rating scales for illness self management and recovery. Community Ment Health J 2007; 43(5): 459–80PubMedGoogle Scholar
  145. 145.
    Leucht S, Lasser R. Theconcepts of remission and recovery in schizophrenia. Pharmacopsychiatry 2006; 39(5): 161–70PubMedGoogle Scholar
  146. 146.
    Agid O, Remington G, Kapur S, et al. Early use of clozapine for poorly responding first-episode psychosis. J Clin Psychopharmacol 2007; 27(4): 369–73PubMedGoogle Scholar
  147. 147.
    Harrow M, Jobe TH. Longitudinal studies of outcome and recovery in schizophrenia and early intervention: can they make a difference? Can J Psychiatry 2005; 50(14): 879–80PubMedGoogle Scholar
  148. 148.
    Ahmed M, Osser DN, Boisvert CM, et al. Rationale for emphasis on management over treatment of schizophrenia in clinical practice. Ann Pharmacother 2007; 41(4): 693–5PubMedGoogle Scholar
  149. 149.
    Masand PS, Narasimhan M. Improving adherence to antipsychotic pharmacotherapy. Curr Clin Pharmacol 2006; 1(1): 47–56PubMedGoogle Scholar
  150. 150.
    Naber D. Subjective effects of antipsychotic drugs and their relevance for compliance and remission. Epidemiol Psychiatr Soc 2008; 17(3): 174–6Google Scholar
  151. 151.
    Perkins DO, Johnson JL, Hamer RM, et al. Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophr Res 2006; 83(1): 53–63PubMedGoogle Scholar
  152. 152.
    Malla AK, Norman RM, Joober R. First-episode psychosis, early intervention, and outcome: what have we learned? Can J Psychiatry 2005; 50(14): 881–91PubMedGoogle Scholar
  153. 153.
    Demily C, Franck N. Cognitive remediation: a promising tool for the treatment of schizophrenia. Expert Rev Neurother 2008; 8(7): 1029–36PubMedGoogle Scholar
  154. 154.
    Brown PC, Tucker WM. Measuring the effectiveness of outpatient care. Psychiatr Serv 2005 Mar; 56(3): 241PubMedGoogle Scholar
  155. 155.
    Dickerson FB, Brown CH, Daumit GL, et al. Health status of individuals with serious mental illness. Schizophr Bull 2006; 32(3): 584–9PubMedGoogle Scholar
  156. 156.
    Jobe TH, Harrow M. Long-term outcome of patients with schizophrenia: a review. Can J Psychiatry 2005; 50(14): 892–900PubMedGoogle Scholar
  157. 157.
    Robinson DG, Woerner MG, McMeniman M, et al. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry 2004; 161(3): 473–9PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Gary Remington
    • 1
    • 2
    • 3
  • George Foussias
    • 1
    • 2
    • 3
  • Ofer Agid
    • 1
    • 3
  1. 1.Department of Psychiatry, Faculty of MedicineUniversity of TorontoTorontoCanada
  2. 2.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  3. 3.Schizophrenia Program, Centre for Addiction and Mental HealthTorontoCanada

Personalised recommendations