Remission in Schizophrenia: Clinical and PsychoSocial Dimensions Prof Yoram BARAK, MD, MHA.

1. Remission in Schizophrenia: Clinical and PsychoSocial Dimensions Prof Yoram BARAK, MD, MHA. ABARBANEL M.H.C. Bat-Yam, ISRAEL Prof Y Barak

2. Remission in Schizophrenia the Road toRecovery Prof Y Barak

3. Current and Future Directions Cure Recovery Maintain (normal without treatment) Sustained Remission > 6 months (“normal”) Remission/ Functional Remission Resolution Attain Stable (virtual absence of diagnostic symptoms for 6 monts) Response (no obvious evolution) (virtual absence of diagnostic symptoms) Acute Phase (decrease of symptoms) (ill) Prof Y Barak

4. Long-term outcomes in schizophrenia Focus on functionality Potential for remission 2000+ Increase ‘stable’ periods Minimise negative symptoms 1990s Reduce relapse Minimise positive symptoms 1980s ‘Survive’ out of hospital De-institutionalisation Improve self-care Reduce aggression Reduce self-injury 1960-70s Prof Y Barak Pre-1960s

5. RESPONSE RELAPSE Increasing severity Diagnostic threshold Symptoms ‘mild’ or less REMISSION RESOLUTION ‘Normalcy’ threshold Symptoms absent 6 months Expanded model of remissionin schizophrenia Prof Y Barak Peuskens J & Kane J. In preparation.

6. Recovery Functional and Social Autonomy Remission Functional, Quality of Life Maintaining Stability Response Remission in Schizophrenia Improvement dependency Prof Y Barak Adapted from Weiden et al, J Clin Psych 1996; 57: 53-60

7. What is Remission? • Remission in nonpsychiatric illnesses: • The reduction or the complete absence of disease symptoms. • Remission in psychiatric illnesses: • Defined not by the complete absence of symptoms but by minimal symptoms with mild disability. Prof Y Barak

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9. StoRMi - Study Design: • Schizophrenia or any other psychiatric disorders requiring long-term antipsychotic treatment • Symptomatically stable patients on any previous antipsychotic medication for 1 month • Length of treatment: 6 months +6 months • 22 participating countries • Number of recruited patients: 1,909 Prof Y Barak

10. Treatment • 25 מ"ג של זריקת ריספרידון לטווח ארוך ניתנה אחת לשבועיים במשך 6 חודשים. • באם לא הייתה הטבה בסימפטומים או אם לא הושגה תגובה מספקת לטיפול, ניתן היה להעלות במינון 2-4 שבועות לאחר הזריקה האחרונה למינון של 37.5 או 50 מ"ג אחת לשבועיים. • הטיפול האנטיפסיכוטי הקודם ניתן במשך 3 שבועות הראשונים לזריקה. Prof Y Barak

11. Treatment change from Other 87 = 5% Risperidone Conv. Oral 254 = 14% Olanzapine Quetiapine Amisulpiride Risperidone 732 = 39% Ziprasidone Conv Depot Conv. Depot 813 = 43% Conv. Oral Other More than 1 drug per patientpossible Olanzapine 192 = 10% Quetiapine 49 = 3% Ziprasidone 6 = 0% Amisulpiride 57 = 3%

12. StoRMi trial תוצאות Prof Y Barak

13. PANSS total score: by baseline severity PANSS Ranges at Baseline Moderate >74.5- 106.5 Mild < 74.5 Severe > 106.5 58 91 126 56 116 86 54 106 81 52 96 76 50 86 71 48 76 66 46 66 Baseline Baseline Endpoint Endpoint Months 1 Months 3 Months 6 Baseline Months 1 Months 3 Months 6 Months 1 Months 3 Months 6 Endpoint P  0.001 at all timepoints compared to baseline Prof Y Barak

14. StoRMi -סיכום תוצאות יעילות • ספקטרום רחב של חולים פסיכוטיים עשוי ליהנות מהמעבר ל RC. • חולים יציבים הראו שיפור נוסף בבקרה על הסימפטומים וסבילות לטיפול. • איכות החיים והפונקציונליות של החולים מצביעה על איכות טיפולית חדשה. • התחלת טיפול עם RC נמצאה יעילה. Prof Y Barak

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16. “Remission in Schizophrenia:Proposed Criteria and Rationale for Consensus”Am J Psychiatry 2005; 162:441–449 • Nancy C. Andreasen, M.D., Ph.D. • William T. Carpenter, Jr., M.D. • John M. Kane, M.D. • Robert A. Lasser, M.D. • Stephen R. Marder, M.D. • Daniel R. Weinberger, M.D. Prof Y Barak

17. Abstract (1) New advances in the understanding of schizophrenia etiology, course, and treatment have increased interest on the part of patients, families, advocates, and professionals in the development of consensus-defined standards for clinical status and improvement, including illness remission and recovery. Prof Y Barak

18. Abstract (2) As demonstrated in the area of mood disorders, such standards provide greater clarity around treatment goals, as well as an improved framework for the design and comparison of investigational trials and the subsequent evaluation of the effectiveness of interventions. Prof Y Barak

19. Abstract (3) Unlike the approach to mood disorders, however, the novel application of the concept of standard outcome criteria to schizophrenia must reflect the wide heterogeneity of its long-term course and outcome, as well as the variable effects of different treatments on schizophrenia symptoms. Prof Y Barak

20. Abstract (4) As an initial step in developing operational criteria, an expert working group reviewed available definitions and assessment instruments to provide a conceptual framework for symptomatic, functional, and cognitive domains in schizophrenia as they relate to remission of illness. Prof Y Barak

21. Abstract (5) The first consensus-based operational criteria for symptomatic remission in schizophrenia are based on distinct thresholds for reaching and maintaining improvement, as opposed to change criteria, allowing for alignment with traditional concepts of remission in both psychiatric and nonpsychiatric illness. Prof Y Barak

22. Abstract (6) This innovative approach for standardizing the definition for outcome in schizophrenia will require further examination of its validity and utility, as well as future refinement, particularly in relation to psychosocial and cognitive function and dysfunction. These criteria should facilitate research and support a positive, longer-term approach to studying outcome in patients with schizophrenia. Prof Y Barak

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24. Combining Clinical & PsychoSocial Domains:The Israeli Project • We aim to create a 2-pronged scale • Clinical – as defined by Andreasen et al. • Psychosocial –reflecting: • Quality of Life • Needs • I-ADL Prof Y Barak

25. Remission Criteria in Schizophrenia Patient achieves intensity level… • …PANSS scale level of mild or less 1 Absent 2 Minimal 3 Mild 4 Moderate 5 Moderate severe 6 Severe 7 Extreme • Time criteria of at least 6 months • …on all 8 symptom items • P1 Delusions • P2 Conceptual disorganization • P3 Hallucinatory behavior • G9 Unusual thought content • G5 Mannerisms and posturing • N1 Blunted affect • N4 Social withdrawal • N6 Lack of spontaneity/flow of conversation Prof Y Barak

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31. European Neuropsychopharmacology (2007) 17, iii Contents: Improved Understanding and Treatment of Schizophrenia. From the symposium ‘Acute to Long-term Treatment in Schizophrenia: Effectiveness is a Moving Target’ at the 19th European Congress of Neuropsychopharmacology, September 16–20 2006, Paris, France Prof Y Barak

32. European Neuropsychopharmacology (2007) 17, iii • Risk factors for schizophrenia — All roads lead to dopamine. M. Di Forti, J.M. Lappin and R.M. Murray (UK) S101 • Management of agitation in the acute psychotic patient — Efficacy without excessive sedation. F. Can˜as (Spain) S108 • The stable patient with schizophrenia — From antipsychotic effectiveness to adherence. P. Thomas (France) S115 • The long term — Maximising potential for rehabilitation in patients with schizophrenia. A. Fagiolini and A. Goracci (USA, Italy) S123 Prof Y Barak

33. The long term — Maximising potential for rehabilitation in patients with schizophrenia. Aims of rehabilitation in schizophrenia: Therapeutic programmes that are developed to optimize the potential for rehabilitation in patients with schizophrenia should aim to maximise the patients' daily functioning in an attempt to enable them to engage in employment and increase their self-sufficiency. Rehabilitation should also attempt to enable patients with schizophrenia to integrate into society, improving their social interactions and activities. The complex nature of health-related quality of life (QoL) in schizophrenia patients has been recognised and another aim of rehabilitation is to improve this aspect. All of these aims should be considered when evaluating the effectiveness of any treatment that patients receive. Prof Y Barak

34. The long term — Maximising potential for rehabilitation in patients with schizophrenia. Aims of rehabilitation in schizophrenia: The employment prospects for patients with schizophrenia may be impeded by clinical symptoms, and data from the CATIE study clearly illustrate this (Rosenheck et al., 2006). No employment activity was reported for 72.9% of the patients in the month before the baseline assessment; 14.5% of the patients had been engaged in competitive employment, and the remaining 12.6% had participated in non-competitive employment. Less severe symptoms of schizophrenia, better neurocognitive functioning and higher intrapsychic functioning scores (which evaluated a range of psychological characteristics) were associated with participation in employment. Prof Y Barak

35. The long term — Maximising potential for rehabilitation in patients with schizophrenia. Aims of rehabilitation in schizophrenia: Sociocultural context may be one of the major factors that can influence rehabilitation in patients with schizophrenia, and policy makers should give consideration to the creation of resources for the rehabilitation of schizophrenia patients within communities that complement the success that can be achieved with regard to reducing their psychotic symptoms (Mubarak, 2005). Prof Y Barak

36. The long term — Maximising potential for rehabilitation in patients with schizophrenia. Aims of rehabilitation in schizophrenia: Almost half (46.5%) of schizophrenia patients report dissatisfaction with their overall QoL. By creating opportunities to improve social functioning, it may also be possible to improve patients' subjective QoL; treatment that addresses psychotic symptoms in isolation from these factors may not facilitate QoL improvements. Prof Y Barak

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38. Real World research Findings Schizophr Res. 2007 Mar 27; [Epub ahead of print] Remission in prognosis of functional outcome: A new dimension in the treatment of patients with psychotic disorders. Helldin L, Kane JM, Karilampi U, Norlander T, Archer T. Prof Y Barak

39. Real World research Findings INTRODUCTION: The aim of the present study was to investigate whether or not the new concept of remission in the treatment of schizophrenia is of importance for functional outcome. The hypothesis was that patients having attained remission would function at a higher level and have a lower care requirement than those who had not attained remission. Prof Y Barak

40. Real World research Findings MATERIALS AND METHODS: Remission is defined through the application of the Positive and Negative Syndrome Scale (PANSS) instrument whereby none of the eight chosen items, representing core symptoms, should be found to present a value exceeding 3 points. The utility of attaining the severity criteria for remission, or not, was examined with regard to activity of daily living (ADL) ability, establishment of social functioning and social network, and amount of health care and community support that the patient consumed. Two hundred and forty-three patients were examined, of whom 93 patients (38%) had attained remission and 150 patients (62%) had not. The present patient population, consisting of 50% of all available patients with schizophrenia spectrum disorder within a homogeneous catchment area in NU Health Care, western Sweden, meeting the right diagnostic criteria, were in their habitual condition and were unaffected by any other functionally debilitating disorder, in particular dementia. As a control patients diagnoses were used as the independent variable to exclude that they better explain outcome than remission. Prof Y Barak

41. Real World research Findings RESULTS: It was found that patients that attainted the specified remission criteria showed a significantly superior outcome in all assessed areas with regard to activity of daily life, social functioning in society and consumption of health care. Remission patients functioned more effectively in social contexts in association with superior education, more often had occupations, possessed more established social networks and were more likely to be found living under family-like conditions. They exhibited a lower need for support in order to fulfill their everyday activities. Also, patients in remission required markedly less health care resources, both in the form of psychiatric treatment and community habitation support. In contrast diagnoses only made difference in 4 of 14 outcome parameters. Prof Y Barak

42. Real World research Findings DISCUSSION: The results suggest that the concept of remission has important implications for the treatment of patients with chronic psychosis. One possible conclusion is that if more patients attain remission, the patient's and society's burden resultingfrom the illness will decrease. Prof Y Barak

43. תודה על ההקשבה ו: שאלות Prof Y Barak