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Barriers to achieve remission and recovery in schizophrenia

Barriers to achieve remission and recovery in schizophrenia. Prof Köksal Alptekin MD Dept of Psychiatry Dokuz Eylül Univ ersity School of Medicine İzmir -TURKEY. GAMIAN-Europe Regional Seminar: Psychosocial Recovery, Budapest 2011. koksal.alptekin@deu.edu.tr.

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Barriers to achieve remission and recovery in schizophrenia

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  1. Barriers to achieve remission and recovery in schizophrenia Prof Köksal Alptekin MD Dept of Psychiatry Dokuz Eylül University School of Medicine İzmir-TURKEY GAMIAN-Europe Regional Seminar: Psychosocial Recovery, Budapest 2011 koksal.alptekin@deu.edu.tr

  2. Barriers to achieve remission and recovery in schizophrenia • Treatment effectiveness • Treatment side effects and early death • Combined antipsychotics use • Treatment adherence • Cognitive deficits and psychosocial functioning

  3. One-year follow up study of schizophrenia patients: a multicenter, naturalistic design • 382 patients with DSM-IV schizophrenia • 44 % patients were followed-up for a year • Total BPRS: Baseline: 53.11, 12th Month: 42.11 BPRS scores

  4. Predictor Factorsof Disability(Multiple Linear Regression Analysis) B Std.Eror Beta t___ Negative symp. 0.391 0.155 0.302 2.304* DUP 0.428 0.181 1.181 2.365* (Constant) 3.513 1.001 ----- 2.429__ * p < 0.05 ( DUP : Duration of Untreated Psychosis) (Alptekin et al. 2005, Psychiatry Research)

  5. Only 14 %met fullrecovery criteria for 2 years or longer. • Better cognitive functioning was associated with full recovery (adequatesocial/vocational functioning, and symptomremission) • Shorter duration of psychosisbefore study entry predicted both fullrecovery and symptom remission.

  6. Remission & recovery in schizophrenia • Duration of untreated psychosis • Cognitive functions • Negative symptoms

  7. Discontinuation Rates CATIE study1 56 44 All drugs (n=382)2* Patients % *Graph showing discontinuation rate for patients on various antipsychotic drug combinations for 12 month period; CATIE study shows discontinuation rate over 18 months 1. Lieberman JA et al. N Engl J Med 2005; 353: 1209–23. 2. Alptekin K et al. J Psych Res 2005; 135:101–11

  8. 150 double-blind, mostly short-term studies, • 21 533 participants • Four of these drugs were better than FGAs for overall efficacy, with small to medium effect sizes • Amisulpride: −0·31 [95% CI −0·44 to −0·19,p<0·0001] • Clozapine: −0·52 [−0·75 to −0·29, p<0·0001] • Olanzapine: −0·28 [−0·38 to −0·18, p<0·0001] • Risperidone: −0·13 [−0·22 to −0·05, p=0·002])

  9. CATIE Phase 2 Efficacy:Treatment Discontinuation Total p-value = 0.010*KLZ vs OLZ p=0.019KET vs OLZ p=0.004 KLZ vs RIP p=0.003 1 0.8 0.6 Treatment continuation rates 0.4 0.2 0 0 3 6 9 12 15 18 MONTHS Klozapin (N=45) Ketiapin (N=14) Olanzapin (N=17) Risperidon (N=14) McEvoy JP, et al. Am J Psychiatry 2006;163:600-610.

  10. 78 Randomized Double Blind Studies, 13558 patients (PANSS Total Scores) Clozapine (400 mgr/gün) ≥ Risperidone (Leucht ve ark., Am J Psych 2008)

  11. Sertindole r = 0.34, N=1, n = 424 0 0,1 0,2 0,3 0,4 EPS – SGA&FGA Amisulpride r = 0.25, N=12, n = 1599 Olanzapine r = 0.39, N=3, n = 2694 Quetiapine r = 0.32, N=2, n = 757 Risperidone r = 0.14, N=12, n = 2421 (r) Leucht et al. Am J Psychiatry 2002

  12. Antipsychotics & Cognitive Functions (Meta-analysis) First & Second Generation antipsychotics *Between 1990-1998, 15 studies. 3 randomized double-blind and 12 open label. SGA BETTER Keefe 1999 • FGA & Placebo (Effect Size:0.22) * • FGA & SGA (14 studies) ** • Clozapine, Olanzapine, Quetipine, Risperidone • SGA BETTER (Effect Size: 0.24) * Mishara ve Goldberg, 2004, **Woodward ve ark. 2005 Verbal fluency, attention, executive functions, Learning and information processing speed Effect Size: 0.22 / 0.24 Correlated to motor dysfunctions and EPS

  13. One-year follow up study of schizophrenia patients: a multicenter, naturalistic design • Combined antipsychotics use • “dirty little secret” (Stahl)

  14. Anıl Yağcıoğlu ve ark., J Clin Psychiatry 2006 PANSS Positive : Prolactine Levels : p =0.002 p0.0001 PANSS POS LS Means Prolactin level (ng/ml) LS Means Time p 0.0001 Treatment group 0.0001 Time p 0.0001 Treatment group x time p 0.05 Treatment group x time p 0.0001

  15. Compared to the general population, persons with major mental illness typically lose more than 25 years of normal life span Colton CW, Manderscheid RW. Prev Chronic Dis [serial online] 2006 Apr [date cited]. Available from: URL:http://www.cdc.gov/pcd/issues/2006/apr/05_0180.htm, (Newcomer J Clin Psych)

  16. Physical Health: A Major Concern to Psychiatristsand Patients Sexual dysfunction Metabolic abnormalities Weight change Sedation EPS        ? • 3,764 respondents, across 12 European countries (2006) • 10-question survey on aspects of physical health in schizophrenia • Physical health monitoring and the impact of antipsychotic therapy • Only 66 % reported that they were monitoring weight. 1. Saravane D et al. European Psychiatry 2007; S101–S220: Abstract # P130. 2. NICE Guidelines. 3. Hofer A et al. J Clin Psychiatry 2002; 63:49–53. 4. Angermeyer MC et al. Psychiatr Prax 2000.

  17. Doctors and lay people differ in their attitudestowards weight gain • Patients may encounter negative public attitudes towards antipsychotics and strong pressure to stop medication in the event of side effects *** p  0.001 Helbling J et al. BMC Psychiatry 2006;6:42

  18. Treatment Nonadherence • Increase relapse rates • Frequent hospitalization • Poor prognosis • Impaired psychosocial functioning • Poor quality of life

  19. J Clin Psychiatry 2003;64:10–3 J Clin Psychiatry 2004;65:1211–8 • Insight • Cognitivedysfunctions • Patient’s feelings • Side effects • Efficacy Nonadherence Doctor/patient relationship - a working therapeutic alliance

  20. Conclusions.1 : • Clozapine seems quite better • Dose is very relevant regarding remission of symptoms • However patients are still symptomatic. • Far away from recovery issues mainly due to inefficacy of available antipsychotics over cognitive dysfunctions • Treatment side effects, weight gain, early death issue

  21. Conclusions.2 : • Efficacy in remission of positive symptoms • Less efficacy in improving negative symptoms and especially cognitive dysfunctions • Receptors underlying cognitive dysfunctions are not clear • New medicines are requiredto treat both psychosis and cognitive dysfunctions or future treatment of schizophrenia may happen by combining SGAs and new medicines which improve cognitive dysfunctions.

  22. koksal.alptekin@deu.edu.tr

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