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Solian ® in schizophrenia an overview

Solian ® in schizophrenia an overview. Mode of action. blocks D 2 -receptors. does not block D 1 -receptors. Solian ®. Solian’s D 2 -D 3 selectivity is consistent with atypicality The dopamine cortico-subcortical imbalance in schizophrenia. Positive symptoms attributable to

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Solian ® in schizophrenia an overview

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  1. Solian® in schizophreniaan overview

  2. Mode of action

  3. blocks D2-receptors does not block D1-receptors Solian® Solian’s D2-D3 selectivity is consistent with atypicalityThe dopamine cortico-subcortical imbalance in schizophrenia Positive symptoms attributable to • high dopamine release • overstimulated D2-receptors in limbic system Deficit symptoms attributable to • low dopamine release • understimulated D1-receptors in frontal cortex Weinberger DR. Arch Gen Psychiatry 1987 Davis KL, Kahn RS et al. Am J Psychiatry 1991

  4. Solian® a pure D2-D3 antagonist alleviates positive symptoms In limbic region postsynaptic: predominantly D2-D3 receptors blocked by Solian® -> less positive symptoms Differences in pharmacological activities do not necessarily imply difference in efficacy/tolerability Kapur S. in: “Dopamine in the pathophysiology of schizophrenia.” 2003

  5. Solian® a pure D2-D3 antagonist alleviates negative symptoms also In prefrontal region presynaptic: predominantly D2-D3 receptors -> feed-back blocked by Solian® -> enhanced dopamine release postsynaptic: predominantly D1 receptors D1 receptors are NOT blocked by Solian® net result: alleviating hypofrontality and negative symptoms Differences in pharmacological activities do not necessarily imply difference in efficacy/tolerability Kapur S. in: “Dopamine in the pathophysiology of schizophrenia.” 2003

  6. Solian’s pure D2-D3 antagonismminimizes neuroreceptor mediated side-effectsAntipsychotics receptors binding profile Differences in pharmacological activities do not necessarily imply difference in efficacy/tolerability Adapted from Duncan et al. 1989, Sunhara et al. 1991, Sokoloff et al. 1992, Bymaster et al. 1996, Schotte et al. 1996, Schoemaker et al. 1997 + package inserts

  7. Efficacy

  8. Few atypicals with proven superiority over conventionalsEffect size versus conventional antipsychotics * a 0,25 effect size unit corresponds to 4-6 PANSS points or 3-4 BPRS points change meta-analysis of randomised efficacy trials: 10 atypical versus conventional antipsychotics 124 randomised controlled efficacy trials (n = 18 272 schizophrenic patients) Davis JM et al. Arch Gen Psychiatry 2003

  9. Efficacy: positive symptomsEffect size versus conventional antipsychotics meta-analysis of 18 randomised controlled trials, schizophrenic patients Leucht S et al. Am J Psychiatry 2002

  10. -52% NS Acute exacerbation: comparable to risperidoneEfficacy on PANSS positive items double blind randomised, non-inferiority trial t = 8 weeks, n = 228 acute exacerbations of schizophrenia DSM III R Peuskens J, Bech P, Möller HJ, Bale R et al. Psychiatry Research 1999

  11. 76,9% 71,9% 65,3% Responders rate compared to risperidone (in %) responders = improvement ≥ 50% (PANSS, BPRS) or “much” to “very much” improved (GCI) n = 244 patients with chronic schizophrenia and a recent exacerbation Sechter D et al. Neuropsychopharmacol 2002

  12. Acute exacerbation: at least as effective as olanzapineEfficacy on BPRS subscales double blind randomised, non-inferiority trial, BPRS: primary endpoint t = 6 months, n = 377 acute exacerbations of schizophrenia DSM IV Mortimer A et al. Int Clin Psychopharmacol 2004

  13. Efficacy: negative symptomsEffect size versus conventional antipsychotics meta-analysis of 18 randomised controlled trials, schizophrenic patients Leucht S et al. Am J Psychiatry 2002

  14. 29,0 39,9 40,9 43,0 43,6 49,5 Improving the whole range of negative symptomsSANS subscores randomised double blind multicenter versus placebo, n = 141 schizophrenic patients (DSM III R), with predominantly negative symptoms (SANS ≥ 60 and SAPS ≤ 50) Lôo H, Poirier MF, Théron M, Rein W, Fleurot O. Br J Psychiatry 1997

  15. Efficacy: depression/anxiety subscore versus haloperidol and risperidoneReduction BPRS depression/anxiety subscore pooled results of 3 previously published randomised studies, n = 612 chronic or subchronic schizophrenia (DSM III R and IV), acute exacerbation, (disorganised, paranoid of undifferentiated type), t = 4 - 8 weeks Peuskens J, Möller HJ, Puech A. Eur Neuropsychopharm 2002 Möller H, Boyer P, Fleurot O, Rein W. Psychopharmacol 1997 Puech A, Fleurot O, Rein W. Acta Psychiatr Scand 1998 Peuskens J, Bech P, Möller HJ et al. Psychiatry Res 1999

  16. p = 0,033 49% Quality of lifeversus risperidoneSocial and Occupational Functioning Assessment Scale (SOFAS) double blind randomised, non-inferiority study n = 309 patients with chronic schizophrenia DSM IV, recent deterioration at entry Sechter D et al. Neuropsychopharmacol 2002

  17. Tolerability

  18. -0,16 -0,9 NS NS double blind randomised study, n = 310 acute exacerbations of schizophrenia DSM IV Sechter D et al. Neuropsychopharmacol 2002 double blind randomised study, n = 377 schizophrenic patients DSM IV Mortimer A et al. Int Clin Psychopharmacol 2004 Low EPS profile (AIMS)

  19. High atypicality: effectiveness with minimal EPSSolian’s fast off-rate from the D2-receptorTime needed for 50% release from cloned D2-receptors1 • an effective attenuation of the tonic dopamine transmission -> antipsychotic efficacy • with less distortion of the bursts of the phasic physiological signalling2 -> minimal EPS Differences in pharmacological activities do not necessarily imply difference in efficacy/tolerability 1. Seeman P. Can J Psychiatry 2002. 2. Kapur and Seeman 2001 Kapur S in “Dopamine in the pathophysiology of schizophrenia”. Ed: Kapur S, Lecrubier Y at Martin Dunitz Editions, UK 2003 ISBN 1 84184 366 0

  20. 0,80 Solian® induces little weight gainWeight gain at 10 weeks Allison DB, Mentore JL. Am J Psychiatry 1999, Taylor DM, McAskill R. Acta Psychiatr Scand 2000 Data for amisulpride: Leucht S, Wagenpfeil S et al. Psychopharmacol 2004

  21. p < 0,05 p < 0,0004 20,6% 18% double blind randomised study, n = 309 chronic schizophrenia DSM IV, t = 6 months Sechter D et al. Neuropsychopharmacol 2002 double blind randomised study, n = 377 schizophrenic patients DSM IV, t = 6 months Mortimer A et al. Int Clin Psychopharmacol 2004 Clinically relevant weight gain versus risperidone and olanzapine

  22. Antipsychotic-induced diabetes mellitus • Emergence of new onset diabetes attributable to antipsychotic use • multiple case reports1 • - confirmed in a case control study2 Different antipsychotics unequally involved - confirmed in a prospective randomised double blind study3 • No published report about a potential relation between Solian® and hyperglycemia or ketoacidosis4 • as of May 2003, 650 million treatment days worldwide (IMS figures) prospective randomised double blind studyn = 101, initially non-diabetic patients, hospitalised for antipsychotic treatment instauration 1. Consensus statement ADA, APA, AACE, NAASO. Diab Care 2004 2. Koro CE, Fedder DO et al. BMJ 2002 3. Lindenmayer JP, Czobor P et al. Am J Psychiatry 2003 4. Mir S,Taylor D. Int Clin Psychopharmacol 2001

  23. Prolactin elevation with Solian®2 • not dose dependent • decreases as treatment continues • returns to pretreatment levels within 3 months after treatment stop Endocrine/sexual side effectsComparison with risperidone1 pooled data from 11 randomised clinical studiesexposure: 125 days Solian®, 47 days risperidone 1. Coulouvrat C, Dondey-Nouvel L. Int Clin Psychopharmacol 1999 2. Schlösser R, Gründer G et al. Neuropsychobiology 2002

  24. Pharmaco-economics

  25. 24,7 17,2 Solian® 400-1000 mg/d Total = 41,9 days of hospitalisation 42,3 10,4 risperidone 4-10 mg/d Total = 52,7 days of hospitalisation full time hospitalisation part time hospitalisation Shift to ambulatory careSolian® versus risperidone double blind randomised study n = 198 (at 6 months), patients with chronic schizophrenia DSM IV and a recent exacerbation Knapp M, Spiesser L, Jourdan S. Submitted for publication. Data from Sechter et al. Neuropsychopharmacol 2002

  26. Posology instructions

  27. Start Solian® Without titration Former antipsychotic (conventional or atypical) Tapering off Solian®: easy to start… easy to switch to Without titration, immediately at therapeutic dose§ • -> start Solian® • at the therapeutic dose required • - without titration§ • -> taper off the old antipsychotic • over a 3-4 week period* (by approximately 30-50% every 3-7 days)1 • without washout period2 • - previous concomitant anticholinergics should also be stopped progressively 1. Peuskens J. J Int Clin Psychopharmacol 2000, 15(4):S15-S19 2. Solian® Product Information, June 2001 § in patients with renal impairment dose should be adjusted according to Product Information *Slow tapering off the young, the elderly, recently relapsed, patients on clozapine, those previously treated with doses of low potency neuroleptics, patients difficult to stabilise

  28. Solian®: easy to useClear dosing1 Acute exacerbations Productive states Stabilisation Usual maintenance dose Chronic psychosis Predominantly negative symptoms 800 mg/day (BID) (to max 1200 mg/d) 400 mg/day (OD) 300 to 50 mg/day (OD) If positive symptoms reappear: increase dose to previous stabilizing level For acute psychotic episodes, doses should be adjusted according to individual response. For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive symptoms. Maintenance treatment should be established individually with the minimally effective dose. For patients characterized by predominant negative symptoms, oral doses between 300 and 50 mg / day are recommended. Doses should be adjusted individually. 1. Lecrubier Y et al. Neuropsychobiology 2001 and Peuskens J et al. Psy Res 1999

  29. Pharmacokinetics Drug/drug interactions

  30. Solian® is not metabolized via the CYP450 system Gillet et al. Neuropsychopharm 10/2000,S331-S332 Package Inserts

  31. Solian® is not metabolized via the CYP450 system (continued) Gillet et al. Neuropsychopharm 10/2000,S331-S332 Package Inserts

  32. Solian® at a glance Pure D2-D3 selectivity: a unique mode of action • restoring the dopamine imbalance in schizophrenia • minimising side-effects mediated by other neuroceptors A high limbic over striatal receptor affinity and a fast off-rate from the D2-receptor • explaining a low EPS level In general a high effect size on schizophrenia symptoms • one of the few atypicals with proven efficacy over conventionals In acute situations • fast onset of antipsychotic action involving the whole range of BPRS subscales • easy and clear posology instructions • easy manageable combination with benzodiazepines whenever necessary

  33. Solian® at a glance In predominant negative symptoms • acting on the whole range of negative symptoms • improving depression/anxiety without affecting cognition On the longer term • low weigth gain - low incidence of metabolic side-effects • low sexual / endocrine side effects in daily practice • respecting quality of life / facilitating socialisation • manageable drug-drug interactions Value for money • less hospitalisation days / shift towards ambulatory care • good therapy adherence

  34. סוליאן בסל הבריאות 1.לחולה סכיזופרניה מעל גיל 18 שנים,ובהתקיים אחד מהתנאים האלה : א. החולה מוגדר כבעל קווי התנהגות תוקפניים,וכטיפול ראשון. ב. החולה לא הגיב לטיפול ב risperidoneאו פיתח תופעות לוואי קשות לטיפול האמור. 2. לחולה מתחת לגיל 18 שנים הסובל מסכיזופרניה או מפסיכוזה אחרת, וכטיפול ראשון.

  35. סוליאן בקופות קופת חולים כללית – בהשתתפות 10% של המטופל קופת חולים מכבי- בהשתתפות 15% של המטופל קופת חולים לאומית – השתתפות 15% של המטופל קופת חולים מאוחדת- בהשתתפות 15% של המטופל

  36. תודה על ההקשבה

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