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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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slide3

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

solian a pure d 2 d 3 antagonist alleviates positive symptoms
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

solian a pure d 2 d 3 antagonist alleviates negative symptoms also
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

slide6
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

slide8
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

efficacy positive symptoms effect size versus conventional antipsychotics
Efficacy: positive symptomsEffect size versus conventional antipsychotics

meta-analysis of 18 randomised controlled trials, schizophrenic patients

Leucht S et al. Am J Psychiatry 2002

acute exacerbation comparable to risperidone efficacy on panss positive items

-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

responders rate compared to risperidone in

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

acute exacerbation at least as effective as olanzapine efficacy on bprs subscales
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

efficacy negative symptoms effect size versus conventional antipsychotics
Efficacy: negative symptomsEffect size versus conventional antipsychotics

meta-analysis of 18 randomised controlled trials, schizophrenic patients

Leucht S et al. Am J Psychiatry 2002

improving the whole range of negative symptoms sans subscores

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

slide15
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

quality of life versus risperidone social and occupational functioning assessment scale sofas

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

low eps profile aims

-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)
slide19

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

solian induces little weight gain weight gain at 10 weeks

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

clinically relevant weight gain versus risperidone and olanzapine

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
antipsychotic induced diabetes mellitus
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

endocrine sexual side effects comparison with risperidone 1

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

shift to ambulatory care solian versus risperidone

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

solian easy to start

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

solian easy to use clear dosing 1
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

solian is not metabolized via the cyp450 system
Solian® is not metabolized via the CYP450 system

Gillet et al. Neuropsychopharm 10/2000,S331-S332 Package Inserts

solian is not metabolized via the cyp450 system continued
Solian® is not metabolized via the CYP450 system (continued)

Gillet et al. Neuropsychopharm 10/2000,S331-S332 Package Inserts

slide32
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

slide33
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

slide34
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.

slide35
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