Solian Slide Kit

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Solian in schizophreniaan overview
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Mode of action
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Solians 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
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Solian a pure D2-D3 antagonist alleviates
positive symptoms
In limbic region postsynaptic predominantly
D2-D3 receptors blocked by Solian -gt 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
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Solian a pure D2-D3 antagonist alleviates
negative symptoms also
In prefrontal region presynaptic predominantly
D2-D3 receptors -gt feed-back blocked by
Solian -gt 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
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Solians pure D2-D3 antagonismminimizes
neuroreceptor mediated side-effectsAntipsychotic
s receptors binding profile
Receptor Subtype Receptor affinity Receptor affinity Receptor affinity Receptor affinity Receptor affinity Receptor affinity Possible clinical effect
Receptor Subtype Solian olanzapine quetiapine risperidone clozapine haloperidol Possible clinical effect
a-adrenergic receptors a1 a2 - - - - Hypotension, tachycardia, vertigo, sexual dysfunction
serotonin 5HT2A 5HT2C - - - Sedation, weight gain
mAch M1-M2 - - - - Anticholinergic effects, cognitive deficit
histamine H1 - - Sedation, weight gain
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
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Efficacy
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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
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Efficacy positive symptomsEffect size versus
conventional antipsychotics
meta-analysis of 18 randomised controlled trials,
schizophrenic patients Leucht S et al. Am J
Psychiatry 2002
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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
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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
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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
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Efficacy negative symptomsEffect size versus
conventional antipsychotics
meta-analysis of 18 randomised controlled trials,
schizophrenic patients Leucht S et al. Am J
Psychiatry 2002
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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
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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
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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
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Tolerability
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Low EPS profile (AIMS)
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High atypicality effectiveness with minimal
EPSSolians fast off-rate from the
D2-receptorTime needed for 50 release from
cloned D2-receptors1
an effective attenuation of the tonic dopamine
transmission -gt antipsychotic efficacy
with less distortion of the bursts of the
phasic physiological signalling2 -gt 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
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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
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Clinically relevant weight gain versus
risperidone and olanzapine
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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
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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
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Pharmaco-economics
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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
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Posology instructions
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Solian easy to start
easy to switch to
Without titration, immediately at therapeutic
dose

• -gt start Solian
• at the therapeutic dose required
• - without titration

• -gt 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
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Solian easy to useClear dosing1
Acute exacerbations Productive states Stabilisati
on 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
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Pharmacokinetics Drug/drug interactions
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Solian is not metabolized via the CYP450 system
Gillet et al. Neuropsychopharm 10/2000,S331-S332
Package Inserts
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Solian is not metabolized via the CYP450 system
(continued)
Gillet et al. Neuropsychopharm 10/2000,S331-S332
Package Inserts
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• 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

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• 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

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