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9;N°›
![](3D"master103_background.gif")
![](3D"master103_image004.gif")
![](3D"slide0001_image006.gif")
=
Philip Gorwood
CHU Louis Mourier (AP-HP), Paris Diderot
INSERM U675
![](3D"master104_background.gif")
![](3D"master104_image007.gif")
![](3D"master104_image008.gif")
![](3D"slide0002_image010.gif")
=
=
žLes patients sont plus souv=
ent répondeurs au cours du premier épisode <=
/span>que par la suite1
žLes risques de répon=
se
partielle et de rechute sont
néanmoins élevés2,3
žA chaque rechute, la sant&e=
acute;
et le fonctionnement se
déteriorent, le retour au niv=
eau
prémorbide étant rare4
<=
i>1.
Lieberman et al. Neuropsychopharmacology 2003;28:995-1003; 2. <=
/span>Coldham et al. Acta Psychiatr Scand
2002;106:286-290; 3. Breier et al. Am J Psychiatry 1994;151:20-2=
6; 4. Taylor et al. Hum
Psychopharmacol 2005;20:175-181
![](3D"slide0051_image012.gif")
60
![](3D"slide0051_image017.gif")
10
20
30
40
50
=
=
=
=
=
=
=
Bon
Mauvais
=
Age
(années)
Stabilité
Rechut= es
Rechut= es
Lieberman. J Clin Psychiatry 1996;57(Suppl
11):68-71
![](3D"slide0005_image019.gif")
=
•La
reconnaissance des mauvais répondeurs précoces :
<=
/div>
-Adaptation rapide des interventions
thérapeutiques
-Réduire le risque de
co-morbidité (cannabis)
-Réduire le risque d’effe=
ts
indésirables
-Moins de journées
d’hospitalisation
•Une
meilleure compréhension de la physiopathologie du trouble
Emsley et al. Curr O=
pin
Psychiatry 2008;21:173-177
![](3D"slide0006_image021.gif")
=
•Sont associés à une mau=
vaise
réponse précoce
au traitement:
-Longue latence entre émergence du trouble et début des soins (DUP)
•Néanmoins, aucun de ces
critères ne sont suffisamment puissants pour être utilisables=
en clinique
Robinson et al. Am J Psychiatry
1999;156:544-549
DUP, duration of untreated
psychosis
![](3D"slide0007_image023.gif")
=
=
![](3D"slide0007_image024.gif")
=
;
Emsley et al. Curr O=
pin
Psychiatry 2008;21:173-177
![](3D"slide0008_image026.gif")
Marshall et al. Arch=
Gen
Psychiatry 2005;62:975-983
<=
/span>
Publications orginales
Black et al, 1998
Bottlender et al, 2002
Verdoux et al, 1999
Cohorte totale sur 6 mois (n=3D266)
Tirupati et al, 2004
Malla et al, 2002
Cohorte totale sur 12 mois (n=3D133)
Craig et al, 2000
Verdoux et al, 1999
Cohorte totale sur 24 mois (n=3D206)
Huber et al, 1975
=
Cohorte sur 269 mois (n=3D491)
Odds ratio (95% CI)
19.00 (0.87-413.26)
2.74 (1.48-5.07)
10.00 (2.38-42.01)
3.55 (2.03-6.18)
Definition of remission
Pas de symptôme + >3 sur la PANSS
GAF >62
Variante de la méthode “WHO life
chart”
2.73 (0.48-15.59)
2.76 (0.99-7.67)
2.75 (1.14-6.64)
Variante de la méthode “WHO life
chart”
Items globaux de la SAPS <2
=
1.87 (0.59-5.91)
4.00 (1.25-12.84)
2.72 (1.20-6.17)
2.42 (1.51-3.86)
=
2.42 (1.51-3.86)
Pas de symptôme à l’entretien
Variante de la méthode “WHO life
chart”
Variante de la méthode “WHO life
chart”
![](3D"slide0008_image027.gif")
<=
span
lang=3DEN-US style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;
mso-hansi-font-family:Calibri;font-size:67%;mso-special-format:lastCR;
display:none'>
![](3D"slide0008_image028.gif")
![](3D"slide0008_image029.gif")
=
![](3D"slide0008_image030.gif")
=
=
![](3D"slide0008_image031.gif")
=
![](3D"slide0008_image032.gif")
<=
span
lang=3DEN-US style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;
mso-hansi-font-family:Calibri;font-size:67%;mso-special-format:lastCR;
display:none'>
![](3D"slide0008_image033.gif")
=
=
![](3D"slide0008_image034.gif")
=
![](3D"slide0008_image035.gif")
=
<=
span
lang=3DEN-US style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;
mso-hansi-font-family:Calibri;font-size:67%;mso-special-format:lastCR;
display:none'>
![](3D"slide0008_image036.gif")
![](3D"slide0008_image037.gif")
0.2
<=
/div>
0.5
<=
/div>
1
<=
/div>
2
<=
/div>
5
<=
/div>
10
<=
/div>
100
<=
/div>
1000
<=
/div>
![](3D"slide0009_image039.gif")
=
=
•Il existe bien une corrélation=
entre
DUP et nive=
au de
symptômes résiduels à trois ans (n=3D154; p<0.05)
•Sous-groupe des sujets ayant un bon <=
/span>fonctionnement pré-morbide, ju=
sque
durant l=
217;adolescence
et l’enfance
•La DUP pourrait être pré=
dictive
de la r&e=
acute;ponse
thérapeutique chez les sujets ayant un mode d’entrée moins
larvé (plus réversible)
de schizophrénie
*Assessed using Premorbid
Adjustment Scale for childhood and early adolescence; DUP, duration of
untreated psychosis
Norman et al. Schizo=
phr
Res 2007;95:111-114
<=
/span>
![](3D"slide0050_image040.gif")
=
=
žLongue durée de non-traitement rédui=
t les
chances de réponse
(OR=3D0.86, 95%CI[0.76-0.96]
![](3D"slide0050_image042.gif")
![](3D"slide0050_image044.gif")
![](3D"slide0050_image046.gif")
![](3D"slide0050_image048.gif")
=
=
=
=
=
=
Week 1
![](3D"slide0050_image049.gif")
=
=
=
=
=
=
=
Week 2
![](3D"slide0050_image050.gif")
=
=
=
=
=
=
=
Week 3&4
![](3D"slide0050_image051.gif")
=
=
=
=
=
=
=
=
> Week 4
![](3D"master108_background.gif")
![](3D"master108_image052.gif")
![](3D"master108_image053.gif")
![](3D"slide0011_image055.gif")
=
<=
/b>
![](3D"slide0011_image056.gif")
Mauvais Insight
Mauvaise compliance<=
span
lang=3DEN-US style=3D'font-family:Rockwell;mso-ascii-font-family:Rockwell;
mso-hansi-font-family:Rockwell;color:black;mso-color-index:0;mso-special-f=
ormat:
lastCR;display:none'>
![](3D"slide0011_image057.gif")
Mauvais pronostic
Gorwood P. Eur Neuropsychopharm, 2006; 16: S156-S-162.
Shad et al. Int Rev
Psychiatry 2007;19:437-446
![](3D"slide0011_image058.gif")
?
![](3D"master106_background.gif")
![](3D"master106_image059.gif")
![](3D"master106_image060.gif")
![](3D"slide0053_image062.gif")
![](3D"slide0053_image063.gif")
žParmi les 394 patients stabilis&ea=
cute;s
(en rémission partielle-hors critères), un sur cinq va passer en rémission (selon les
critères d’Andreasen) après 1 an de risperidone
![](3D"slide0053_image064.gif")
![](3D"slide0012_image066.gif")
=
&=
#8211;Ne croient pas avoir une maladie1
•Impact démontré du trai=
tement
et des int=
erventions
psychothérapeutiques2
=
;
•Les aspects de l’insight
corrélés au mauvais pronostic:
&=
#8211;Mauvaise reconnaissance des sympt&oci=
rc;mes3
<=
span
style=3D'font-size:92%'>-Alors
que l’attitude envers les traitements n’est pas =
associée à l’insi=
ght3
1.<=
i>Dam.
Nord J Psychiatry 2006;60:114-120; 2
2.<=
i>.
Buckley et al. <=
i>CNS
Drugs 2007;21:129-141;
3. Drake et al. J Clin Psychiatry 2007;68:81-86
![](3D"slide0013_image068.gif")
![](3D"slide0013_image069.gif")
=
=
ž=
;Etude multi-centrique sur 1 an
=
4=
00
patients avec un premier épisode (115 ont interrompu leur =
traitement malgré l’avis=
des
thérapeutes)
Abus de substance
![](3D"slide0013_image070.gif")
Symptômes
dépressifs
Mauvaise insight
(maladie et traitement)
A été en
rémission
Mauvaise adhérence
Interruption
du traitement
Mauvaise réponse
thérapeutique
Haut niveau
cognitif
![](3D"slide0013_image071.gif")
Perkins et al. J Clin
Psychiatry 2008;69:106-113
p<0.05
=
P<0.10
=
L’adhérence au traitem=
ent
et la réponse se renforce mutuellement
Insight Attitude envers son traite=
ment
![](3D"slide0048_image072.gif")
r=3D0.70
![](3D"slide0048_image073.gif")
r=3D0.09
r=3D0.06
Niveau émotionnel
Soutien
Intrusion
Contacts avec soignants
Première admission&#=
13;
Réaction affective
Information
Cœrcivité
Symptômes
Effets indésirable=
s
Connaissance de
son traitement
Lien avec le
prescripteur
![](3D"slide0048_image074.gif")
r=3D0.38
r=3D0.48
![](3D"slide0048_image075.gif")
![](3D"slide0048_image077.gif")
=
![](3D"slide0048_image078.gif")
![](3D"slide0014_image080.gif")
Semaines de traitement
![](3D"slide0014_image083.gif")
Agid et al. Arch Gen Psychiatry
2003;60:1228-1235
Score total
Symptômes psychotiques
=
;
![](3D"slide0014_image084.gif")
=
=
;
=
;
![](3D"slide0014_image085.gif")
=
;
![](3D"slide0014_image086.gif")
=
=
;
=
;
![](3D"slide0014_image087.gif")
=
;
=
;
=
=
;
=
;
0
2
4
6
8
10
12
14
16
18
1
2
3
4
![](3D"slide0014_image088.gif")
=
;
![](3D"slide0014_image089.gif")
=
;
=
;
![](3D"slide0014_image090.gif")
=
;
![](3D"slide0014_image091.gif")
=
;
=
;
![](3D"slide0014_image092.gif")
=
=
;
=
;
=
;
=
;
0
2
4
6
8
10
12
14
1
2
3
4
![](3D"slide0014_image094.gif")
Semaines de traitement
![](3D"slide0015_image096.gif")
![](3D"slide0015_image098.gif")
![](3D"slide0015_image099.gif")
Oosthuizen et al. J Psychopharmacol
2001;15:251-255.
Semaines de traitement
![](3D"slide0015_image102.gif")
n=3D57
![](3D"slide0016_image104.gif")
=
žLa réponse initiale =
au
traitement est fortement
corrélée à la réponse ultérieure1
ž=
;
žSi pas
d’amélioration dans les 15 premiers
jours, peu de chance de succès à un mois2,=
3
•
ž=
1.<=
i>Breier
et al. Arch Gen Psychiatry 1991;48:239-246; 2
2.<=
i>.
Correll et al. Am J Psychiatry 2003;160:2063-2065;
<=
/div>
3. Leucht et al. J C=
lin
Psychiatry 2007;68:352-360
![](3D"slide0017_image106.gif")
Emsley et al. Schizophr Res 2007;89:129-139
<=
/span>
![](3D"slide0017_image108.gif")
![](3D"slide0017_image109.gif")
n=3D57
Score de la PANSS d=
ans
le temps pour les sujets qui arrivent à rémission et les aut=
res
PANSS, positive and negative
syndrome scale
Reproduced with permission
![](3D"slide0017_image110.gif")
![](3D"slide0017_image112.gif")
![](3D"slide0017_image113.gif")
Semaines&n=
bsp;
(interval de confiance à 95%)
![](3D"slide0018_image115.gif")
=
&#=
158;Les patients non répondeurs à 6 <=
span
style=3D'position:absolute;top:32.0%;left:9.17%;width:85.01%;height:7.25%'=
>semaines:
–
&#=
158;Importance de changer de traitement (ou de forme galénique) en cas de réponse insuffisante (selon l’objectif)
ž=
Emsley et al. J Clin
Psychiatry 2006;67:1707-1712
![](3D"master15_background.gif")
![](3D"master15_image116.gif")
![3Dbrain-scan-2](3D"slide0049_image118.gif")
![3Dbrain-scan-1](3D"slide0049_image120.gif")
![](3D"slide0049_image122.gif")
-5.05
-6.52
-6.00
![](3D"slide0049_image123.gif")
-5.05
-7.60
-6.00
-7.00
Talairach coordinate (axial): Z=3D3
Baseline
![](3D"slide0049_image125.gif")
<=
![endif]>![](3D"slide0049_image126.gif")
Follow-up
Talairach coordinate (axial): Z=3D3
van Haren et al. Biol Psychiatry. 2008 Jan 1;63(1):106-13.
=
![](3D"slide0034_image128.gif")
n=3D58 =
; &n=
bsp;
p=3D.02
![](3D"slide0034_image130.gif")
=
=
=
=
=
=
=
=
=
=
=
=
=
<=
span
lang=3DNL style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;mso-h=
ansi-font-family:
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=
<=
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lang=3DNL style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;mso-h=
ansi-font-family:
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=
=
=
=
=
=
=
0
-0.15
100
200
300
400
500
-0.1
-0.05
0
0.05
Clozapine en mg par jour.an
van Haren et al. Biol Psychiatry. 2008 Jan 1;63(1):106-13.
=
![](3D"slide0035_image131.gif")
n=3D53 =
; &n=
bsp;
p=3D.14
=
=
=
=
=
<=
span
lang=3DNL style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;mso-h=
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=
<=
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=
=
=
=
=
=
=
=
=
=
=
=
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<=
span
lang=3DNL style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;mso-h=
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=
<=
span
lang=3DNL style=3D'font-family:Calibri;mso-ascii-font-family:Calibri;mso-h=
ansi-font-family:
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=
=
=
=
=
-0.15
-0.1
-0.05
0
0.05
0
5
10
15
20
25
Perte de substance g=
rise
selon la dose de Haldol cumulative (mg par jour.an) sur 5 ans
Haldol en mg par jour.an
van Haren et al. Biol Psychiatry. 2008 Jan 1;63(1):106-13.
=
![](3D"slide0052_image133.gif")
Median time to relapse=3D15 wks
N=3D33
Taux de rechute après interruption d’un traitement
antipsychotiques sur 2 ans, pour premier
épisode psychotique.
%
![](3D"slide0052_image134.gif")
=
=
=
=
![](3D"slide0052_image135.gif")
=
=
=
=
![](3D"slide0052_image136.gif")
<=
span
lang=3DEN-US style=3D'mso-special-format:lastCR;display:none'>
=
=
![](3D"slide0052_image137.gif")
=
94%
![](3D"slide0052_image138.gif")
0
10
20
30
40
50
60
70
80
90
100
![](3D"slide0052_image139.gif")
Relchutes
Emsley et al. Schizophr Res 2007;89:129-139
<=
/span>
![](3D"slide0033_image141.gif")
=
=
•De nombreux patients ont une ré=
;ponse
positive au traitement1
•Leur risque de réponse partiel=
le, et
de rechute, est en grande partie due à l’interruption de traite=
ment2,3
•Les études sur les antipsychot=
iques
atypiques montrent qu’ils permettent d’obtenir une rémission st=
able5
•L’interruption d’un trait=
ement
efficace initiallement est associé à un risque majeur de rechute,
même après 2 ans… peut être pas de même pour les dix ans? <=
/span>6
<=
span
style=3D'font-size:66%'>•Cible
privilégiée et probablement optimale pour les =
antipsychotiques atypiques, si possib=
le par
IM retard7,
mais sel=
on quels
mécanismes?
1. Lieberman et al. Neuropsychopharmacology
2003;28:995-1003;
2.
Coldham et al. Acta Psychiatr Scand 2002;106:286-290;
3. Breier et al. Am J
Psychiatry 1994;151:20-26; 4. Emsley et al. J Clin Psychiatry
2006;67:1707-1712;
5. Emsley et al.
Manuscript in preparation; 6. Emsley et al. data on file; 7. Chue &
Emsley. CNS Drugs 2007;21:441-485
31/07/2008
Cliquez pour modifier les styles du texte du masque
Deuxième niveau
Troisième niveau
Quatrième niveau
Cinquième niveau
‹N°›
1
2
1.Marked up
<=
/span>
2.Marked up
<=
/span>
3.Marked up
<=
/span>
4.Abstract marked
up
As shown in this slide, most patients ex=
perience
formal onset of illness acutely in the latter pa=
rt of
adolescence and early adulthood but recover from this first episode
The majority then go on to have one or m=
ore
subsequent episodes, from which some fail to rec=
over
at least to their level of functioning pre-episode
By this process, patients accumulate inc=
reased
levels of morbidity involving residual or persis=
ting
symptoms and decrements in function from the status prior to the last episode
Deterioration process almost always occu=
rs in
early phases of illness - pre-psychotic pe=
riod
and first 5 years after initial episode
Following the pre-psychotic period and f=
irst 5
years after initial episode, illness plateaus an=
d,
although there may be subsequent exacerbations, no continued increase in residual symptoms occurs
Lieberman. J Clin Psychiatry 1996;57(suppl
11):68-71
Copyright req=
uired
- Figure 1&=
#13;
4
5
6
7
Marked up
8
Journal
Ref ID: 1131
Title: Early premorbid adjustment as a moderator of the impact of du=
ration
of untreated psychosis
Authors: Norman,R.M.; Malla,A.K.; Manchanda,R.
Pub Date: 2007/7/10
Web/URL: PM:17628442
Notes: DA - 20070713
IS - 0920-9964 (Print)
LA - ENG
PT - JOURNAL ARTICLE
IS - 0920-9964 (Print)
LA - ENG
PT - JOURNAL ARTICLE
Keywords: Canada; London; Ontario; Patients
Reprint: Not in File
Journal: Schizophr Res.
Abstract: OBJECTIVES: Shorter duration of untreated psychosis (DUP) is =
often correlated with a poorer response to treatment. In this paper=
we
test the hypothesis that the importance of DUP is
moderated by early premorbid adjustment. METHOD: Three
year prospective data were collected for 154 first episode patients. DUP, =
premorbid adjustment and symptoms were assessed at time of
presentation for treatment and symptoms were
reassessed after three years of treatment. RESULTS: DUP
was correlated with level of symptoms at three years only for patients wit=
h better premorbid adjustment in childhood and early adolescenc=
e.
CONCLUSIONS: These results suggest that DUP may =
have
more of an impact on treatment response for thos=
e with
a less pernicious, more reversible form of illness
Address: University of Western Ontario and Prevention and Early Interv=
ention
Program for Psychoses, WMCH Building, 392 South
Street, London, Ontario, Canada N6A 4G5
9
=
;
11
12
Insight as a predictor of=
outcome
While the determinants and
psychopathological status of insight may be unclear, its clinical relevanc=
e in
schizophrenia is irrefut=
able.
Poor insight is common in the illness, and is associated with poor complia=
nce
and poor outcome [1]. St=
udies
have shown that between 50% and 80% of all patients with schizophrenia dis=
play
impaired insight to the =
extent
that they do not believe that they have an illness or disorder [2]* (altho=
ugh
insight was found to be =
good in
a majority of first-episode patients [3]*). Its importance as an outcome pred=
ictor
is underpinned by its po=
tential
to be modified by both pharmacological and psychotherapeutic intervention
[4]**. In an important s=
tudy,
Drake et al [5]** investigated a first-episode cohort (N=3D257) followed u=
p for
18 months. The effect of=
insight
(defined according to a validated scale) on outcome (measured as time to
relapse and readmission =
as well
as level of symptoms and social function) was assessed. Poor insight
significantly predicted =
relapse
and rehospitalisation. The aspect of insight that best related to poor out=
come
was poor recognition of =
symptoms. The authors went on to explore po=
ssible
ways in which poor insight could contribute to poor outcome. The most obvious explanation would be tha=
t poor
insight results in poor medication adherence, with ensuing relapse or incomplete treatment response.
However, although adherence was not directly assessed in this study, certain of their findings
indicate that it might not be the most important factor, insofar as patien=
t attitudes towards medication were not=
found
to be significantly associated with insight.
A systematic review of 88 st=
udies
assessing insight and its impact on outcome reported that those investigat=
ing associations between insight and long=
-term
outcome in schizophrenia have provided inconsistent results. While =
most studies support an association b=
etween
insight and medication adherence during the acute treatment phase, the long-term association rema=
ins
unclear. No link between poor insight, poor treatment adherence and poor outcome has been established. The
authors also highlight an interesting and apparently paradoxical finding <=
/span>that better insight in schizophrenia =
is
associated with higher levels of depression and hopelessness. However, they emphasise that the causal direction of this
relationship is unclear and that results are inconclusive [6]**.
A 2 year prospective study o=
f 254
patients recovering from a first-episode of schizophrenia in which predict=
ors
of antipsychotic medicat=
ion
adherence were investigated, found that subjects who do not believe strong=
ly
in the need for, or bene=
fits of
treatment are more likely to become medication non-adherent. Changing these
beliefs regarding treatm=
ent and
the benefits of antipsychotic medication could improve the chances of
long-term medication adh=
erence
[7]**.
13
Secured (figure 3) - NB this study also in
Olivares’ presentation
14
15
16
Note: SM added ‘data on file’ as paper is
12-week study
17
18
Need copyright -figure 1
19
20
20
21
21
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22
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24
' + ENDSHOW_MESG + '
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