Post on 16-Feb-2016
description
Leonardi A. Goenawan
Efficacy data of depot/LAI treatment
The attitude toward depot/LAI treatment
First episode patients (FEP)
Conclusion
“The gap between knowing and doing”
-
Depot/LAI use worldwide
in the last two decades
-1990 ´91-´93 ´94-´96 ´97-´99 ´00-´02 ´03-´05 ´06-´08
40%
20%
0%
Depot/LAI use worldwidechange in prescription rates over 20 years
The attitude of patients toward
antipsychotic depot/LAI treatment
Walburn J et al: Br J Psychiatry 2001;179:300–7
Wistedt, 1997
Jacobsson, 1980
Eastwood, 1997
Pereira, 1997
Hoencamp, 1995
prefer oral
prefer depot
prefer combination
no preference
missing data
0 50 100
patients (%)
Patients’ preferred route of administration
all participants (n=300)
never been treated with a
depot/LAI formulation before
(depot/LAI naive)
(n=145)
Depot/LAI experienced
patients (n=155)
current
Depot/LAI
treatment
(n=60)
previous
Depot/LAI
treatment
(n=95)
Patients’ experience with depot/LAI treatment
Heres et al., Int Clin Psychopharmacol. 2007 Sep;22(5):275-82
• Acceptance of long-acting injectable antipsychotic
treatment rises with depot/LAI experience
(40% overall acceptance rate)
• Subjective perception of benefits from depot/LAI treatment
rises with depot/LAI experience (previous or ongoing)
• Most often stated subjective reasons for depot/LAI choice
were “reliable effectiveness” and “convenience”
• 95% of patients currently treated with depot/LAI had a
history of schizophrenia longer than three years
Attitude of patients towards
antipsychotic depot/LAI treatment
Heres et al., Int Clin Psychopharmacol. 2007 Sep;22(5):275-82
Myths vs Facts #1
Patient will not accept
1. Patel MX et al: J Psychopharmacol 2009; 23: 789-96
2. Heres et al: J Clin Psych 2006; 67: 1948-53
3. Patel MX et al: Adv Psych Treat 2005; 11: 203-13
4. Waddell et al: Br J Psych 2009; 195:S43-50
5. Pereira S et al: Acta Psych Scand 1997; 95: 464-8
6. Svedberg et al: Int J Ment Health Nurs 2003;12:110-18
7. Olfson M et al: Psych Serv: 1999;50:667-3
8. Walburn J et al: Br J Psych 2001;179:300-7
• Punishment, an intrusive
treatment
• Reserved for more serious illness
• “Problematic Patients”
• “Last Resort”
• Stigmatizing, coercive, challenge
to patient autonomy 1,2
It cannot be ignored that patients who havetried LAIs prefer this treatment over oral antipsychotics 1,3,4,5 with comments that they “felt better”, have a more “normal life” 6 and find injections “easier to remember” 7
A recent systematic review endorses this position, nothing that 10 of 12 studies report patients’ positive opinions and satisfaction towards LAIs 8
The attitude of psychiatrists toward
antipsychotic depot/LAI treatment
Attitude of psychiatrists toward antipsychotic
depot treatment
• Depot antipsychotics are equally effective in the
treatment of schizophrenia (91%), but are less
acceptable for patients (69%) and their relatives (66%)
• Depot antipsychotics have more side effects than their
oral counterparts (38%), are old-fashioned (40%) and
stigmatizing (48%)
• If only a SGA LAI became available, this would change
the prescription rates of depot tremendously
Patel, M.X. et al., Psychol Med. 2003 Jan;33(1):83-9
Myths vs Facts #2
Increased risk of certain side effects
No indication of increased NMS risk in LAI
treatment, adding that history of NMS is not
a contraindication to use of LAI 1
No indication of increased EPS liability 1,2,3,4
A recent meta-analysis failed to find an
increased risk of TD 2
1. Glazer WM et al: J Clin Psych 1992; 53:426-33
2. Adams CE et al: Br J Psych 2001; 179:290-9
3. Marder SR et al: Arch Gen Psych 1984; 41:1025-9
4. Glazer WM: J Clin Psych 1984; 45: 28-35
Which are the main reasons
for not prescribing depot/LAI to patients?
p < 0.001
N=246
per
cent
0
10
20
30
40
50
60
70
80
90
100
sufficient
compliance with
oral drug
depot
recommended but
patient refused
no depot in first
episode patients
poorer control of
effect compared
to oral drug
not appropriate
treatment option
after relapse
FGA
SGA
Statements equally relevant in the decision
against a FGA and SGA depot/LAI drug
Heres et al., J Clin Psychiatry. 2006 Dec;67(12):1948-53
p < 0.001
N=246
0
10
20
30
40
50
60
70
80
90
100
high EPS risk patient needs antipsychotic
not available as depot
costs of drug
FGA
SGA
per
cen
tStatements in the decision against a depot drug
Differences between FGA and SGA depots
Heres et al., J Clin Psychiatry. 2006 Dec;67(12):1948-53
• The main reason for not prescribing depot/LAI was
“good compliance with oral antipsychotic treatment”
• Only 35.5% of all patients suffering from schizophrenia
have ever been offered antipsychotic depot/LAI
treatment
• Psychiatrists who are 50+ years offer and prescribe
depot more often but make less use of SGA drugs;
younger colleagues more often prescribe SGA drugs
but report lower depot prescription rates
Heres et al., J Clin Psychiatry. 2006 Dec;67(12):1948-53
The attitude toward depot/LAI treatment
(German psychiatrists)
Who is considered
to be a candidate
for depot/LAI treatment ?
• Relapses and non-compliance in the past were
considered most strongly designating patients for
antipsychotic depot treatment apart from
archaic/conservative depot/LAI domains like suicidal
risk or hazard risk for others [cluster A]
• High levels of insight, education as well as information
along with openness for drug treatment represent a
cluster of characteristics considered as both relevant
and overall pro-depot/LAI but partly diversely
discussed [cluster B]
• First episode patients are rarely considered as
qualifying for depot/LAI treatment
Who is considered to be
a candidate for depot/LAI treatment?
Heres et al. 2008 Prog Neuro-Psychoph, Epub Oct 9th
Efficacy data of depot/LAI treatment
The attitude toward depot/LAI treatment
First episode patients (FEP)
Conclusion
Cost effectiveness:RLAI vs alternative antipsychotic agents in patients with
schizophrenia (> 1 year - USA)
HLP Depot 2nd gen oral AP RLAI
Relapse requiring
rehospitalization60% 41% 24%
Mean number of days
of relapse requiring
hospitalization per
patient per year
28 18 11
Mean number of days
of exacerbation not
requiring
hospitalization
8 5 3
Pharmacoeconomics.2005;23 Suppl 1:75-89.
• Hospitalization rates
• Duration of inpatient treatment
• Overall treatment costs
18 months
LAI treatment
18 months
pre-LAI treatment
Start of LAI treatment
How “mirror-image” studies work
International Journal of Psychiatry in Clinical Practice, 2010; 14: 53–62
4 German Psychiatric SitesA retrospective, non-interventional study
Klinik und Poliklinik für Psychiatrie und
Psychotherapie der TU Muenchen,
Bezirkskrankenhaus Augsburg,
Klinik für Psychiatrie und
Psychotherapie der Ludwig-Maximilians-
Universitaet Muenchen
Isar-Amper-Klinikum Muenchen-Ost
International Journal of Psychiatry in Clinical Practice, 2010; 14: 53–62
Before vs During RLAI (mean values)Inpatient
6 mo
(N=79)
9 mo
(N=59)
12 mo
(N=50)
15 mo
(N=40)
18 mo
(N=36)
Pre RLAI 51.4 53.7 61.9 70.3 74.5
During RLAI 25.3 24.9 34.5 31.8 36.1
International Journal of Psychiatry in Clinical Practice, 2010; 14: 53–62
Before vs During RLAI (mean values)Day-care clinic days
6 mo
(N=79)
9 mo
(N=59)
12 mo
(N=50)
15 mo
(N=40)
18 mo
(N=36)
Pre RLAI 1.6 6.5 11.2 12.3 18.1
During RLAI 2.6 3.6 5.2 6.9 7.7
International Journal of Psychiatry in Clinical Practice, 2010; 14: 53–62
Does compliance really improve after
a switch to a SGA LAI drug?
results from a Californian follow-up study
The Importance of Adherence
Close to 60 percent of individuals with
schizophrenia are non-adherent with
treatment
Poor adherence leads to clinical
deterioration and increased disability &
adds to the burden cost
J Clin Psychiatry. 2001;62(7):545–561.
Arch Gen Psychiatry. 1999;56(3):241–247.
Psychiatry (Edgmont). 2008 June; 5(6): 43–49.
Missed scheduled appointments pre-SGA LAI versus post-SGA LAI treatment
Psychiatry (Edgmont). 2008 June; 5(6): 43–49.
RLAI in the long-run
-
Naturalistic follow-up data from Canada
(mirror-image, mean 40 months)
SGA depot mirror image studymean follow-up duration 40 months
50.7
21.7
4.3 00
102030405060708090
100
at least one
hospitalization
>1 hospitalizations
pre SGA LAI
SGA LAI
Beauclaire et al. 2007, Journal of Medical Economics 2007; 10: 427–442
Pe
rce
nta
ge
of p
atie
nts
ho
sp
ita
lize
d
n=69
Relapse Risk-
Under depot/LAI versus oral antipsychotic treatment
(data from RCTs and meta-analysis)
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
0 90 180 270 360 450 540 630 720 810
days
pati
en
ts w
ith
ou
t re
lap
se
Quetiapin oral
Risperidon LAI
Log-rank test: p < 0.0001
Relapse Rates
oral quetiapine versus risperidone LAI
Medori et al. 2008, Poster presented at Annual Meeting of the APA
Risperidone LAI (n=329), oral quetiapine (n=337)
Favours treatment Favours control
Barnes 1983 3/19 3/17
Falloon 1978 8/20 5/24
Hogarty 1979 22/55 32/50
Quitkin 1978 5/29 4/27
Rifkin 1977 1/19 4/24
Crawford 1974 2/14 6/15
Del Guidice 1975 21/27 59/61
Schooler 1973 26/107 35/107
Total (95%CI) 88/290 146/325
StudyTreatment
n/NControl
n/N
RR
(95% CI Random)
RR
(95%CI Random)
0.89 (0.21, 3.85)
1.92 (0.74, 4.95)
0.62 (0.43, 0.92)
1.16 (0.35, 3.89)
0.63 (0.06, 6.45)
0.36 (0.09, 1.48)
0.80 (0.65, 0.99)
0.74 (0.48, 1.14)
0.78 (0.66, 0.91)
Overall effect, z=3.06 P=0.002
Mentschel et al. 2003 Presented at: 156th meeting of the American Psychiatric Association
Meta-analysis
Depot/LAI versus oral antipsychotic treatment
update 2010 preliminary:
1-year relapse rates
oral treatment ~ 35%
depot treatment ~ 25%
Does the assumption of a difference in relapse
rates have an influence on the choice between
oral and depot/LAI treatment?
8162
36
110
102030405060708090
100
35% vs
35%
35% vs
30%
35% vs
25%
35% vs
20%
Hamann et al. 2009 in press
Pe
rce
nt o
f p
sych
iatr
ists Depot/LAI
Oral
relapse rate per year
(oral versus depot/LAI treatment)
Difference in relapse ratesan its influence on the choice between oral and depot/LAI treatment
Efficacy data of depot/LAI treatment
The attitude toward depot/LAI treatment
First episode patients (FEP)
Conclusion
FEP
-
Is a compliance challenge there
from the very start?
Myths vs Facts #3
NOT recommended for first-episode Schizophrenia
Early & effective treatment: favorably alters outcomes & can be associated with decreased suicide attempts, co-morbid illness progression, repeated hospitalization, homelessness & functional deterioration 1,2,3,4
Relapse & recurrence in 1st episode patients are strongly associated with antipsychotic non-adherence 5,6,7, making LAIs an attractive option even at the earliest stages of treatment 8
1. Weiden PJ et al: Schiz Bull 1995;21:419-29
2. Lieberman JA et al: J Clin Psychopharmacol 1998;18:20S-24S
3. Olfson M et al: Psych Serv 1999;50:667-3
4. Sokal J et al: J Nerv Ment Dis 2004; 192: 421-7
5. Coldham EL et al: Acta Psych Scand 2002;106:286-90
6. Edwards J et al: Psych Serv 2002;53:1067-9
7. Kasper S: J Clin Psych 1999; 60(suppl 23): 5-9
8. Kane B et al: J Clin Psych 2006;67(Suppl5):9-14
• Randomised trial on 37 patients initiated on risperidone oral or
LAI formulation
• Non-compliance defined as medication gap of 14 days under
oral treatment or skipping one injection under LAI treatment
• 2-year study, interim analyses at 12 weeks and 1 year
• All patients favored oral treatment before randomisation
• Brief psychoeducational sessions on antipsychotic treatment
(2 sessions, „life-goal focused“)
• 73% of patients randomised on SGA LAI accepted their
assignment and started treatment
Weiden et al. 2009, J Clin Psychiatry, in press
SGA LAI in first episode patientsinterim data from a 2-year trial on compliance
SGA LAI in first episode patientsnon-compliance in the first 12 weeks of treatment
0102030405060708090
100
risperidone LAI risperidone oral
Weiden et al. 2009, J Clin Psychiatry, in press
% o
f p
atie
nts
be
ing
no
n-c
om
plia
nt
SGA LAI in first episode patientsnon-compliance in the first 12 weeks of treatment
11
39
0102030405060708090
100
risperidone LAI risperidone oral
Weiden et al. 2009, J Clin Psychiatry, in press
% o
f p
atie
nts
be
ing
no
n-c
om
plia
nt
FEP
-
Results from a 2-year trial from South Africa
• Risperidone LAI initiated in 50 first-episode patients
• 72% maintained RLAI treatment till the end of the trial
(75% retention rate in year 1)
• Relapse rate 9.3% under risperidone LAI
(versus 42.1% under oral risperidone or haloperidol¥)
• 64% met criteria for remission in the course of the study
(RSWG criteria*) under risperidone LAI
• 97% of remitted patients maintained remitted till the end of
the trial
Emsley et al. 2008 Int Clin Psychopharmacol. 23(6):325-31¥ Emsley et al. 2008 Clinical Therapeutics 30(12):2378-86
*Andreasen et al. 2005 Am J Psychiatry 162:441-449
SGA LAI in FEPresults from a 2-year trial in South Africa
Is the compliance problem solved now?
-SGA LAI initiation is the „first step“
(but a very important one!)
Efficacy data of depot/LAI treatment
The attitude toward depot/LAI treatment
First episode patients (FEP)
Conclusion
Conclusions
• Depot/LAI therapy is still rather an exceptional approach
than a routine treatment strategy
– despite considerable advantages
• Psychiatrists anticipate a negative attitude of patients
toward depot/LAI treatment - this is not verified in surveys
• FEP are rarely treated with depot/LAI drugs
- despite growing excellent evidence
- why do we have to wait until the first relapse?