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Leonardi A.

Goenawan

The attitude toward depot/LAI treatment


Efficacy data of depot/LAI treatment
First episode patients (FEP)
Conclusion

The gap between knowing and doing


Depot/LAI use worldwide
in the last two decades

Depot/LAI use worldwide


change in prescription rates over 20 years

40%
20%
0%
-1990

91-93

94-96

97-99

00-02

03-05

06-08

The attitude of patients toward


antipsychotic depot/LAI treatment

Patients preferred route of administration


Wistedt, 1997

Jacobsson, 1980

prefer oral
prefer depot

Eastwood, 1997

prefer combination
no preference

Pereira, 1997

missing data

Hoencamp, 1995
0

50

100

patients (%)
Walburn J et al: Br J Psychiatry 2001;179:3007

Patients experience with depot/LAI treatment


all participants (n=300)

Depot/LAI experienced
patients (n=155)
never been treated with a
depot/LAI formulation before
(depot/LAI naive)
(n=145)

current
Depot/LAI
treatment
(n=60)

previous
Depot/LAI
treatment
(n=95)

Heres et al., Int Clin Psychopharmacol. 2007 Sep;22(5):275-82

Attitude of patients towards


antipsychotic depot/LAI treatment
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

Heres et al., Int Clin Psychopharmacol. 2007 Sep;22(5):275-82

Myths vs Facts #1

Patient will not accept

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 have


tried 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

1.
2.
3.
4.

Patel MX et al: J Psychopharmacol 2009; 23: 789-96


Heres et al: J Clin Psych 2006; 67: 1948-53
Patel MX et al: Adv Psych Treat 2005; 11: 203-13
Waddell et al: Br J Psych 2009; 195:S43-50

5.
6.
7.
8.

Pereira S et al: Acta Psych Scand 1997; 95: 464-8


Svedberg et al: Int J Ment Health Nurs 2003;12:110-18
Olfson M et al: Psych Serv: 1999;50:667-3
Walburn J et al: Br J Psych 2001;179:300-7

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.
2.

Glazer WM et al: J Clin Psych 1992; 53:426-33


Adams CE et al: Br J Psych 2001; 179:290-9

3.
4.

Marder SR et al: Arch Gen Psych 1984; 41:1025-9


Glazer WM: J Clin Psych 1984; 45: 28-35

Which are the main reasons


for not prescribing depot/LAI to patients?

Statements equally relevant in the decision


against a FGA and SGA depot/LAI drug
100
90
80
70
60
50
40
30
20
10
0

percent

FGA
SGA

p < 0.001
N=246

sufficient
depot
no depot in first
compliance with recommended but episode patients
oral drug
patient refused

poorer control of not appropriate


effect compared treatment option
to oral drug
after relapse

Heres et al., J Clin Psychiatry. 2006 Dec;67(12):1948-53

Statements in the decision against a depot drug

percent

Differences between FGA and SGA depots


100
90
80
70
60
50
40
30
20
10
0

FGA
SGA

high EPS risk

p < 0.001
N=246

patient needs antipsychotic


not available as depot

costs of drug

Heres et al., J Clin Psychiatry. 2006 Dec;67(12):1948-53

The attitude toward depot/LAI treatment


(German psychiatrists)
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

Who is considered
to be a candidate
for depot/LAI treatment ?

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
Heres et al. 2008 Prog Neuro-Psychoph, Epub Oct 9th

The attitude toward depot/LAI treatment


Efficacy data of 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

60%

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

Relapse requiring
rehospitalization

Pharmacoeconomics.2005;23 Suppl 1:75-89.

How mirror-image studies work


Start of LAI treatment
Hospitalization rates
Duration of inpatient treatment
Overall treatment costs

pre-LAI treatment

18 months

LAI treatment

18 months

International Journal of Psychiatry in Clinical Practice, 2010; 14: 5362

4 German Psychiatric Sites


A retrospective, non-interventional study

Klinik und Poliklinik fr Psychiatrie und


Psychotherapie der TU Muenchen,
Bezirkskrankenhaus Augsburg,
Klinik fr Psychiatrie und
Psychotherapie der Ludwig-MaximiliansUniversitaet Muenchen
Isar-Amper-Klinikum Muenchen-Ost

International Journal of Psychiatry in Clinical Practice, 2010; 14: 5362

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: 5362

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: 5362

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):545561.


Arch Gen Psychiatry. 1999;56(3):241247.
Psychiatry (Edgmont). 2008 June; 5(6): 4349.

Missed scheduled appointments


pre-SGA LAI versus post-SGA LAI treatment

Psychiatry (Edgmont). 2008 June; 5(6): 4349.

RLAI in the long-run


Naturalistic follow-up data from Canada
(mirror-image, mean 40 months)

SGA depot mirror image study


Percentage of patients hospitalized

mean follow-up duration 40 months

100
90
80
70
60
50
40
30
20
10
0

pre SGA LAI


SGA LAI
50.7
n=69

21.7
4.3

at least one
hospitalization

>1 hospitalizations

Beauclaire et al. 2007, Journal of Medical Economics 2007; 10: 427442

Relapse Risk
Under depot/LAI versus oral antipsychotic treatment
(data from RCTs and meta-analysis)

Relapse Rates
oral quetiapine versus risperidone LAI
1,0

patients without relapse

0,9
0,8
0,7
0,6
0,5

Quetiapin oral

0,4

Risperidon LAI
0,3
0,2
0,1

Log-rank test: p < 0.0001

0,0
0

90

180

270

360

450

540

630

720

days

Risperidone LAI (n=329), oral quetiapine (n=337)


Medori et al. 2008, Poster presented at Annual Meeting of the APA

810

Meta-analysis
Depot/LAI versus oral antipsychotic treatment
RR
(95% CI Random)

RR
(95%CI Random)

n/N

Control
n/N

Barnes 1983

3/19

3/17

0.89 (0.21, 3.85)

Falloon 1978

8/20

5/24

1.92 (0.74, 4.95)

Hogarty 1979

22/55

32/50

0.62 (0.43, 0.92)

Quitkin 1978

5/29

Rifkin 1977

1/19

4/24

0.63 (0.06, 6.45)

Crawford 1974

2/14

6/15

0.36 (0.09, 1.48)

Del Guidice 1975

21/27

59/61

0.80 (0.65, 0.99)

Schooler 1973

26/107

35/107

0.74 (0.48, 1.14)

Total (95%CI)

88/290

Study

Treatment

update
2010 preliminary:
4/27
1-year relapse rates

oral treatment ~ 35%

146/325
depot
treatment ~ 25%

1.16 (0.35, 3.89)

0.78 (0.66, 0.91)

Overall effect, z=3.06 P=0.002


Favours treatment

Favours control

Mentschel et al. 2003 Presented at: 156th meeting of the American Psychiatric Association

Does the assumption of a difference in relapse


rates have an influence on the choice between
oral and depot/LAI treatment?

Difference in relapse rates

Percent of psychiatrists

an its influence on the choice between oral and depot/LAI treatment

100
90
80
70
60
50
40
30
20
10
0

Depot/LAI
Oral

81
62
36
11
35% vs
35%

35% vs
30%

35% vs
25%

35% vs
20%

relapse rate per year


(oral versus depot/LAI treatment)
Hamann et al. 2009 in press

The attitude toward depot/LAI treatment


Efficacy data of 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 nonadherence 5,6,7, making LAIs an attractive
option even at the earliest stages of treatment 8

1.
2.
3.
4.

Weiden PJ et al: Schiz Bull 1995;21:419-29


Lieberman JA et al: J Clin Psychopharmacol 1998;18:20S-24S
Olfson M et al: Psych Serv 1999;50:667-3
Sokal J et al: J Nerv Ment Dis 2004; 192: 421-7

5.
6.
7.
8.

Coldham EL et al: Acta Psych Scand 2002;106:286-90


Edwards J et al: Psych Serv 2002;53:1067-9
Kasper S: J Clin Psych 1999; 60(suppl 23): 5-9
Kane B et al: J Clin Psych 2006;67(Suppl5):9-14

SGA LAI in first episode patients


interim data from a 2-year trial on compliance
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 patients


% of patients being non-compliant

non-compliance in the first 12 weeks of treatment

100
90
80
70
60
50
40
30
20
10
0
risperidone LAI

risperidone oral

Weiden et al. 2009, J Clin Psychiatry, in press

SGA LAI in first episode patients


% of patients being non-compliant

non-compliance in the first 12 weeks of treatment

100
90
80
70
60
50
40
30
20
10
0

39
11

risperidone LAI

risperidone oral

Weiden et al. 2009, J Clin Psychiatry, in press

FEP
Results from a 2-year trial from South Africa

SGA LAI in FEP


results from a 2-year trial in 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

Is the compliance problem solved now?


SGA LAI initiation is the first step
(but a very important one!)

The attitude toward depot/LAI treatment


Efficacy data of 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?

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