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?