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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 .

1997 missing data Hoencamp.179:300–7 . 1980 prefer oral prefer depot Eastwood. 1995 0 50 100 patients (%) Walburn J et al: Br J Psychiatry 2001.Patients’ preferred route of administration Wistedt. 1997 Jacobsson. 1997 prefer combination no preference Pereira.

.22(5):275-82 . 2007 Sep.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.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.22(5):275-82 .

4.3.4.50:667-3 Walburn J et al: Br J Psych 2001. 11: 203-13 Waddell et al: Br J Psych 2009. Pereira S et al: Acta Psych Scand 1997. 23: 789-96 Heres et al: J Clin Psych 2006. 195:S43-50 5.12:110-18 Olfson M et al: Psych Serv: 1999. coercive. 95: 464-8 Svedberg et al: Int J Ment Health Nurs 2003.Myths vs Facts #1  Patient will not accept • Punishment. 3.5 with comments that they “felt better”. 67: 1948-53 Patel MX et al: Adv Psych Treat 2005.2 It cannot be ignored that patients who have tried LAIs prefer this treatment over oral antipsychotics 1. 2. 7. nothing that 10 of 12 studies report patients’ positive opinions and satisfaction towards LAIs 8  1. Patel MX et al: J Psychopharmacol 2009. 8. challenge to patient autonomy 1.179:300-7 . an intrusive treatment • Reserved for more serious illness • “Problematic Patients” • “Last Resort” • Stigmatizing. 6. have a more “normal life” 6 and find injections “easier to remember” 7  A recent systematic review endorses this position.

The attitude of psychiatrists toward antipsychotic depot/LAI treatment .

are old-fashioned (40%) and stigmatizing (48%) • If only a SGA LAI became available. 2003 Jan. this would change the prescription rates of depot tremendously Patel.. et al. Psychol Med.X.33(1):83-9 . M.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%).

179:290-9 3. Glazer WM et al: J Clin Psych 1992.2. 45: 28-35 .4  A recent meta-analysis failed to find an increased risk of TD 2  1. adding that history of NMS is not a contraindication to use of LAI 1  No indication of increased EPS liability 1. 53:426-33 Adams CE et al: Br J Psych 2001. 2.3. Marder SR et al: Arch Gen Psych 1984. 41:1025-9 Glazer WM: J Clin Psych 1984. 4.Myths vs Facts #2  Increased risk of certain side effects No indication of increased NMS risk in LAI treatment.

Which are the main reasons for not prescribing depot/LAI to patients? .

67(12):1948-53 . 2006 Dec..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.001 N=246 patient needs antipsychotic not available as depot costs of drug Heres et al.67(12):1948-53 . J Clin Psychiatry.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..

. 2006 Dec.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. younger colleagues more often prescribe SGA drugs but report lower depot prescription rates Heres et al.67(12):1948-53 .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. J Clin Psychiatry.

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

2008 Prog Neuro-Psychoph.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. Epub Oct 9th . 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.

The attitude toward depot/LAI treatment Efficacy data of depot/LAI treatment First episode patients (FEP) Conclusion .

2005.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 8 5 3 Relapse requiring rehospitalization Pharmacoeconomics.23 Suppl 1:75-89. .

2010.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. 14: 53–62 .

2010. 14: 53–62 .  Klinik für Psychiatrie und Psychotherapie der Ludwig-MaximiliansUniversitaet Muenchen  Isar-Amper-Klinikum Muenchen-Ost  International Journal of Psychiatry in Clinical Practice. non-interventional study Klinik und Poliklinik für Psychiatrie und Psychotherapie der TU Muenchen.  Bezirkskrankenhaus Augsburg.4 German Psychiatric Sites A retrospective.

1 International Journal of Psychiatry in Clinical Practice.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 51.9 34.3 24.5 31.4 53. 14: 53–62 .5 During RLAI 25.9 70.8 36. 2010.7 61.3 74.

6 6.2 6.6 5.9 7.7 International Journal of Psychiatry in Clinical Practice.2 12. 14: 53–62 .6 3.3 18.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. 2010.5 11.1 During RLAI 2.

Does compliance really improve after a switch to a SGA LAI drug? results from a Californian follow-up study .

Psychiatry (Edgmont). Arch Gen Psychiatry.56(3):241–247. 1999.62(7):545–561. 5(6): 43–49.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. 2008 June. 2001. .

5(6): 43–49.Missed scheduled appointments pre-SGA LAI versus post-SGA LAI treatment Psychiatry (Edgmont). 2008 June. .

mean 40 months) .RLAI in the long-run Naturalistic follow-up data from Canada (mirror-image.

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. 2007. Journal of Medical Economics 2007.3 0 at least one hospitalization >1 hospitalizations Beauclaire et al. 10: 427–442 .7 4.7 n=69 21.

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

0 patients without relapse 0. Poster presented at Annual Meeting of the APA 810 .2 0.4 Risperidon LAI 0.Relapse Rates oral quetiapine versus risperidone LAI 1. oral quetiapine (n=337) Medori et al.7 0.9 0.6 0.0 0 90 180 270 360 450 540 630 720 days Risperidone LAI (n=329).1 Log-rank test: p < 0. 2008.3 0.5 Quetiapin oral 0.8 0.0001 0.

002 Favours treatment Favours control Mentschel et al.89 (0.48.99) Schooler 1973 26/107 35/107 0.78 (0.06.36 (0. 4.80 (0.95) Hogarty 1979 22/55 32/50 0.74 (0.65.89) 0.35.92) Quitkin 1978 5/29 Rifkin 1977 1/19 4/24 0.63 (0. 3.92 (0.16 (0. 1. 2003 Presented at: 156th meeting of the American Psychiatric Association .21. 3.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. 0.91) Overall effect.74.85) Falloon 1978 8/20 5/24 1. z=3.48) Del Guidice 1975 21/27 59/61 0.45) Crawford 1974 2/14 6/15 0.66.06 P=0. 0.09.62 (0.14) 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. 1. 6.43. 0.

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? .

co-morbid illness progression.Myths vs Facts #3  NOT recommended for first-episode Schizophrenia Early & effective treatment: favorably alters outcomes & can be associated with decreased suicide attempts. 2.4  Relapse & recurrence in 1st episode patients are strongly associated with antipsychotic nonadherence 5.67(Suppl5):9-14 .50:667-3 Sokal J et al: J Nerv Ment Dis 2004. homelessness & functional deterioration 1. making LAIs an attractive option even at the earliest stages of treatment 8  1.21:419-29 Lieberman JA et al: J Clin Psychopharmacol 1998. 60(suppl 23): 5-9 Kane B et al: J Clin Psych 2006.53:1067-9 Kasper S: J Clin Psych 1999. 8. 7. Weiden PJ et al: Schiz Bull 1995.6. 192: 421-7 5. 4.106:286-90 Edwards J et al: Psych Serv 2002.2. Coldham EL et al: Acta Psych Scand 2002.18:20S-24S Olfson M et al: Psych Serv 1999. repeated hospitalization. 6.3. 3.7.

in press . „life-goal focused“) • 73% of patients randomised on SGA LAI accepted their assignment and started treatment Weiden et al. 2009. J Clin Psychiatry.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.

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. 2009.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. in press .

FEP Results from a 2-year trial from South Africa .

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 Clinical Therapeutics 30(12):2378-86 *Andreasen et al. 23(6):325-31 ¥ Emsley et al. 2005 Am J Psychiatry 162:441-449 .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. 2008 Int Clin Psychopharmacol.3% under risperidone LAI (versus 42.

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 .

why do we have to wait until the first relapse? .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 .