RATIONALESchizophrenia is a chronic, severe and disabling mental disorder. The disorder is characterized by a variety of clinical manifestati ons, including symptoms that are both positi ve and negati ve, reduced social functi on and community parti cipati on, and cogniti ve impairment. Medicati on nonadherence rates are high in schizophrenia, as they are in many chronic medical conditi ons. Currently there is a dearth of long-term data comparing the use and eff ecti veness of depot and oral anti psychoti cs aft er fi rst-episode psychosis.

AIM OF THE STUDY1) To evaluate the disconti nuati on of the initi al anti psychoti c treatment aft er the fi rst hospital episode of schizophrenia, and2) To compare the risk of rehospitalisati on due to schizophrenia between diff erent anti psychoti cs aft er the fi rst hospital episode of schizophrenia

in a nati onwide cohort of 2,588 pati ents hospitalized for the fi rst ti me with schizophrenia during 2000-2007 in Finland [1].

METHODSThe study was conducted as a register-based case linkage study uti lizing data on hospitalizati on, mortality and anti psychoti c prescripti ons. Hazard rati os (HR) with 95% confi dence intervals (CI) were calculated adjusti ng for the eff ects of sociodemographic and clinical variables, the temporal sequence of the anti psychoti cs used, and the choice of the initi al anti psychoti c.

The primary outcome measures were:1) all-cause disconti nuati on of the initi al anti psychoti c

medicati on,2) rehospitalizati on due to schizophrenia, and3) death from any cause.

ACKNOWLEDGEMENTS• The study was supported by the Annual EVO Financing (special

government subsidies from the Ministry of Health and Welfare, Finland) and by Janssen-Cilag.

• The funders were not involved in the conduct of the study or in the collecti on, management, analysis, or interpretati on of the data.

• The research permission numbers to use the data were obtained from • the Social Insurance Insti tute (Kela 14/522/2009) • the Nati onal Insti tute for Health and Welfare (Dnro 206/5.05.00/2009)• Stati sti cs Finland (TK-53-739-09)

Figure 5. Pairwise comparison depot vs. oral:

Risk of all-cause discontinuation of initial medicaltion

Figure 6. Pairwise comparison depot vs. oral:

Risk of risk of hospitalization

Figure 4. Risk of rehospitalization

Figure 3. Risk of all-cause discontinuation of initial medicaltion

Pasi Korhonen1,2, Jari Haukka2,3,4, Mark Taylor5, Peter M. Haddad6,7, Maxine X. Patel8, Jari Tiihonen9,10

1StatFinn Oy, Espoo, Finland; 2EPID Research Oy, Espoo, Finland; 3Department of Mental Health and Alcohol Research, National Institute for Health and Welfare, Helsinki; 4Tampere School of Public Health, University of Tampere, Finland; 5NHS Lothian, Edinburgh, U.K.; 6Greater Manchester West Mental Health NHS Foundation Trust, Salford, U.K.;

7University of Manchester, Manchester, U.K.; 8Department of Psychosis Studies, Institute of Psychiatry, King’s College London; 9Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; 10Department of Clinical Physiology, Kuopio University Hospital, Kuopio

Schizoaffectivedisorders

ICD-10 F25Npatients = 452

(6.1%)

Longer illness cohortICD-10 F20-F25

Npatients = 25 884 (78%)

Naïve cohortICD-10 F20-F25

Npatients = 7 434 (22%)

Hospitalizations in 2000-2007Diagnosis ICD-10 codes F20-F25

Npatients = 33 318Nhospitalizations = 122 193

SchizophreniaICD-10 F20

Npatients = 2588

(34.8%)

Definition of the naïvecohort• No prior hospitalization

with F20 – F25diagnoses

• No antipsycotics usewithin 6 months prior tothe first hospitalization

Study population:• 16-65 years of age, mean age 37.5 years• 62% male, 38% female

Induceddelusionaldisorder

ICD-10 F24Npatients = 11

(0.1%)

Acute andtransientpsychoticdisorders

ICD-10 F23Npatients = 2689

(36.2%)

Persistentdelusionaldisorder

ICD-10 F22Npatients = 1363

(18.3%)

Schizotypaldisorder

ICD-20 F21Npatients = 331

(4.5%)

2000 2007

Prescription registerDrug substance (ATC)Date of purchaseAmount (DDD)VNR-code (package code)

Cause of death registerCauses of death (ICD10)Date of death

Hospital care registerDiagnosis (ICD10)Start and discharge dateAge, sexHospital & hospital district

doireppu-wolloFyrotsiH

Patient level information

DATA SOURCES

STUDY POPULATION

Figure 2. Descripti on of the study populati on

Figure 1. Linkage of pati ent level data on hospitalizati ons, anti psychoti c prescripti ons and mortality

RESULTS

Pairwise comparison of depot vs. oral formulati ons

Figure 5. Risk of disconti nuati on of initi al

medicati on

Figure 6. Risk of rehospitalizati on

In pooled analysis the depot anti psychoti cs were associated with a 59% lower risk of disconti nuati on (HR=0.41; 95% CI 0.27-0.61; p<0.0001) and with a 64% lower risk of rehospitalizati on (HR=0.36; 95% CI 0.17-0.75; p=0.007) than their respecti ve oral formulati ons.

ABSTRACTObjecti ve: To compare the risk of rehospitali zati on and disconti nuati on of initi al treatment between diff erent anti psychoti cs aft er fi rst hospital episode of schizophrenia.

Methods: A register-based linkage study uti lizing data on hospitalizati ons, mortality, and anti psychoti c prescripti ons in a cohort of 2588 pati ents hospitalized for the fi rst ti me due to schizophrenia in Finland between 2000 and 2007. Adjusted hazard rati os with 95% confi dence intervals (CI) were calculated.

Results: About 58% of pati ents collected a prescripti on for an anti psychoti c within 30 days aft er discharge from hospital and 46% conti nued their initi al treatment for at least 30 days. Among oral anti psychoti cs, clozapine and olanzapine were associated with more favourable outcomes. Depot injecti ons were associated with a 59% (95% CI 39%-73%) lower risk for treatment disconti nuati on and a 64% (95% CI 25%-83%) lower risk for rehospitalisati on than their oral equivalents. Use of any anti psychoti c vs. no anti psychoti c was associated with a 55% (95% CI 33%-69%) lower mortality.

Conclusions: Adherence to the initi al anti psychoti c treatment aft er hospitalisati on is low. Use of depot anti psychoti cs was associated with a signifi cantly lower risk of treatment disconti nuati on and rehospitalizati on than use of oral formulati ons of the same compounds. Use of any anti psychoti c was associated with lower mortality.

Key words: register-based study, schizophrenia, anti psychoti cs, delayed acti on preparati ons, eff ecti veness

REHOSPITALIZATION RISK AND DISCONTINUATION OF INITIAL ANTIPSYCHOTIC TREATMENT AFTER FIRST

HOSPITAL EPISODE OF SCHIZOPHRENIA

CONCLUSIONS• The fi rst study of the adherence and comparati ve

eff ecti veness of specifi c anti psychoti c treatments in a large unselected populati on of pati ents in a real-world setti ng.

• The fi ndings are not att ributable to selecti on bias since the study populati on included all pati ents in Finland with a fi rst hospitalizati on for schizophrenia. Also we adjusted for a number of clinical and sociodemographic factors in the analyses and made a further adjustment by using the choice of the initi al anti psychoti c, refl ecti ng the pati ent’s clinical status at baseline.

• Only a minority of pati ents were adherent to their initi al anti psychoti c during the fi rst 60 days aft er discharge from their fi rst hospitalizati on for schizophrenia.

• The observed higher disconti nuati on rates in our study in comparison with randomized controlled trials, the CATIE and EUFEST studies [2-4], may be partly explained by pati ents in real-life setti ng being less moti vated or co-operati ve because routi ne clinical care and follow-up are less intensive than in randomized controlled trials.

• Oral clozapine and olanzapine were associated with more favorable outcomes regarding all-cause treatment disconti nuati on and rehospitalizati on, similarly as in the CATIE and EUFEST studies [2-4].

• Depot injecti ons were associated with lower risk of treatment disconti nuati on and rehospitalizati on than their equivalent oral formulati ons. A systemati c meta-analysis of randomized controlled trials [5] did not fi nd such a diff erence which may be explained by selecti on because nonadherent pati ents cannot be forced to parti cipate in randomized trials, observati onal studies are the only way to investi gate this issue.

• Because there is no compulsory outpati ent treatment in Finland, our results on the comparati ve eff ecti veness of specifi c anti psychoti cs can be generalized only to pati ents who are willing to use anti psychoti c treatment in outpati ent care.

Figure 3. Risk of all-cause disconti nuati on of initi al anti -psychoti c treatment started within 30 days of discharge aft er the index hospital episode (N=1,507)*Of 2,588 pati ents with a fi rst hospitalizati on• 1,507 (58.2%) started using anti psychoti c medicati on during

the fi rst 30 days aft er discharge.• 1,182 (45.7% of total) conti nued using the initi al

anti psychoti c medicati on for 30 days and longer.• During a mean follow-up period of 2 years 1,394 pati ents

(53.9%) disconti nued their initi al anti psychoti c. • Reasons for disconti nuati ons were 50.6% (n=705) because

of a change in anti psychoti c prescripti on, 34.3% (n=478) because of disconti nuati on, 14.8% (n=207) because of hospitalizati on, and 0.3% (n=4) because of death.

*)The hazard rati os are adjusted by using age at diagnosis, sex, length of fi rst hospital episode, and current and previous use of anxiolyti cs, hypnoti cs and sedati ves, anti depressants, drugs used in addicti ve disorders, analgesics, anti -parkinsonian drugs, blood glucose-lowering drugs, and lipid-modifying agents as covariates.

Figure 4. Risk of rehospitalizati on by anti psychoti c treatment (N=2,588)**• During a mean follow-up period of 2 years, 1,496 pati ents

(57.8%) were rehospitalized because of relapse of schizophrenia symptoms.

• The use of any anti psychoti c was associated with a 62% (95% CI 57%-66%) lower risk when compared to no treatment at all.

• Among oral anti psychoti cs, compared with risperidone, clozapine (HR=0.48; 95% CI 0.31-0.76) and olanzapine (HR=0.54; 95% CI 0.40-0.73) were each associated with a lower rehospitalizati on risk.

**)The hazard rati os are adjusted by using age at diagnosis, sex, length of fi rst hospital episode, previous use of anti -psychoti cs during the follow-up, the choice of initi al anti psychoti c, current and previous use of anxiolyti cs, hypnoti cs and sedati ves, anti depressants, drugs used in addicti ve disorders, analgesics, anti -parkinsonian drugs, blood glucose-lowering drugs, and lipid-modifying agents as covariates.

Risk of all-cause death• During the follow-up period 160 (6.2%) pati ents died. • The use of any anti psychoti c compared with no anti -

psychoti c was associated with a 55% lower mortality (HR=0.45; 95% CI; 0.31-0.67).

1. Tiihonen J et al., Am J Psychiatry (published online March 1, 2011)2. Lieberman JA et al., N Engl J Med 2005; 353:1209-12233. Kahn RS et al., Lancet 2008; 371:1085-10974. McEvoy JP et al., Am J Psychiatry 2006; 163:600-6105. Adams CE et al., Br J Psychiatry 2001; 179:290-299

REFERENCES Contact:Pasi Korhonenpasi.korhonen@epidresearch.comtel. +358 50 365 2990