332 – RISK FACTORS OF QT INTERVAL PROLONGATION IN1000 PATIENTS WITH SCHIZOPHRENIA

Y. Ozeki1, K. Fujii 2, N. Kurimoto3, K. Tsuji 4, N. Yamada5,M. Okawa5, T. Aoki6, J. Takahashi6, N. Ishida7, M. Narita8,O. Saito3, M. Horie4, H. Kunugi1.

1Department of Mental Disorder Research, National Institute ofNeuroscience, National Center of Neurology and Psychiatry, Tokyo,Japan2Departament of Psychiatry, Dokkyo University School of Medicine,Mibu, Japan3Department of Psychiatry, National Center Hospital for Mental,Nervous and Muscular Disorders, National Center of Neurology andPsychiatry, Tokyo, Japan4Department of Cardiovascular and Respiratory Medicine, ShigaUniversity of Medical Science, Otsu, Japan5Department of Psychiatry, Shiga University of Medical Science,Otsu, Japan6Minakuchi Hospital, Minakuchi, Japan7Biwako Hospital, Otsu, Japan8Toyosato Hospital, Toyosato, Japan

Presenting Author details: yozeki@ncnp.go.jp4-1-1 ogawahigashicyo, 187-8502 Kodaira Tokyo, Japan,Tel.: +81 42 3412711; fax: +81 41 3461744.

Background: Sudden unexpected death occurs almost twice as oftenin populations treated with antipsychotics as in normal populations.Drug-induced QTc interval prolongation of electrocardiogram is oneof a flag that warns the possibility of ventricular arrhythmia andsudden death. However, there are few studies investigating clinicalrisk factors of prolonged QTc in a large sample size especially inAsian countries.Methods: Data of QTc interval, medication, laboratory tests ofblood and general medical condition were collected from medicalrecords in 1024 schizophrenic patients. All patients were admittedto one of four psychiatric hospitals in Japan and diagnosedaccording to the DSM-IV criteria. Individuals with hypo-potassiumor those with hypothyroid patients were excluded from the analysis.We determined that the prolongation of QTc interval being morethan 470 msec1/2 by the Bazett's formula. A logistic regressionanalysis was performed to control for the possible effects of sex,age and duration of illness. Chlorpromazine equivalent dose ofneuroleptics, biperiden equivalent dose of antiparkinsonian drugsand diazepam equivalent dose of benzodiazepines were calculatedfor each patient. Antipsychotics that were administrated more than10% of the patients (i.e., oral administration of haloperidol,chlorpromazine, risperidone, olanzapine, levomepromazine, zotepineand intravenous infusion of haloperidol) were individually enteredinto the model.Results: Chlorpromazine equivalent doses of antipsychotics, intrave-nous infusion of haloperidol and oral administration of chlorpromazinewere significantly associated with an increased risk of QTc prolonga-tion (pb0.001, pb0.001 and pb0.005 respectively). No significanteffects were found for antiparkinsonian drugs or benzodiazepines. Alllogistic models fitted well according to the Hosmer–LemeshowGoodness-of-Fit Test.Conclusions: Monitoring ECG is important for those patientsreceiving an excessive dose of antipsychotics, intravenous infusionof haloperidol and oral administration of chlorpromazine. To elucidate

individual factors, molecular genetic studies on QTc prolongation areunder way.

doi:10.1016/j.schres.2007.12.399

333 – DO ATYPICAL ANTIPSYCHOTICS REALLY HAVE COST/BENEFIT RATIO LESS THAN CONVENTIONALANTIPSYCHOTICS IN LOWER SOCIOECONOMICSCHIZOPHRENICS?

P. Palitponganpim1.

1Department of Psychiatry, Chiangrai Regional Hospital, Chiangrai,Thailand

Presenting Author details: prasertppp@yahoo.comAmphur Muang, 57000 Chiangrai, Thailand,Tel.: +66 81 8852053; fax: +66 53 713044.

Background: In Chiangrai State Hospital of northern Thailand, adeveloping country with agricultural basis, atypical antipsychoticsshould not be considered as the first line drug for treatment ofschizophrenia because most schizophrenic patients' career are farmersor labors with low socioeconomic status. Conventional antipsychoticswith much more lower cost can get the optimal good results formaintaining their lower skilled occupational functions.Methods: Comparing the cost of two atypical antipsychotics(olanzapine and risperidone) to seven typical antipsychotics (chlor-promazine, thioridazine, haloperidol, trifluoperazine, perphenazine,fluphenazine decanoate and haloperidol decanoate) and the outcomesof treatment during the fiscal years 2005, 2006 and 2007. Theoutcomes classified as in partial or complete remission, with or withoutoccupational function.Results: Cost of the two atypical antipsychotics are 570,844,1,013,640 and 1,129,263 baht/year consecutively for treating 13schizophrenics while cost of the seven typical antipsychotics are595,655, 680,444 and 542,855 baht/year consecutively for treating6051 schizophrenics. All of the patients got atypical antipsychotics and84.26% of the patients got typical antipsychotics are in partialremission which can maintain their occupational functions.Conclusions: In the lower socioeconomic schizophrenics who neednot highly skill in occupational functions, typical antipsychoticsshould be considered as the first line drugs rather than atypicalantipsychotics which consume very much more costs.

doi:10.1016/j.schres.2007.12.400

334 – LONG-TERM SAFETY/TOLERABILITY OFPALIPERIDONE EXTENDED-RELEASE TABLETS: 52-WEEK,OPEN-LABEL EXTENSION STUDY

M. Kramer1, G. Simpson2, S. Kushner1, Y. Liu3, P. Lim1,D. Hough1, M. Eerdekens4, J. Palumbo1.

1Johnson & Johnson Pharmaceutical Research and Development,Titusville, NJ, USA

170 ABSTRACTS / Schizophrenia Research 98 (2008) 3–199

2Keck School of Medicine, University of Southern CaliforniaDepartment of Psychiatry, CA, USA3Johnson & Johnson Pharmaceutical Research and Development,Raritan, NJ, USA4Johnson & Johnson Pharmaceutical Research and Development,Beerse, Belgium

Presenting Author details: jpalumbo@prdus.jnj.com1125 Trenton-Harbourton Road, P.O. Box 200, 08560 Titusville,United States,Tel.: +1 609 7306775.

Background: A 52-week, open-label extension (OLE) phase of aplacebo-controlled, double-blind (DB), symptom recurrence preven-tion study in stable schizophrenia patients evaluated the long-termsafety/tolerability of paliperidone extended-release tablets (paliper-idone ER, 3–15 mg/day).Methods: The OLE safety population (N=152) included patients whohad participated in the DB phase (80 had received placebo [PBO/PAL];72 had received paliperidone ER flexible doses [PAL/PAL]) andpatients who were in the DB run-in (RI)/stabilization phase at the timeof DB study termination (n=83; RI/PAL). OLE paliperidone ERtreatment was initiated at 9 mg/day; dose titrations of 3 mg/day werepermitted (maximum=15 mg/day; minimum=3 mg/day). Medianduration of exposure (RI to OLE endpoint)=456 days. OLE meanmodal dose = 11.2 mg/day (PBO/PAL= 10.8 mg/day; PAL/PAL=10.8 mg/day; RI/PAL=11.9 mg/day).Results: Sixty percent of patients completed the OLE; 5% (n=12)discontinued due to treatment-emergent adverse events (TEAEs).TEAEs occurred in 69% of patients (PBO/PAL=63%; PAL/PAL=63%; RI/PAL=82%). The most common TEAEs weretremor (13%; n=31), akathisia (11%; n=25), headache (8%;n=19) and insomnia (8%; n=18). Thirteen patients (6%; allfemale) experienced potentially prolactin-related TEAEs (15% ofevents=amenorrhea). Serious TEAEs were reported in 6% ofpatients (n=13); one patient died during the OLE (convulsion/pulmonary embolism). EPS rating scale median total scores=0 atOLE baseline and endpoint. Cardiovascular, metabolic and weight-related assessments demonstrated clinically minimal changes duringthe OLE. Mean±SD PANSS total score in OLE decreased atendpoint (−8.7±18.4).Conclusions: In this study, long-term exposure to paliperidone ERwas safe and well tolerated, with a safety profile similar to otherpaliperidone ER studies.Acknowledgement: Data previously presented at the AmericanCollege of Neuropsychopharmacology congress, 2007. Supportedwith funding from Johnson & Johnson Pharmaceutical Services, LLC,and Johnson & Johnson Pharmaceutical Research & Development.

doi:10.1016/j.schres.2007.12.401

335 – FIRST AND SECOND GENERATION ANTIPSYCHOTICTHERAPY: OUTCOME AND COMPLIANCE IN A COMMUNITYSAMPLE OF SCHIZOPHRENIC SUBJECTS

L. Pesce1, A. Luoni1, S. Scarone1, O. Gambini1.

1Departement of Psychiatry, San Paolo Hospital, University of Milan,Milan, Italy

Presenting Author details: luisa.pesce@studenti.unimi.itvia A. DI Rudini 8, 20100 MILANO, Italy,Tel.: +39 02 81844730; fax: +39 02 81844026.

Background: Extensive clinical literature points out that second-generation antipsychotics (SGAs) brought relevant improvement in thetreatment of schizophrenia. Nevertheless outcome and compliance ofSGAs compared to the first generation antipsychotic (FGAs) incommunity psychiatry is not yet well established.Methods: We retrospectively compared the outcome and complianceof FGAs to SGAs in 175 subjects with a diagnosis of DSM IV-TRschizophrenia, delusional disorders or NOS psychosis, in charge at theSan Paolo University Hospital inpatient and outpatient facilities duringa 5-year period (march 2002 to march 2007). Antipsychotic class andmolecule, way of administration, number and duration of hospitaliza-tions, therapy changes were checked. Clinical Global ImpressionsScale (CGI) for each patient at the end of the observational period wasperformed.Results: 145 patients completed the 5-year observational period. Nocorrelation among age, sex, onset and pharmacological therapy wasfound. The number of involuntary admission and hospitalizations isnot significantly different among any of the FGAs and SGAs. Theaverage duration of first hospitalization was significantly longer forthose patients treated with SGAs (P=0.001). We observed a betteradherence to therapy for those patients treated with depot haloperidol,olanzapine, risperidone and clozapine. Almost all changes from SGAswere to other SGAs. At the end of the observational period, patients onSGAs had less serious disease (CGI 1); better clinical conditions (CGI2); high efficacy index (CGI 3). No significant difference was foundamong the SGAs. 30 patients were not on charge at the end of the 5-year period: 6 because of death, 21 moved to other cities or facilities, 3refused antipsychotic therapy.Conclusions: SGAs are associated with a significant improvement ofthe disease and a high CGI3 efficacy index. Furthermore they areassociated with a better compliance, particularly risperidone, clozapineand olanzapine. Depot haloperidol was the only FGAwith efficacy andcompliance results similar to those of the SGAs.

doi:10.1016/j.schres.2007.12.402

336 – COMBINATION OF NEW ANTIPSYCHOTICS IN THETREATMENT-RESISTANT SCHIZOPHRENIC, APPROACHESTO THE CONCEPT OF POLYPHARMACY

J. Quintero Gutierrez1,2, A. Chinchilla Moreno3,4, C. Mur De Viu2,J. De Dios Molina5.

1Fundación Jimenez Díaz, Madrid, Spain2Universidad Autónoma de Madrid, Spain3Hospital Ramón y Cajal4Universidad de Alcalá, Madrid, Spain5Hospital Rodriguez Lafora

Presenting Author details: fjquinterog@yahoo.esSegre 7, 28002 Madrid, Spain,Tel.: +34 91 5504917; fax: +34 91 5504987.

Background: Antipsychotic combination therapy in schizophrenia isnowadays widely used, whereas switching antipsychotics was the most

171ABSTRACTS / Schizophrenia Research 98 (2008) 3–199