P.3 Psychotic disorders and anti psychotics S4-115 I P.3.040 I Olanzapine versus haloperidol: Results of the international trial P.V.Tran, M.A.Deliva. R. Tamura, J. Krueger, C.M. Beasley, G.D. Tollefson. The Olanzapine D evelopment Team, Lilly Research Laboratories, lilly Corporate Center, DC 0538 Indianapolis IN 46285 This double-blind, 6 week, parallel, multinational trial comparedthe efficacy and safety of a dose rangeof olanzapine ( 5-20 mg/day) to a dose range of haloperidol(5-20 mg/day), in 1,996patients meetingDSMIll-R criteria for schizophrenia (83.1%), schizophreniform disorder (1.9%), or schizoaffective disorder (15.0%). A statisticallysignificantly (p < 0.00I) greaterproportion of olanzapine- treated patients (66.4%) completed the 6-week acute phase than haloperidol-treated patients (46.8%). The proportions of olanzapine- treatedpatientsdiscontinuing for lackof efficacy and adverseeventswere also statistically significantly smaller compared with haloperidol-treated patients. On the primary analysisof overall efficacy, the difference in baselineto endpoint(LOCF) mean change on the BPRS, olanzapinewas statistically significantly superior to haloperidol (-10.89. -7.93. P = 0.015). Mean change on CGI-S and response rate (> 40% improvement on BPRS with 3 or more weeks of treatment) significantly favored olanzapine as did improvement on BPRS-negative and PANSS-negative. There was statisticallysignificantly less treatmentemergentdystonia. parkinsonism. andakathisiawitholanzapinethan withhaloperidol. Scores on Simpson Angus. Barnes,and AIMS decreased for olanzapine-treated patientsand were statisticallysignificantly superior to haloperidol. The result of this largeclinical trial indicated that olanzapine offered superior efficacy in the treatmentof psychotic and negative symptomatol- ogy and a better risklbenefit ratio over the conventional neuroleptic agent haloperidol. References [1) Beasley Jr CM. TOllefson GO, Tran P. S atterlee W. Sanger T. Hamilton S. The Olanzapine HGAD Smdy Group (199 6): Ol anzapine versus placebo and haloperidol : acute phase results of theN orth American double-blind olanzapine trial. Neuropsycbophannacol 14(2): 105-11 8 (2) Tran PV , Be asley CM, Tollef son GO. Crawford AM, Paul S: Olanzapine: An update on recent clinical studies. New Cli nical Drug E valuation Unit, 35th Annual Meeting. Orlando, florida. June I, 1995 IP.3.041 I Acute phase efficacy and safety of olanzapine: A review A. Kuntz,P.Tran, M.A. Deliva, T. Sanger, C. Beasley, G.D. Tollefson. TheOlanzapine Development Team, Lilly Research Laboratories, Lilly Corporate Center, DC 0538, Indianapo lis IN 46285 Olanzapineis a promisingnew novel antipsychotic agent with a pharma- cological profile similar to clozapine, the prototype "atypical" antipsy- chotic. There havebeen four large, double-blind, multicenter, randomized trials comparing multiple fixed dose-ranges of olanzapine with either placebo or haloperidol. TIle four trials enrolleda total of 2,914 patients with a diagnosisof schizophrenia, schizophreniform disorderor schizoaf- fective disorder according to DSMIII-R. With regard to efficacy, in 3 of the 4 trials, the olanzapine treatment groups who received clinically effective doses of olanzapine were statistically significantly superior to placebo and/or haloperidol in BPRS total, PANSS negative or SANS negative, CGI-S, and MADRS(when included). Withrespect to pooled safetyresults,the proportions of patients whodiscontinued for an adverse event were low and were comparable between the olanzapine (4.8%) and the placebo (5.9%) groups. In contrast, a statistically significantly greater proportion of patients in the haloperidol group (8.1%) than in the olanzapine group (5.5%) discontinued for adverse events. Among treatment-emergent adverse events, somnolence, dizziness, weight gain, and akathisia were reported statistically significantly more frequently in olanzapine-treated than in placebo-treated patients. In contrast, paranoid reaction, anorexia, flu syndrome, delusions, and weight loss were re- ported statistically significantly more frequently in placebo-treated than in olanzapine-treated patients. When comparing the olanzapine with the haloperidol treatment group, the most commonly reported (::: 10% incidence) treatment-emergent adverse events in the olanzapine group were somnolence, headache and insomnia where as events indicative of extrapyramidal side effects (akathisia, hypertonia, tremor) and ner- vousness,somnolence, insomniaand headache were reported most often by the haloperidol group. The olanzapinegroup reported statistically significantly more dry mouth, weight gain, increasedappetite, SGFT increased, cough increased, tachycardia, liverfunction test abnormal,and peripheral edemathan the haloperidol group. In contrast, the incidenceof nervousness. anxiety, akathisia,hypertonia, tremor,vomiting,amblyopia, extrapyramidal syndrome, increased salivation, joint disorder, anorexia, nausea, vomiting, weight loss, cogwheel rigidity, hypokinesia, dyskine- sia, dystonia,oculogyriccrisis, chills, abnormalgait, hiccup, and tongue disorder was statistically significantly greater in the haloperidol group. The majority of these events were reflective of extrapyramidal symp- tomatology. Moreover, haloperidol-treated patients (67.5%) exhibited a statisticallysignificantly greaterincidenceofhigh prolactinconcentration than olanzapine-treated patients(33.9%). We conclude that olanzapine was effective in treating a broad range of symptomatology including positive, negative and mood symptoms. Over- all, olanzapinewas well tolerated and had a low EPSliability comparable to placebo. Olanzapine had a superiorrisklbenefitratio compared to the conventional neuroleptic agent haloperidol and these results suggest that olanzapine is a very promisingnew antipsychotic agent. References [l] B easley Jr CM, Tollefson GO. Tran P, Satterlee W, Sanger T, Hamilton S, The Olanzapine HGAD Study Group (1996): Olanzapine versus placebo and haloperidol: a cute phase results oftheNorth American double-blind olanzapine trial. Neuropsychopharmacol 14(2) : t05-1t8 (2) Bymaster FP, Call igaro DO, Falcone JF, Marsh RD. Moore NA, Tye NC, Seeman P, Wong DT (1996): Radioreceptor binding profite of the atypical antips ychotic olanzapine. Neuropsychopharmacol 14(2): 87-96 I P.3.042 ! Long-term continuation therapy with the novel antipsychotic olanzaplne: A review of the clinical experience P.V. Tran, M.A. Deliva, V. Rampey. G.D. Tollefson, C.M. Beasley. The Olanzapine Development Team, Lilly Research Laboratories, Lilly Corporate Center, DC 0538, Indianapolis IN 46285 The efficacy of olanzapine, a promising novel antipsychotic agent, in acute treatmentof schizophrenia and relateddisorders has been reported previously. In this report, we show the efficacy results in maintenance treatment of 3 fixed dose-ranges of olanzapine [Olz-L, 5.0 ± 2.5 mg: Olz-M, 10.0 ± 2.5 mg: Olz-H, 15.0 ± 2.5 mg] compared to placebo (study HGAD), a presumed ineffective dose of olanzapine of I mg (study E003) and haloperidol (studyHGAJ and meta-analysisof studies HGAD, EOO3 and HGAI). Maintenance of clinical improvement based on Kaplan-Meier estimated survival curves showed that statistically sig- nificantly greater proportions of patients would maintain response for I year with olanzapine than placebo (p = 0.007), olanzapine 1 mg (p = 0.011) or haloperidol [study HGAJ (p = 0.048) and meta-analysis (p = 0.030)]. These results indicate that treatment with clinically effective doses of olanzapine offered robust and superior effectiveness over placebo and haloperidol in maintaining clinical improvement during long-term continuation therapy. References [I] Be asley Jr CM, Tollef son GO, Tran P. Satterlee W, Sanger T, Hamilton S, The Olanzapine HGAD Study Group (1996): Olanzapine versus placebo and haloperidol: a cute phase results of the North American double-blind olanzapine t rial. Neuropsy chophannacol 14(2): 105-1 t8 (2) Tran PV. Beasley Tollefson GO, Crawford AM, Paul S: Olanzapine: An update on recent clini cal studies. New Clinical Drug Evaluation Unit, 35th Annual Meeting. Orlando, fl orida . June I, 1995