- Email: [email protected]
Olanzapine versus risperidone and haloperidol in treatment of schizophrenia
150
conventional neuroleptics as well as Clozapine and other atypicals, who responded to between 40-60 mg of Olanzapine per day as measured on GAS and CGI scores as well as clinical assessment. The side effects were minimal except for two cases who had some early EPS and all patients were monitored with ECG, LFT and FBC along with pulse, blood pressure and temperature. This suggests that the effective dose of Olanzapine may be much higher than suggested and one must postulate that in clinical trials low doses are used to keep down the EPS scores. Further work is indicated using high dose Olanzapine for treatment resistant schizophrenia.
EFFICACY
O F A 12 W E E K
OLANZAPINE REFRACTORY
TRIAL
OF
IN TREATMENT SCHIZOPHRENIA
SCHIZOAFFECTIVE
OR
DISORDER
S. R a t a k o n d a , C.E. Miller, J.M. G o r m a n , Z.A. S h a r i f
CohmThia Universio'/Creedmoor Psychiatric Center. 80 45 Winchester Bird, Queens Village, N Y 11427. USA Objective. To examine the efficacy of olanzapine in treating schizophrenia or schizoaffective disorder refractory to standard antipsychotics. Methods: Patients with schizophrenia or schizoaffective disorder, refractory to an adequate trial of at least one neuroleptic, were given olanzapine for 12 weeks with at least 6 of these weeks being at a dose of >20 mg/day. Assessments were conducted at two week intervals using PANSS, Calgary Depression Scale and Extrapyramidal Symptom Rating Scale. Results. Six patients with schizophrenia and two with schizoaffective disorder have so far completed the protocol. Clozapine had previously been effective in two patients but was discontinued for side effects. No patient had failed a clozapine trial. At study entry, the mean total PANSS score was 104, duration of illness 17 years, and length of hospitalization 29 months. Mean maximum daily olanzapine dose was 26 mg. For the group, mean improvement at twelve weeks was 11% in total PANSS score, 13% in positive subscale and 15% in negative subscale. Using >25'¼> improvement in total PANSS score as criterion, none of the patients could be categorized as responders. Only one subject had significant depressive symptoms, which showed a 36% improvement. Side effects were infrequent and included parkinsonism, akathesia and sedation. Body weight increased by a mean of 2% over baseline, with three subjects showing > 5% increase. Conclusion: Unlike clozapine, olanzapine is not effective in treating patients refractory to standard antipsychotics. This inference is limited by the small sample size.
OLANZAPINE COMPARED TO FLUPHENAZINE IN THE TREATMENT ACUTE SCHIZOPHRENIA
OF
N. M i m i c a a, M. D o s s e n b a c h 2, P. Friedel 2, V. F o l n e g o v i c - S m a l c ~, G. M a k a r i c ~, M. Jakovljevic 3, B. Uglesic 4
t UniversiO, Department +~[Psyehiatry, PsTchiatrie Hospital Vrapce, Bolnieka Cesta 32, HR-IO090 Zagreb, Croatia; 2Eli Lilly GmbH, Area Medical Center Vienna, Bariehgasse 40 42, A-1030 Vienna, Austria; 3University Clinic +)['Zagreb, Kispatieeva 12, HR-41000, Zagreb, Croatia; 4psychiatric Clinic Split, Spinguceva ul., HR-58000 Split, Croatia Background." Olanzapine, a new antipsychotic agent with an atypical profile, has so far been compared to haloperidol and risperidone. It was the aim of this study to compare the safety and efficacy of olanzapine with fluphenazine. Methods: This study was conducted in three centres in Croatia. After a screening period of 2 9 days patients were randomised to olanzapine or fluphenazine. Evaluations were made weekly in the first 6 weeks, then monthly for the remaining 16 weeks. The PANSS, BPRS, and CGI rating scales were used as efficacy instruments. Safety measures included adverse events, vital signs, laboratory tests (clinical chemistry), SAS, HAS and AIMS rating scales. Results: Sixty patients entered the study, 55 (27 olanzapine, 28 fluphenazine) were evaluable for efficacy analysis. The mean age was 34.8 years and 46.7% were male. The olanzapine treatment group showed significantly greater improvement in the BPRS total score (olanzapine - 2 5 . 8 versus fluphenazine 16.5), PANSS total score (olanzapine - 4 5 . 7 versus fluphenazine - 2 9 . 5 ) , and CGI severity score (olanzapine - 2 . 2 versus fluphenazine - t . 3 ) . A statistically significant greater proportion of olanzapine-treated patients achieved a response of at least 40% improvement in the BPRSo 6 total score than fluphenazine treated group (olanzapine 80.8% vs. Fluphenazine 57.7%). Olanzapine-treated patients reported significantly fewer treatment-emergent adverse events than the fluphenazine group. SAS, HAS and AIMS showed that the olanzapine group improved statistically significant compared to the fluphenazine group. Conclusion: The study represented here suggests that olanzapine is superior in the efficacy as well as in the safety profile compared to fluphenazine.
OLANZAPINE VERSUS RISPERIDONE HALOPERIDOL IN TREATMENT OF SCHIZOPHRENIA
AND
B. Jones. G. Tollefson
Canadian Cognition and Outcome in Sekilophrenia Study Group Eli Lilly and Company. Lilly Corporate Center, Indianapolis, Indiana 46285. USA It is hypothesized that in stable patients early in illness, an improvement in clinical symptoms of schizophrenia can be
151
accompanied by an improvement in cognitive dysfunction and can also positively impact a patient's quality of life and resource utilization. In this multicentre, randomized, double-blind, parallel study, 65 stable patients in the first five years of illness were randomized to one of three treatment groups: olanzapine in the dose range of 5 mg to 20 mg per day, risperidone in the dose range of 4mg to 10mg per day, or haloperidol in the dose range of 5 mg to 20 mg per day. Patients were excluded from the trial if they exhibited baseline PANSS>90. After a one-month stabilization period and a one-week washout/screening period, patients were randomized and followed on therapy for 54 weeks. Dosing after the first week of therapy was carried out on a per patient basis and at the judgement of the attending physician. Results comparing olanzapine to risperidone and olanzapine to haloperidol for efficacy (neuropsychological exams, PANSS), safety (ESR5;, Barnes Akathisia), quality of life (QLS, SF-36), and resource utilization are presented. Tests of the primary measures are performed both for endpoint values and change-from-baseline at endpoint. In this select population, olanzapine shows marked benefits on cognition, especially, compared with risperidone and haloperidol.
OLANZAPINE VERSUS HALOPERIDOL THE TREATMENT OF FIRST EPISODE PSYCHOSIS
IN
T.M. Sanger, J.A. Lieberman, M. Tohen, G.D. Tollefson
Lilly Research Laboratories, Lilly Corporate ('enter. Indianapolis, IN 46285, USA These analyses explore the effect of olanzapine versus haloperidol in the treatment of first episode psychosis in an international, multicenter, double-blind, parallel trial. This trial compared the efficacy and safety of a single dose range of olanzapine, 5 -20 mg/day, to a single dose range of haloperidol, 5 21)mg/day, in the treatment of 1996 in- and out-patients with a DSM-III-R diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder. Patients were assigned by random allocation to double-blind therapy in the ratio of 2 olanzapine to 1 haloperidol assignment. The acute phase of the trial was 6 weeks in length which was followed by a double-blind responder extension and a open-label nonresponder extension. Of the 1996 patients enrolled in the trial, 83 (59 olanzapine, 24 haloperidol) were in their first episode of psychosis with an episode duration of _<5 years and age at onset of _<45 years. In this subgroup of first episode patients, olanzapine was statistically significantly superior to haloperidol in the reduction of BPRS total score, BPRS negative score, PANSS total score, and PANSS positive score from baseline to endpoint of the acute phase (last-observation-carriedforward ). Also, haloperidol first episode patients suffered statistically significantly more EPS and akathisia than olanzapine first episode patients as measured by changes in SimpsonAngus total and Barnes global item from baseline to endpoint of the acute therapy.
OLANZAPINE IN THE TREATMENT SCHIZOAFFECTIVE DISORDER
OF
P. Tran, Y. Lu, T. Sanger, C. Beasley, G. Tollefson
Eli Lilly and Company, Lilly Corporate Center. Indianapolis, Indiana 46285. USA Study HGAJ was an international, multicenter, double-blind trial which compared the efficacy and safety of a single doserange of olanzapine ( 5--20 rag) to a single dose-range of haloperidol (5-20rag) in the treatment of 1996 patients with a DSM I II-R diagnosis of schizophrenia, schizophreniform disorder and schizoaffective disorder. During the acute phase (6 weeks), a total of 300 patients with schizoaffective disorder were enrolled ( 177 schizoaffective, bipolar type and 123 schizoaffective, depressive type). The efficacy data on this subset of patients with scbizoaffective disorder will be presented in this poster. Overall, the olanzapine-treated patients with schizoaffective disorder and the subgroup of patients with schizoaffective disorder, bipolar type experienced statistically significantly greater improvement on mean change from baseline to endpoint in BPRS total, PANSS total, PANSS negative, CGI severity and MADRS total scores when compared with the haloperidol treatment group. For the subgroup of patients with the diagnosis of schizoaffective, depressed type, the mean improvement in the olanzapine-treated patients was only marginally statistically significantly greater than that in the haloperidol-treated patients, however the magnitude of the differences in BPRS total, PANSS total, and PANSS negative scores was greater than that observed in the subgroup of patients with schizoaffective, bipolar type. We conclude that olanzapine is significantly superior to haloperidol in the treatment of patients suffering from schizoaffective disorder.
OLANZAPINE IN THE TREATMENT ELDERLY PATIENTS WITH SCHIZOPHRENIA AND RELATED PSYCHOTIC DISORDERS
OF
S.G. Reams, T.M. Sanger, C.M. Beasley Jr.
Eli Lilly and Company, Indianapolis, Lilly Corporate Center Indiana 46285. USA Elderly psychotic patients are particularly sensitive to the adverse effects associated with conventional antipsychotic therapies. Atypical antipsychotics, such as olanzapine, may offer significant therapeutic advantages. In a 6-week double-blind trial in patients meeting diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder, 59 patients, aged 65 years or older, were randomized to treatment with olanzapine (5 20 rag/day) or haloperidol (5 20 mg/day). Olanzapine-treated patients had greater improvement in BPRS total, PANSS total and negative, and MADRS total scores, although the difference did not reach statistical significance. Treatment-emergent adverse events commonly reported (_> 10% incidence) by olanzapine-treated patients included insomnia, somnolence, and accidental injury. The incidence rates were
conventional neuroleptics as well as Clozapine and other atypicals, who responded to between 40-60 mg of Olanzapine per day as measured on GAS and CGI scores as well as clinical assessment. The side effects were minimal except for two cases who had some early EPS and all patients were monitored with ECG, LFT and FBC along with pulse, blood pressure and temperature. This suggests that the effective dose of Olanzapine may be much higher than suggested and one must postulate that in clinical trials low doses are used to keep down the EPS scores. Further work is indicated using high dose Olanzapine for treatment resistant schizophrenia.
EFFICACY
O F A 12 W E E K
OLANZAPINE REFRACTORY
TRIAL
OF
IN TREATMENT SCHIZOPHRENIA
SCHIZOAFFECTIVE
OR
DISORDER
S. R a t a k o n d a , C.E. Miller, J.M. G o r m a n , Z.A. S h a r i f
CohmThia Universio'/Creedmoor Psychiatric Center. 80 45 Winchester Bird, Queens Village, N Y 11427. USA Objective. To examine the efficacy of olanzapine in treating schizophrenia or schizoaffective disorder refractory to standard antipsychotics. Methods: Patients with schizophrenia or schizoaffective disorder, refractory to an adequate trial of at least one neuroleptic, were given olanzapine for 12 weeks with at least 6 of these weeks being at a dose of >20 mg/day. Assessments were conducted at two week intervals using PANSS, Calgary Depression Scale and Extrapyramidal Symptom Rating Scale. Results. Six patients with schizophrenia and two with schizoaffective disorder have so far completed the protocol. Clozapine had previously been effective in two patients but was discontinued for side effects. No patient had failed a clozapine trial. At study entry, the mean total PANSS score was 104, duration of illness 17 years, and length of hospitalization 29 months. Mean maximum daily olanzapine dose was 26 mg. For the group, mean improvement at twelve weeks was 11% in total PANSS score, 13% in positive subscale and 15% in negative subscale. Using >25'¼> improvement in total PANSS score as criterion, none of the patients could be categorized as responders. Only one subject had significant depressive symptoms, which showed a 36% improvement. Side effects were infrequent and included parkinsonism, akathesia and sedation. Body weight increased by a mean of 2% over baseline, with three subjects showing > 5% increase. Conclusion: Unlike clozapine, olanzapine is not effective in treating patients refractory to standard antipsychotics. This inference is limited by the small sample size.
OLANZAPINE COMPARED TO FLUPHENAZINE IN THE TREATMENT ACUTE SCHIZOPHRENIA
OF
N. M i m i c a a, M. D o s s e n b a c h 2, P. Friedel 2, V. F o l n e g o v i c - S m a l c ~, G. M a k a r i c ~, M. Jakovljevic 3, B. Uglesic 4
t UniversiO, Department +~[Psyehiatry, PsTchiatrie Hospital Vrapce, Bolnieka Cesta 32, HR-IO090 Zagreb, Croatia; 2Eli Lilly GmbH, Area Medical Center Vienna, Bariehgasse 40 42, A-1030 Vienna, Austria; 3University Clinic +)['Zagreb, Kispatieeva 12, HR-41000, Zagreb, Croatia; 4psychiatric Clinic Split, Spinguceva ul., HR-58000 Split, Croatia Background." Olanzapine, a new antipsychotic agent with an atypical profile, has so far been compared to haloperidol and risperidone. It was the aim of this study to compare the safety and efficacy of olanzapine with fluphenazine. Methods: This study was conducted in three centres in Croatia. After a screening period of 2 9 days patients were randomised to olanzapine or fluphenazine. Evaluations were made weekly in the first 6 weeks, then monthly for the remaining 16 weeks. The PANSS, BPRS, and CGI rating scales were used as efficacy instruments. Safety measures included adverse events, vital signs, laboratory tests (clinical chemistry), SAS, HAS and AIMS rating scales. Results: Sixty patients entered the study, 55 (27 olanzapine, 28 fluphenazine) were evaluable for efficacy analysis. The mean age was 34.8 years and 46.7% were male. The olanzapine treatment group showed significantly greater improvement in the BPRS total score (olanzapine - 2 5 . 8 versus fluphenazine 16.5), PANSS total score (olanzapine - 4 5 . 7 versus fluphenazine - 2 9 . 5 ) , and CGI severity score (olanzapine - 2 . 2 versus fluphenazine - t . 3 ) . A statistically significant greater proportion of olanzapine-treated patients achieved a response of at least 40% improvement in the BPRSo 6 total score than fluphenazine treated group (olanzapine 80.8% vs. Fluphenazine 57.7%). Olanzapine-treated patients reported significantly fewer treatment-emergent adverse events than the fluphenazine group. SAS, HAS and AIMS showed that the olanzapine group improved statistically significant compared to the fluphenazine group. Conclusion: The study represented here suggests that olanzapine is superior in the efficacy as well as in the safety profile compared to fluphenazine.
OLANZAPINE VERSUS RISPERIDONE HALOPERIDOL IN TREATMENT OF SCHIZOPHRENIA
AND
B. Jones. G. Tollefson
Canadian Cognition and Outcome in Sekilophrenia Study Group Eli Lilly and Company. Lilly Corporate Center, Indianapolis, Indiana 46285. USA It is hypothesized that in stable patients early in illness, an improvement in clinical symptoms of schizophrenia can be
151
accompanied by an improvement in cognitive dysfunction and can also positively impact a patient's quality of life and resource utilization. In this multicentre, randomized, double-blind, parallel study, 65 stable patients in the first five years of illness were randomized to one of three treatment groups: olanzapine in the dose range of 5 mg to 20 mg per day, risperidone in the dose range of 4mg to 10mg per day, or haloperidol in the dose range of 5 mg to 20 mg per day. Patients were excluded from the trial if they exhibited baseline PANSS>90. After a one-month stabilization period and a one-week washout/screening period, patients were randomized and followed on therapy for 54 weeks. Dosing after the first week of therapy was carried out on a per patient basis and at the judgement of the attending physician. Results comparing olanzapine to risperidone and olanzapine to haloperidol for efficacy (neuropsychological exams, PANSS), safety (ESR5;, Barnes Akathisia), quality of life (QLS, SF-36), and resource utilization are presented. Tests of the primary measures are performed both for endpoint values and change-from-baseline at endpoint. In this select population, olanzapine shows marked benefits on cognition, especially, compared with risperidone and haloperidol.
OLANZAPINE VERSUS HALOPERIDOL THE TREATMENT OF FIRST EPISODE PSYCHOSIS
IN
T.M. Sanger, J.A. Lieberman, M. Tohen, G.D. Tollefson
Lilly Research Laboratories, Lilly Corporate ('enter. Indianapolis, IN 46285, USA These analyses explore the effect of olanzapine versus haloperidol in the treatment of first episode psychosis in an international, multicenter, double-blind, parallel trial. This trial compared the efficacy and safety of a single dose range of olanzapine, 5 -20 mg/day, to a single dose range of haloperidol, 5 21)mg/day, in the treatment of 1996 in- and out-patients with a DSM-III-R diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder. Patients were assigned by random allocation to double-blind therapy in the ratio of 2 olanzapine to 1 haloperidol assignment. The acute phase of the trial was 6 weeks in length which was followed by a double-blind responder extension and a open-label nonresponder extension. Of the 1996 patients enrolled in the trial, 83 (59 olanzapine, 24 haloperidol) were in their first episode of psychosis with an episode duration of _<5 years and age at onset of _<45 years. In this subgroup of first episode patients, olanzapine was statistically significantly superior to haloperidol in the reduction of BPRS total score, BPRS negative score, PANSS total score, and PANSS positive score from baseline to endpoint of the acute phase (last-observation-carriedforward ). Also, haloperidol first episode patients suffered statistically significantly more EPS and akathisia than olanzapine first episode patients as measured by changes in SimpsonAngus total and Barnes global item from baseline to endpoint of the acute therapy.
OLANZAPINE IN THE TREATMENT SCHIZOAFFECTIVE DISORDER
OF
P. Tran, Y. Lu, T. Sanger, C. Beasley, G. Tollefson
Eli Lilly and Company, Lilly Corporate Center. Indianapolis, Indiana 46285. USA Study HGAJ was an international, multicenter, double-blind trial which compared the efficacy and safety of a single doserange of olanzapine ( 5--20 rag) to a single dose-range of haloperidol (5-20rag) in the treatment of 1996 patients with a DSM I II-R diagnosis of schizophrenia, schizophreniform disorder and schizoaffective disorder. During the acute phase (6 weeks), a total of 300 patients with schizoaffective disorder were enrolled ( 177 schizoaffective, bipolar type and 123 schizoaffective, depressive type). The efficacy data on this subset of patients with scbizoaffective disorder will be presented in this poster. Overall, the olanzapine-treated patients with schizoaffective disorder and the subgroup of patients with schizoaffective disorder, bipolar type experienced statistically significantly greater improvement on mean change from baseline to endpoint in BPRS total, PANSS total, PANSS negative, CGI severity and MADRS total scores when compared with the haloperidol treatment group. For the subgroup of patients with the diagnosis of schizoaffective, depressed type, the mean improvement in the olanzapine-treated patients was only marginally statistically significantly greater than that in the haloperidol-treated patients, however the magnitude of the differences in BPRS total, PANSS total, and PANSS negative scores was greater than that observed in the subgroup of patients with schizoaffective, bipolar type. We conclude that olanzapine is significantly superior to haloperidol in the treatment of patients suffering from schizoaffective disorder.
OLANZAPINE IN THE TREATMENT ELDERLY PATIENTS WITH SCHIZOPHRENIA AND RELATED PSYCHOTIC DISORDERS
OF
S.G. Reams, T.M. Sanger, C.M. Beasley Jr.
Eli Lilly and Company, Indianapolis, Lilly Corporate Center Indiana 46285. USA Elderly psychotic patients are particularly sensitive to the adverse effects associated with conventional antipsychotic therapies. Atypical antipsychotics, such as olanzapine, may offer significant therapeutic advantages. In a 6-week double-blind trial in patients meeting diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder, 59 patients, aged 65 years or older, were randomized to treatment with olanzapine (5 20 rag/day) or haloperidol (5 20 mg/day). Olanzapine-treated patients had greater improvement in BPRS total, PANSS total and negative, and MADRS total scores, although the difference did not reach statistical significance. Treatment-emergent adverse events commonly reported (_> 10% incidence) by olanzapine-treated patients included insomnia, somnolence, and accidental injury. The incidence rates were