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Safety and effectiveness of olanzapine versus other antipsychotic drugs in the treatment of out-patients with schizophrenia
S290
P2 Psychotic disorders and antipsychotics
these packages were based on differing symptom severity and response to treatment. Sensitivity analyses assessed the robustness of the model based on different assumptions about service delivery and outcomes. Results: Over 5 years, olanzapine is estimated to be less expensive than haloperidol and risperidone in direct healthcare costs. The predicted outcomes associated with olanzapine treatment were better than those seen with haloperidol for both non-relapse rates and BPRS scores. Outcomes for olanzapine and risperidone were similar although there were numerical advantages for olanzapine. Conclusions: In light of the relatively small cost differences predicted over 5 years, the three drugs appear to offer approximately cost-neutral alternatives. However, the greater effectiveness of olanzapine and risperidone compared with haloperidol suggest that these atypical medications may represent cost-effective treatment options. The differences between olanzapine and risperidone, although in favour of olanzapine, are too small to estimate relative cost-effectiveness of these drugs. As further data become available, a clearer picture of this relative ranking may be possible.
IP.2.1091 Safety and effectiveness of olanzapine versus other antipsychotlc drugs in the treatment of out-patients wlth schizophrenia J.C. Gomez', J.A. Sacristan' , P.R. Carrasco2, C.A. Saiz3, E.F. Carbonel14. ‘Department of Clinical Research, Eli Lilly and Company, Madrid: 2Psychiatrist, Seuilla; ‘Psychiatrist, Hospital Son Dureta, Palma de Mallorca; ‘Psychiatrist, Barcelona, Spain
Introduction: Results of controlled clinical trials need to be confirmed through effectiveness studies in non selected patient cohorts treated according to routine clinical practice. Method: This is a prospective, comparative, observational, naturalistic study, that has included 2967 outpatients with schizophrenia. Patients entered the study when they received a new prescription of an antipsychotic drug, and were followed up for 6 months after treatment initiation. Treatment assignment was based on clinical criteria and the study did not include any experimental intervention. Safety was evaluated through the collection of spontaneous adverse events, and a specific questionnaire for extrapyramidal symptoms (EPS). Global clinical status was measured through the Clinical Global Impression of Severity (CGI-S) and the Global Assessment of Functioning (GAF) Scales. Treatment response was defined prior to the analysis as “at least 2 point decrease in the CGI-S plus a maximum endpoint score of 4 points in the CGI-S”. Results: From the 2967 patients included, 2949 were evaluable and have been included in the analysis. A total of 2128 patients were treated with olanzapine, as monotherapy or combined with other drugs (Olanzapine group), and 821 were treated with other antipsychotic drugs (Control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, severity of symptoms (CGI and GAF), and presence of EPS. Discontinuations due to adverse events have been low (2% in both groups) and without statistically significant differences between treatment groups. Incidence of treatment emergent extrapyramidal symptoms has been significantly lower in the olanzapine group compared to the control group @ < 0.001). Clinical improvement at endpoint, measured through the mean change in the CGI-S and the GAF has been significantly higher in the olanzapine group compared to the control group (p < 0.001). At endpoint, 37.3% of patients in the olanzapine group were treatment-responders compared to 29.9% in the control group (p < 0.001). Conclusion: Despite the limitations and biases which are inherent to observational studies, these results show that olanzapine is safe and effective in non-selected schizophrenic outpatients, and are consistent with the efficacy and safety profile that olanzapine had shown in previous controlled clinical trials.
Ip.2.1101 The effect of olaruapine on the psychopathologic clusters in patients refractory for clozapine treatment E Martenyi’,M. Dossenbach’, S. Metcalfe’,H. Behnakeg, H. Mu&?. 21smeli multicenter study group; ‘Eli Lilly Regional Medical Centec Vienna, Austria
and Methods: In an open label trial 45 treatment refractory schizophrenic patients non responder or intolerant to clozapine treatment were administered olanzapine. Treatment refractory was defined according to the Kane criteria (1.) Severity of psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). Patients were decided as non responders to clozapine treatment, if reduction of BPRSts total scores (extracted from PANSS) was ~20% during the tirst 4 week of clozapine administration. Responder for olanzapine treatment was any patient who achieved 220% symptom reduction in PANSS total score from baseline to the 18th week of therapy. Results: At week 18 (endpoint) 40% of patients achieved more than 20% symptom reduction (olanzapine responders), 24.4% of patients more than 30%, 4.4% more than 40% which did not change oven till 50% improvement. A repeated measures analysis of variance was performed for the total score and each of the four symptom cluster scores separately, on a model including 8 dependent variables (baseline and the seven visit scores; weeks 1, 2,4, 6, 10, 14, 18), constituting a within-subjects factor (time: visit) and one between-subject factor (group: responder/non-responder). The olanzapine-responder and non-responder groups were significantly different in the improvement of PANSS total scores and all psychopathology clusters (group effect p < 0.01, for PANSS total score and all clusters except MS where p = O.O29)(p= 0.0001, all time * group interactions). The improvement from baseline to the subsequent olanzapine treatment week scores showed significant differences between the olanzapine responders and non-responders from the 6th week in the PANSS total scores and in the PS and GP scores (p < 0.05). Thereafter the differences were always significant for all scores (p < 0.05). PANSS total score and all of four symptom clusters showed parallel decreases during the first 4 weeks in the responder and non-responder groups. However the responder group showed a continuous gradual improvement until week 18, in contrast with the worsening of these measures in the non-responder group. Olanzapine treatment was efficacious in 40% of Discussion: treatment-refractory schizophrenics who were non responders to clozapine treatment. Distinction between responders and non-responders to olanzapine was possible after the 6th week of olanzapine administration. This observation is consistent with other studies: several investigators found clinical improvement among antipsychotic non-responders by week 336 (2, 3, 4). Data from the four symptom cluster scores suggested that treatment response could be differentiated not only in terms of overall symptom severity, but also in positive, negative, general psychopathology and affective symptom clusters. Patients
Ip.2.1111 The comparative anti-muscarinic-llke side effect proflles of olanzapine and risperidone treatment in patients with schizophrenia spectrum psychosis F5?Tran, B.R. Basson, J.S. Kennedy, C.M. Beasley Jr., El? Bymaster, G.D. Tollefson. Lilly Research Laboratories. Eli Lilly and Company, Lilly Corpomte Center. Indianapolis, IN 46285, USA Objective: To test the hypothesis that ali?nity differences between olanzapine (OLZ) and risperidone (RISP) would be reflected in objective peripheral antimuscarinic-like (A-M-L) side effects. Change in the PANSS Thought subfactor (PTS) score was also evaluated to determine if antipsychotic doses effective in reducing thought disturbance had been employed.
P2 Psychotic disorders and antipsychotics
these packages were based on differing symptom severity and response to treatment. Sensitivity analyses assessed the robustness of the model based on different assumptions about service delivery and outcomes. Results: Over 5 years, olanzapine is estimated to be less expensive than haloperidol and risperidone in direct healthcare costs. The predicted outcomes associated with olanzapine treatment were better than those seen with haloperidol for both non-relapse rates and BPRS scores. Outcomes for olanzapine and risperidone were similar although there were numerical advantages for olanzapine. Conclusions: In light of the relatively small cost differences predicted over 5 years, the three drugs appear to offer approximately cost-neutral alternatives. However, the greater effectiveness of olanzapine and risperidone compared with haloperidol suggest that these atypical medications may represent cost-effective treatment options. The differences between olanzapine and risperidone, although in favour of olanzapine, are too small to estimate relative cost-effectiveness of these drugs. As further data become available, a clearer picture of this relative ranking may be possible.
IP.2.1091 Safety and effectiveness of olanzapine versus other antipsychotlc drugs in the treatment of out-patients wlth schizophrenia J.C. Gomez', J.A. Sacristan' , P.R. Carrasco2, C.A. Saiz3, E.F. Carbonel14. ‘Department of Clinical Research, Eli Lilly and Company, Madrid: 2Psychiatrist, Seuilla; ‘Psychiatrist, Hospital Son Dureta, Palma de Mallorca; ‘Psychiatrist, Barcelona, Spain
Introduction: Results of controlled clinical trials need to be confirmed through effectiveness studies in non selected patient cohorts treated according to routine clinical practice. Method: This is a prospective, comparative, observational, naturalistic study, that has included 2967 outpatients with schizophrenia. Patients entered the study when they received a new prescription of an antipsychotic drug, and were followed up for 6 months after treatment initiation. Treatment assignment was based on clinical criteria and the study did not include any experimental intervention. Safety was evaluated through the collection of spontaneous adverse events, and a specific questionnaire for extrapyramidal symptoms (EPS). Global clinical status was measured through the Clinical Global Impression of Severity (CGI-S) and the Global Assessment of Functioning (GAF) Scales. Treatment response was defined prior to the analysis as “at least 2 point decrease in the CGI-S plus a maximum endpoint score of 4 points in the CGI-S”. Results: From the 2967 patients included, 2949 were evaluable and have been included in the analysis. A total of 2128 patients were treated with olanzapine, as monotherapy or combined with other drugs (Olanzapine group), and 821 were treated with other antipsychotic drugs (Control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, severity of symptoms (CGI and GAF), and presence of EPS. Discontinuations due to adverse events have been low (2% in both groups) and without statistically significant differences between treatment groups. Incidence of treatment emergent extrapyramidal symptoms has been significantly lower in the olanzapine group compared to the control group @ < 0.001). Clinical improvement at endpoint, measured through the mean change in the CGI-S and the GAF has been significantly higher in the olanzapine group compared to the control group (p < 0.001). At endpoint, 37.3% of patients in the olanzapine group were treatment-responders compared to 29.9% in the control group (p < 0.001). Conclusion: Despite the limitations and biases which are inherent to observational studies, these results show that olanzapine is safe and effective in non-selected schizophrenic outpatients, and are consistent with the efficacy and safety profile that olanzapine had shown in previous controlled clinical trials.
Ip.2.1101 The effect of olaruapine on the psychopathologic clusters in patients refractory for clozapine treatment E Martenyi’,M. Dossenbach’, S. Metcalfe’,H. Behnakeg, H. Mu&?. 21smeli multicenter study group; ‘Eli Lilly Regional Medical Centec Vienna, Austria
and Methods: In an open label trial 45 treatment refractory schizophrenic patients non responder or intolerant to clozapine treatment were administered olanzapine. Treatment refractory was defined according to the Kane criteria (1.) Severity of psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). Patients were decided as non responders to clozapine treatment, if reduction of BPRSts total scores (extracted from PANSS) was ~20% during the tirst 4 week of clozapine administration. Responder for olanzapine treatment was any patient who achieved 220% symptom reduction in PANSS total score from baseline to the 18th week of therapy. Results: At week 18 (endpoint) 40% of patients achieved more than 20% symptom reduction (olanzapine responders), 24.4% of patients more than 30%, 4.4% more than 40% which did not change oven till 50% improvement. A repeated measures analysis of variance was performed for the total score and each of the four symptom cluster scores separately, on a model including 8 dependent variables (baseline and the seven visit scores; weeks 1, 2,4, 6, 10, 14, 18), constituting a within-subjects factor (time: visit) and one between-subject factor (group: responder/non-responder). The olanzapine-responder and non-responder groups were significantly different in the improvement of PANSS total scores and all psychopathology clusters (group effect p < 0.01, for PANSS total score and all clusters except MS where p = O.O29)(p= 0.0001, all time * group interactions). The improvement from baseline to the subsequent olanzapine treatment week scores showed significant differences between the olanzapine responders and non-responders from the 6th week in the PANSS total scores and in the PS and GP scores (p < 0.05). Thereafter the differences were always significant for all scores (p < 0.05). PANSS total score and all of four symptom clusters showed parallel decreases during the first 4 weeks in the responder and non-responder groups. However the responder group showed a continuous gradual improvement until week 18, in contrast with the worsening of these measures in the non-responder group. Olanzapine treatment was efficacious in 40% of Discussion: treatment-refractory schizophrenics who were non responders to clozapine treatment. Distinction between responders and non-responders to olanzapine was possible after the 6th week of olanzapine administration. This observation is consistent with other studies: several investigators found clinical improvement among antipsychotic non-responders by week 336 (2, 3, 4). Data from the four symptom cluster scores suggested that treatment response could be differentiated not only in terms of overall symptom severity, but also in positive, negative, general psychopathology and affective symptom clusters. Patients
Ip.2.1111 The comparative anti-muscarinic-llke side effect proflles of olanzapine and risperidone treatment in patients with schizophrenia spectrum psychosis F5?Tran, B.R. Basson, J.S. Kennedy, C.M. Beasley Jr., El? Bymaster, G.D. Tollefson. Lilly Research Laboratories. Eli Lilly and Company, Lilly Corpomte Center. Indianapolis, IN 46285, USA Objective: To test the hypothesis that ali?nity differences between olanzapine (OLZ) and risperidone (RISP) would be reflected in objective peripheral antimuscarinic-like (A-M-L) side effects. Change in the PANSS Thought subfactor (PTS) score was also evaluated to determine if antipsychotic doses effective in reducing thought disturbance had been employed.