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A 28-WEEK, RANDOMIZED, DOUBLE-BLIND STUDY OF OLANZAPINE VERSUS ARIPIPRAZOLE IN THE TREATMENT OF SCHIZOPHRENIA
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279 acute-agitation cluster and total scores from the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity o f Illness scale (CGI-S). Extrapyramidal side effect was assessed by Abnormal Involuntary Movement Scale (AIMS) and Simpson-Angus Scale (SAS). Any adverse effects occurred after medication was recorded. Sedation was assessed by means of a 4-point scale. All scales were performed before taking medication and after 30 minutes and 1, 2, 6, and 24 hours after receiving the initial dose of study medication. The data was analyzed on an intent-to-treat (ITT) basis with the last-observation-carried-forward (LOCF) for the endpoint. The PANSS, YMRS and CGI-S scores were analyzed by repeated measures of analysis of variance (ANOVA) in terms of the withinsubject factors and the between-subject factors over the study periods. An interaction effect was also considered between time and the treatment group. SAS, BARS, and AIMS scores were analyzed using the same ANOVA model in PANSS. Descriptive statistics and chi-square test were performed for the group difference in the frequencies of side effects. Odds ratio (OD) and 95% confidence interval (CI) were presented where appropriate. P < 0.05 (two-tailed) was considered statistically significant. Statistical analyses were performed using the SPSS 10.0 for Windows program. Results: There were no differences in sex, age, diagnoses, severity of symptoms before taking medication between two groups. The 5-item acute-agitation cluster from PANSS and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by the group interaction effect (F=71.85, p<0.0001). Tolerability and safety by SAS and AIMS were not different between two groups. There were no serious adverse events in both groups. Conclusions: For the emergency treatment of psychotic agitation, risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol. Therefore, it is considerable to choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation. References [1] Currier GW, Chou JC, Feifel D, Bossie CA, Turkoz I, Mahmoud RA, et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. The Jour nal of clinical psychiatry 2004; 65: 386-94. [2] Currier GW, Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. The Journal of clinical psychiatry 2 001; 62: 153-7. [3] Currier GW, Trenton A. Pharmacological treatment of psychotic agitation. CNS drugs 2002; 16: 219-28.
623 – A 28-WEEK, RANDOMIZED, DOUBLE-BLIND STUDY OF OLANZAPINE VERSUS ARIPIPRAZOLE IN THE TREATMENT OF SCHIZOPHRENIA John M. Kane 1 , Olawale Osuntokun 2 , Ludmila Kryzhanovskaya 2 , Wen Xu 2 , Virginia Stauffer 2 , Susan Watson 2 , Olawale Osuntokun 3 1 Zucker Hillside Hospital, Glen Oaks, NY; 2 Eli Lilly and Company, Indianapolis, IN; 3 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA [email protected], [email protected] Introduction: The current study evaluated the effectiveness of olanzapine (OLZ) versus aripiprazole (APZ) in patients with schizophrenia. Methods: Patients 18 to 65 with schizophrenia were randomized to either OLZ (n=281) or APZ (n=285) for 28 weeks of double-blind treatment. The primary outcome was time to all-cause discontinuation. Symptom efficacy was measured by Positive and Negative Syndrome Scale (PANSS) total change from baseline (LOCF). Time-to-event data were analyzed via the Kaplan Meier method and log-rank test. Results: Treatment groups did not differ significantly in time to allcause discontinuation (p=.067) or discontinuation rates (OLZ 42.7%, APZ 50.2%, p=.053). OLZ patients had a significantly greater LS
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mean decrease in the PANSS (30.2) than APZ patients (25. 9, p=.014). Mean weight change (kg) was +3.4 for OLZ and +0.3 for APZ (p<.001). Fasting mean glucose change (mg/dL) was +4.9 for OLZ and +0.9 for APZ (p=.045). Percent of patients with baseline glucose <100 and glucose <126 at any time was 1.7% for OLZ and 0.6% for APZ (p=.623). Fasting mean total cholesterol change (mg/dL) was +4.1 for OLZ and 9.8 for APZ (p<.001). Percent of patients with baseline total cholesterol <200 and cholesterol <240 at any time was 9.2% for OLZ and 1.5% for APZ (p=.008). Conclusions: OLZ and APZ groups did not differ significantly on the primary outcome. OLZ patients had significantly greater improvement in symptom efficacy. Significantly greater increases in weight, glucose, and total cholesterol were observed in OLZ treated patients. Results are generally consistent with previous clinical trials comparing the 2 therapies. References [1] McQuade RD, Stock E, Marcus R, Jody D, Gharbia NA, Vanveggel S, Archibald D, Carson WH: A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study. J Clin Psychiatry 2004; 65(Suppl 18):47- 56
624 – EFFICACY AND TOLERABILITY OF SWITCHING FROM OLANZAPINE, RISPERIDONE, AND HALOPERIDOL TO ZIPRASIDONE IN PATIENTS WITH SCHIZOPHRENIA: AN INTERNATIONAL MULTICENTER STUDY Onur Karayal 1 , Koksal Alptekin 2 , Wing Lowe 1 , Jamal Hafez 3 , Shlomo Brook 4 , Cengiz Akkaya 5 , Errikos Tzebelikos 6 1 Pfizer Inc., New York, New York, USA; 2 Dokuz Eylul University Medical Faculty, Balcova, Izmir; 3 Dar Al Ajaza Al Islamyah Hospital, Beirut;Lebanon; 4 Witwatersrand University, Johannesburg; 5 Uludag University Medical School, Gorukle, Bursa; 6 Sismanoglion General Hospital, Athens Onur.Karayal@pfizer.com Introduction: Some patients with schizophrenia switch medications due to lack of efficacy or poor tolerability; improvement in symptoms and side effects following a switch must be assessed. Methods: In a 12-week, open-label, baseline-controlled, flexible dose switch study, adult outpatients with schizophrenia experiencing suboptimal efficacy or tolerability issues were switched from haloperidol (n = 99), olanzapine (n = 82), or risperidone (n = 104) to ziprasidone (80–160 mg/d; dosed twice daily with food). The primary efficacy evaluation was BPRS score at week 12. Safety evaluations included change from baseline in movement disorders (SAS, BAS, AIMS), body weight, prolactin, and fasting lipids levels. Statistical tests were 1-sided, noninferiority comparisons with correction for multiple comparisons (0.025/3 significance level), for primary efficacy end point, or 2-sided (0.05 significance level), for secondary end points. Results: BPRS scores improved significantly following switch to ziprasidone. Week 12 mean change from baseline (SD) for patients switched from haloperidol, olanzapine, or risperidone was –11.3 (16.3), –6.3 (14.2), and –9.9 (13.2), respectively (p < 0.0001 vs baseline). Movement disorders, measured by SAS, BAS, and AIMS, improved significantly for subjects switched from haloperidol or risperidone. Change in weight (kg ± SD) from baseline was 0.4 ± 3.97, –2.0±3.99 (p < 0.001), and –0.6±3.21, respectively. Conclusions: Patients switched to ziprasidone demonstrated improvement in symptoms and movement disorders, with a neutral weight effect. Ziprasidone is an appropriate switch option for patients experiencing suboptimal efficacy or poor tolerability with their current treatment. Acknowledgements: This study was funded by Pfizer, Inc. References [1] McEvoy JP, Lieberman JA, Stroup TS, et al, for the CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not
623 – A 28-WEEK, RANDOMIZED, DOUBLE-BLIND STUDY OF OLANZAPINE VERSUS ARIPIPRAZOLE IN THE TREATMENT OF SCHIZOPHRENIA John M. Kane 1 , Olawale Osuntokun 2 , Ludmila Kryzhanovskaya 2 , Wen Xu 2 , Virginia Stauffer 2 , Susan Watson 2 , Olawale Osuntokun 3 1 Zucker Hillside Hospital, Glen Oaks, NY; 2 Eli Lilly and Company, Indianapolis, IN; 3 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA [email protected], [email protected] Introduction: The current study evaluated the effectiveness of olanzapine (OLZ) versus aripiprazole (APZ) in patients with schizophrenia. Methods: Patients 18 to 65 with schizophrenia were randomized to either OLZ (n=281) or APZ (n=285) for 28 weeks of double-blind treatment. The primary outcome was time to all-cause discontinuation. Symptom efficacy was measured by Positive and Negative Syndrome Scale (PANSS) total change from baseline (LOCF). Time-to-event data were analyzed via the Kaplan Meier method and log-rank test. Results: Treatment groups did not differ significantly in time to allcause discontinuation (p=.067) or discontinuation rates (OLZ 42.7%, APZ 50.2%, p=.053). OLZ patients had a significantly greater LS
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mean decrease in the PANSS (30.2) than APZ patients (25. 9, p=.014). Mean weight change (kg) was +3.4 for OLZ and +0.3 for APZ (p<.001). Fasting mean glucose change (mg/dL) was +4.9 for OLZ and +0.9 for APZ (p=.045). Percent of patients with baseline glucose <100 and glucose <126 at any time was 1.7% for OLZ and 0.6% for APZ (p=.623). Fasting mean total cholesterol change (mg/dL) was +4.1 for OLZ and 9.8 for APZ (p<.001). Percent of patients with baseline total cholesterol <200 and cholesterol <240 at any time was 9.2% for OLZ and 1.5% for APZ (p=.008). Conclusions: OLZ and APZ groups did not differ significantly on the primary outcome. OLZ patients had significantly greater improvement in symptom efficacy. Significantly greater increases in weight, glucose, and total cholesterol were observed in OLZ treated patients. Results are generally consistent with previous clinical trials comparing the 2 therapies. References [1] McQuade RD, Stock E, Marcus R, Jody D, Gharbia NA, Vanveggel S, Archibald D, Carson WH: A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study. J Clin Psychiatry 2004; 65(Suppl 18):47- 56
624 – EFFICACY AND TOLERABILITY OF SWITCHING FROM OLANZAPINE, RISPERIDONE, AND HALOPERIDOL TO ZIPRASIDONE IN PATIENTS WITH SCHIZOPHRENIA: AN INTERNATIONAL MULTICENTER STUDY Onur Karayal 1 , Koksal Alptekin 2 , Wing Lowe 1 , Jamal Hafez 3 , Shlomo Brook 4 , Cengiz Akkaya 5 , Errikos Tzebelikos 6 1 Pfizer Inc., New York, New York, USA; 2 Dokuz Eylul University Medical Faculty, Balcova, Izmir; 3 Dar Al Ajaza Al Islamyah Hospital, Beirut;Lebanon; 4 Witwatersrand University, Johannesburg; 5 Uludag University Medical School, Gorukle, Bursa; 6 Sismanoglion General Hospital, Athens Onur.Karayal@pfizer.com Introduction: Some patients with schizophrenia switch medications due to lack of efficacy or poor tolerability; improvement in symptoms and side effects following a switch must be assessed. Methods: In a 12-week, open-label, baseline-controlled, flexible dose switch study, adult outpatients with schizophrenia experiencing suboptimal efficacy or tolerability issues were switched from haloperidol (n = 99), olanzapine (n = 82), or risperidone (n = 104) to ziprasidone (80–160 mg/d; dosed twice daily with food). The primary efficacy evaluation was BPRS score at week 12. Safety evaluations included change from baseline in movement disorders (SAS, BAS, AIMS), body weight, prolactin, and fasting lipids levels. Statistical tests were 1-sided, noninferiority comparisons with correction for multiple comparisons (0.025/3 significance level), for primary efficacy end point, or 2-sided (0.05 significance level), for secondary end points. Results: BPRS scores improved significantly following switch to ziprasidone. Week 12 mean change from baseline (SD) for patients switched from haloperidol, olanzapine, or risperidone was –11.3 (16.3), –6.3 (14.2), and –9.9 (13.2), respectively (p < 0.0001 vs baseline). Movement disorders, measured by SAS, BAS, and AIMS, improved significantly for subjects switched from haloperidol or risperidone. Change in weight (kg ± SD) from baseline was 0.4 ± 3.97, –2.0±3.99 (p < 0.001), and –0.6±3.21, respectively. Conclusions: Patients switched to ziprasidone demonstrated improvement in symptoms and movement disorders, with a neutral weight effect. Ziprasidone is an appropriate switch option for patients experiencing suboptimal efficacy or poor tolerability with their current treatment. Acknowledgements: This study was funded by Pfizer, Inc. References [1] McEvoy JP, Lieberman JA, Stroup TS, et al, for the CATIE Investigators. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not