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Change in positive symptoms with olanzapine compared to other antipsychotic agents
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of patients to interact and integrate into the community. This report presents data from two double-blind clinical trials on the negative symptom profile of olanzapine compared to atypical antipsychotic agents, risperidone (6 months; N = 339) and clozapine (18 weeks; N = 180). Effects on negative symptoms were assessed using the mean change from baseline to endpoint on the Scale for the Assessment of Negative Symptoms (SANS), and the negative subscores of the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS). On both the SANS and the BPRS negative subscore, olanzapine consistently demonstrated statistical superiority over risperidone in treating negative symptoms after 6 months (SANS, p=0.02 and BPRSNEo, p=0.29), while numerically superior on the PANSS negative subscore. In comparison to clozapine, olanzapine did not demonstrate a statistically significant difference in reduction of negative symptoms as measured by PANSS and BPRS negative subscores. However, as measured by both scales, olanzapine consistently had a numerical advantage over clozapine. The lack of statistical significance of the observed clinical effect can be explained by reduced power due to a sample size powered to detect differences in overall symptomatology. In conclusion, compared to alternative atypical antipsychotic therapies, olanzapine was statistically superior to risperidone and as effective as clozapine in the treatment of negative symptoms.
compared to haloperidol (p~<0.01) and fluphenazine ( p = 0.004). Against atypical comparators, olanzapine was statistically superior to clozapine (p = 0.006), and numerically superior to risperidone on the SAS. In 3 of 5 conventional comparator studies, there was a significantly lower incidence in severity of dyskinetic events with olanzapine compared to haloperidol (p ~<0.011 ), as measured by the AIMS. Olanzapine was numerically superior to fluphenazine in decreasing AIMS scores. Against atypical comparators, olanzapine produced numerically greater improvements than clozapine. In conclusion, olanzapine generally produced greater improvement in EPS than alternative antipsychotics, resulting in a more satisfactory safety profile and better treatment outcome.
EFFICACY OF ARIPIPRAZOLE IN PSYCHOTIC DISORDERS: COMPARISON WITH H A L O P E R I D O L A N D PLACEBO J. Kane, G. Ingenito*, M. Ali* Hillside Hospital, Glen Oaks', NY, USA and Otsuka America Pharmaceutical Inc. *, Rockville, MD, USA
C H A N G E IN POSITIVE SYMPTOMS WITH OLANZAPINE COMPARED TO OTHER ANTIPSYCHOTIC AGENTS S.R. David, C.C. Taylor, K.M. Meehan Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, USA Extrapyramidal symptoms (EPS) - - akathisia, parkinsonism, and tardive dyskinesia - - are serious and common side effects of neuroleptic treatment. This report presents global data from 8 clinical trials (N= 3270) on the EPS profile of olanzapine (8 studies; 2.5 to 25mg/day; n=2131) compared to both conventional (haloperidol [5 studies; 5 to 20mg/day; n=852] and fluphenazine [ 1 study; 6 to 21 mg/day; n = 30]) and atypical (risperidone [1 study; 4 to 12mg/day; n = 167] and clozapine [1 study; 200 to 600mg/day; n=90]) antipsychotics. Improvement was assessed using mean change from baseline to endpoint on the Barnes or Hillside Akathisia Scale, the Simpson-Angus Scale (SAS), and the Abnormal Involuntary Movement Scale (AIMS). In 4 of 5 conventional comparator studies, akithisia scores were significantly decreased with olanzapine compared to haloperidol (Barnes, p~<0.007) and fluphenazine (Hillside, p = 0.017 ). Against atypical comparators, olanzapine produced numerically greater akathisia improvements than risperidone at 8 weeks, but not 6 months. In 4 of 5 conventional comparator studies, SAS scores were significantly decreased with olanzapine
Aripiprazole, a novel agent with a unique spectrum of pharmacologic activities, is in development for the treatment of the symptoms associated with psychotic disorders. The first Phase III clinical trial was a double-blind, four-week comparison of two fixed doses of aripiprazole ( 15 and 30 mg), haloperidol (10 mg) and placebo in over 400 hospitalized patients with a DSM-IV diagnosis of acute relapse of schizophrenia or schizoaffective disorder. Efficacy of both doses of aripiprazole and haloperidol were significantly superior to placebo (change in PANSS-total, BPRS-total, LOCF; p<0.01). However, responder analysis (30% decrease from baseline in PANSStotal at last visit) indicated both doses of aripiprazole to be significantly better than placebo (p <0.05), while the response rate for haloperidol was not significantly different from placebo (p < 0.1 ). Aripiprazole was well tolerated; the number of subjects discontinuing due to adverse events was less than placebo and haloperidol. No clinically meaningful increase in QTc prolongation was observed in aripiprazole treated subjects. Extrapyramidal symptomatology with aripiprazole was not different from placebo. Additionally, fewer patients treated with aripiprazole received at least one administration of benztropine (10.8-16.8%) than those treated with haloperidol (36.0%), The incidence of clinically significant increases in prolactin levels with aripiprazole was comparable to placebo and substantially less than haloperidol. The incidence of clinically significant increases in body weight with aripiprazole was less than with haloperidol. This study clearly demonstrates the clinical efficacy and tolerability of aripiprazole and suggests it may be an important future therapeutic option.
of patients to interact and integrate into the community. This report presents data from two double-blind clinical trials on the negative symptom profile of olanzapine compared to atypical antipsychotic agents, risperidone (6 months; N = 339) and clozapine (18 weeks; N = 180). Effects on negative symptoms were assessed using the mean change from baseline to endpoint on the Scale for the Assessment of Negative Symptoms (SANS), and the negative subscores of the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS). On both the SANS and the BPRS negative subscore, olanzapine consistently demonstrated statistical superiority over risperidone in treating negative symptoms after 6 months (SANS, p=0.02 and BPRSNEo, p=0.29), while numerically superior on the PANSS negative subscore. In comparison to clozapine, olanzapine did not demonstrate a statistically significant difference in reduction of negative symptoms as measured by PANSS and BPRS negative subscores. However, as measured by both scales, olanzapine consistently had a numerical advantage over clozapine. The lack of statistical significance of the observed clinical effect can be explained by reduced power due to a sample size powered to detect differences in overall symptomatology. In conclusion, compared to alternative atypical antipsychotic therapies, olanzapine was statistically superior to risperidone and as effective as clozapine in the treatment of negative symptoms.
compared to haloperidol (p~<0.01) and fluphenazine ( p = 0.004). Against atypical comparators, olanzapine was statistically superior to clozapine (p = 0.006), and numerically superior to risperidone on the SAS. In 3 of 5 conventional comparator studies, there was a significantly lower incidence in severity of dyskinetic events with olanzapine compared to haloperidol (p ~<0.011 ), as measured by the AIMS. Olanzapine was numerically superior to fluphenazine in decreasing AIMS scores. Against atypical comparators, olanzapine produced numerically greater improvements than clozapine. In conclusion, olanzapine generally produced greater improvement in EPS than alternative antipsychotics, resulting in a more satisfactory safety profile and better treatment outcome.
EFFICACY OF ARIPIPRAZOLE IN PSYCHOTIC DISORDERS: COMPARISON WITH H A L O P E R I D O L A N D PLACEBO J. Kane, G. Ingenito*, M. Ali* Hillside Hospital, Glen Oaks', NY, USA and Otsuka America Pharmaceutical Inc. *, Rockville, MD, USA
C H A N G E IN POSITIVE SYMPTOMS WITH OLANZAPINE COMPARED TO OTHER ANTIPSYCHOTIC AGENTS S.R. David, C.C. Taylor, K.M. Meehan Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, USA Extrapyramidal symptoms (EPS) - - akathisia, parkinsonism, and tardive dyskinesia - - are serious and common side effects of neuroleptic treatment. This report presents global data from 8 clinical trials (N= 3270) on the EPS profile of olanzapine (8 studies; 2.5 to 25mg/day; n=2131) compared to both conventional (haloperidol [5 studies; 5 to 20mg/day; n=852] and fluphenazine [ 1 study; 6 to 21 mg/day; n = 30]) and atypical (risperidone [1 study; 4 to 12mg/day; n = 167] and clozapine [1 study; 200 to 600mg/day; n=90]) antipsychotics. Improvement was assessed using mean change from baseline to endpoint on the Barnes or Hillside Akathisia Scale, the Simpson-Angus Scale (SAS), and the Abnormal Involuntary Movement Scale (AIMS). In 4 of 5 conventional comparator studies, akithisia scores were significantly decreased with olanzapine compared to haloperidol (Barnes, p~<0.007) and fluphenazine (Hillside, p = 0.017 ). Against atypical comparators, olanzapine produced numerically greater akathisia improvements than risperidone at 8 weeks, but not 6 months. In 4 of 5 conventional comparator studies, SAS scores were significantly decreased with olanzapine
Aripiprazole, a novel agent with a unique spectrum of pharmacologic activities, is in development for the treatment of the symptoms associated with psychotic disorders. The first Phase III clinical trial was a double-blind, four-week comparison of two fixed doses of aripiprazole ( 15 and 30 mg), haloperidol (10 mg) and placebo in over 400 hospitalized patients with a DSM-IV diagnosis of acute relapse of schizophrenia or schizoaffective disorder. Efficacy of both doses of aripiprazole and haloperidol were significantly superior to placebo (change in PANSS-total, BPRS-total, LOCF; p<0.01). However, responder analysis (30% decrease from baseline in PANSStotal at last visit) indicated both doses of aripiprazole to be significantly better than placebo (p <0.05), while the response rate for haloperidol was not significantly different from placebo (p < 0.1 ). Aripiprazole was well tolerated; the number of subjects discontinuing due to adverse events was less than placebo and haloperidol. No clinically meaningful increase in QTc prolongation was observed in aripiprazole treated subjects. Extrapyramidal symptomatology with aripiprazole was not different from placebo. Additionally, fewer patients treated with aripiprazole received at least one administration of benztropine (10.8-16.8%) than those treated with haloperidol (36.0%), The incidence of clinically significant increases in prolactin levels with aripiprazole was comparable to placebo and substantially less than haloperidol. The incidence of clinically significant increases in body weight with aripiprazole was less than with haloperidol. This study clearly demonstrates the clinical efficacy and tolerability of aripiprazole and suggests it may be an important future therapeutic option.