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Ziprasidone versus risperidone in schizophrenia: An eight-week, double-blind trial with forty four-week continuation
18. Therapeutics: Treatment Trials
273
NP1 scores were paralleled by statistically significant changes in BPRS scores (normalized to baseline) at 6 (27+/-l 2%) and 12 (29+/t 3%) weeks. Additionally, combined hallucinations, suspiciousness, irritability, and agitation subscale scores of the BPRS were reduced by 36+/-11% (P=0.03, t-test) at 6 weeks and 46+/-13% (P<0.02, ttest) at 12 weeks. MMSE scores showed an average improvement (not significant, P>0.05) of 2 points. There were no significant changes (P>0.05) in FAQ and GDS scores, no increase in SAS or AIMS scores, and no clinically significant changes in laboratory values and vital signs over the 12-week treatment period. There was a strong trend toward improvement in sleep, and the 5 patients who had a measurable sleep disturbance at baseline showed a statistically significant treatment effect (P<0.05). These findings suggest that quetiapine may be an effective and well-tolerated therapeutic agent for the treatment of elderly patients with LBD-associated psychosis.
NEUROCOGNITIVE THERAPY
ENHANCEMENT
IN S C H I Z O P H R E N I A :
DURABILITY
OF EFFECTS ON NEUROPSYCHOLOGICAL TEST PERFORMANCE
SIX MONTHS
AFTER
TRAINING M. D. Bell,* G. Bryson, T. Greig, B. Wexler Psychiatry, Yale University School of Medicine, New Haven, CT, USA Several recent reports and reviews of neurocognitive retraining suggest that such methods may have favorable effects on cognitive functioning in schizophrenia. However, in the 12 controlled trials of cognitive training that have appeared in the literature, retesting occurred immediately after training. Therefore, it remains unknown whether benefits of training persist beyond its conclusion. In the present study, subjects were reassessed six-months after completion of a program of neurocognitive enhancement therapy (NET)to determine the durability of training effects when compared to an active control group. A previous study revealed that NET training led to improvement on neuropsychological test performance using tasks that were different than those that comprised the training. These results suggested that NET training had led to some generalized cognitive benefits, particularly in memory and executive function. Ninety-nine subjects with schizophrenia or schizoaffective disorder were randomly assigned to NET plus work therapy (WT) or work therapy alone. NET included software training on attention, memory and executive tasks, a social information group, and feedback on work behavior. The active intervention ended after six months. Neuropsychological testing was done at intake, 5 months, and 12 months (6 months after the conclusion of treatment). Repeated measures analysis of variance revealed that subjects receiving NET plus WT showed significantly greater improvements on executive function (p < .05) and working memory (p < .01). As many as 60% of NET+WT group improved on some measures. Comparison of effect sizes over time showed durability of training effects, Analyses of individual measures over time by condition indicated significant linear trends for Digits Backwards, Trails B, Wisconsin Card Sorting Task Categories Complete, and WCST Percent Conceptual Level. This is the first study to test the question of durability of effects six months after cognitive training. This sustained improvement in cognitive performance may be due in part to the length and intensity of NET+WT in which subjects averaged more than 2 training session per week for six months. These results offer further support for the potential benefits of cognitive training in schizophrenia.
ZIPRASIDONE
VERSUS RISPERIDONE
SCHIZOPHRENIA:
AN EIGHT-WEEK,
IN DOUBLE-
BLIND TRIAL WITH FORTY FOUR-WEEK CONTINUATION I. Benattia,* D. Addington, C. Pantelis, M. Dineen, S. Murray Pfizer,, Inc., New York, NY,, USA We compared the efficacy and tolerability of ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder. In an 8-week, multicenter, double-blind trial, patients were randomized to ziprasidone 40-80 mg BID or risperidone 3-5 mg BID. Primary efficacy evaluations were Positive and Negative Syndrome Scale (PANSS) Total and Clinical Global Impression-Severity (CGI-S) scores; secondary variables included PANSS Negative Subscale score, Brief Psychiatric Rating Scale (BPRSd) Total and Core items scores, and Global Assessment of Functioning (GAF). Primary analysis was based on evaluable patients (_>14days of treatment). Patients who completed the 8-week trial were eligible to enter a 44-week, double-blind continuation study. Based on a predetermined criterion (lower limit of 95% CI for ratio of mean change with ziprasidone to mean change with risperidone >0.60), equivalent improvements were observed in both groups for PANSS Total score (mean change ratio 0.95, lower limit 0.78) and CGI-S (mean change ratio 0.87, lower limit 0.70). Similarly, equivalent improvements were seen in PANSS Negative score, BPRSD Total and Core scores, and GAE In tolerability assessments, ziprasidone (n=149) ,andrisperidone (n=147) were comparable; however, risperidone had a significantly higher mean Movement Disorder Burden Score (MDBS) and higher incidences of prolactin elevation and clinically significant (_>7%) weight gain. In the 44-week continuation study, patients in both the ziprasidone (n=59) and risperidone (n=76) groups exhibited comparable, sustained improvement in primary and secondary efficacy variables from baseline of the 8-week study. Mean MDBS and incidences of prolactin elevation and clinicalIy significant weight gain remained greater in the risperidone group than in the ziprasidone group. Thus, in this 8-week, double-blind, randomized trial, ziprasidone demonstrated antipsychotic efficacy comparable to risperidone, with lower movement disorder burden and lower incidences of prolactin elevation and clinically significant weight gain. Similar results were obtained in the 44-week continuation study, providing further support for ziprasidone's longterm efficacy and tolerability.
SAFETY AND EFFICACY OF OLANZAPINE
IN
TREATING PATIENTS WITH SCHIZOPHRENIA I. Bitter,* V. Maciulis, R. Milasiunas, A. Dembinskas, L. E. Radavicius, A. L. Kaunas, D. J. Walker, M. Dossenbach Area Medical Center Vienna, Eli Lilly Ges.m.b.H, Vienna, Wien, Austria Objective: To determine if patients with schizophrenia could be switched to olanzapine and show improvement in both symptomatotogy and in drug-induced side effects. Methods: Twenty-four patients in Lithuania entered this 13-week, multicenter, open-label study. Patients started on 10 mg/day of olanzapine which could be adjusted upward or downward by 5 mg/day between the dosing range of 5 to 20 mg/day. The primary efficacy measure was the BPRS
International Congress on Schizophrenia Research 2003
273
NP1 scores were paralleled by statistically significant changes in BPRS scores (normalized to baseline) at 6 (27+/-l 2%) and 12 (29+/t 3%) weeks. Additionally, combined hallucinations, suspiciousness, irritability, and agitation subscale scores of the BPRS were reduced by 36+/-11% (P=0.03, t-test) at 6 weeks and 46+/-13% (P<0.02, ttest) at 12 weeks. MMSE scores showed an average improvement (not significant, P>0.05) of 2 points. There were no significant changes (P>0.05) in FAQ and GDS scores, no increase in SAS or AIMS scores, and no clinically significant changes in laboratory values and vital signs over the 12-week treatment period. There was a strong trend toward improvement in sleep, and the 5 patients who had a measurable sleep disturbance at baseline showed a statistically significant treatment effect (P<0.05). These findings suggest that quetiapine may be an effective and well-tolerated therapeutic agent for the treatment of elderly patients with LBD-associated psychosis.
NEUROCOGNITIVE THERAPY
ENHANCEMENT
IN S C H I Z O P H R E N I A :
DURABILITY
OF EFFECTS ON NEUROPSYCHOLOGICAL TEST PERFORMANCE
SIX MONTHS
AFTER
TRAINING M. D. Bell,* G. Bryson, T. Greig, B. Wexler Psychiatry, Yale University School of Medicine, New Haven, CT, USA Several recent reports and reviews of neurocognitive retraining suggest that such methods may have favorable effects on cognitive functioning in schizophrenia. However, in the 12 controlled trials of cognitive training that have appeared in the literature, retesting occurred immediately after training. Therefore, it remains unknown whether benefits of training persist beyond its conclusion. In the present study, subjects were reassessed six-months after completion of a program of neurocognitive enhancement therapy (NET)to determine the durability of training effects when compared to an active control group. A previous study revealed that NET training led to improvement on neuropsychological test performance using tasks that were different than those that comprised the training. These results suggested that NET training had led to some generalized cognitive benefits, particularly in memory and executive function. Ninety-nine subjects with schizophrenia or schizoaffective disorder were randomly assigned to NET plus work therapy (WT) or work therapy alone. NET included software training on attention, memory and executive tasks, a social information group, and feedback on work behavior. The active intervention ended after six months. Neuropsychological testing was done at intake, 5 months, and 12 months (6 months after the conclusion of treatment). Repeated measures analysis of variance revealed that subjects receiving NET plus WT showed significantly greater improvements on executive function (p < .05) and working memory (p < .01). As many as 60% of NET+WT group improved on some measures. Comparison of effect sizes over time showed durability of training effects, Analyses of individual measures over time by condition indicated significant linear trends for Digits Backwards, Trails B, Wisconsin Card Sorting Task Categories Complete, and WCST Percent Conceptual Level. This is the first study to test the question of durability of effects six months after cognitive training. This sustained improvement in cognitive performance may be due in part to the length and intensity of NET+WT in which subjects averaged more than 2 training session per week for six months. These results offer further support for the potential benefits of cognitive training in schizophrenia.
ZIPRASIDONE
VERSUS RISPERIDONE
SCHIZOPHRENIA:
AN EIGHT-WEEK,
IN DOUBLE-
BLIND TRIAL WITH FORTY FOUR-WEEK CONTINUATION I. Benattia,* D. Addington, C. Pantelis, M. Dineen, S. Murray Pfizer,, Inc., New York, NY,, USA We compared the efficacy and tolerability of ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder. In an 8-week, multicenter, double-blind trial, patients were randomized to ziprasidone 40-80 mg BID or risperidone 3-5 mg BID. Primary efficacy evaluations were Positive and Negative Syndrome Scale (PANSS) Total and Clinical Global Impression-Severity (CGI-S) scores; secondary variables included PANSS Negative Subscale score, Brief Psychiatric Rating Scale (BPRSd) Total and Core items scores, and Global Assessment of Functioning (GAF). Primary analysis was based on evaluable patients (_>14days of treatment). Patients who completed the 8-week trial were eligible to enter a 44-week, double-blind continuation study. Based on a predetermined criterion (lower limit of 95% CI for ratio of mean change with ziprasidone to mean change with risperidone >0.60), equivalent improvements were observed in both groups for PANSS Total score (mean change ratio 0.95, lower limit 0.78) and CGI-S (mean change ratio 0.87, lower limit 0.70). Similarly, equivalent improvements were seen in PANSS Negative score, BPRSD Total and Core scores, and GAE In tolerability assessments, ziprasidone (n=149) ,andrisperidone (n=147) were comparable; however, risperidone had a significantly higher mean Movement Disorder Burden Score (MDBS) and higher incidences of prolactin elevation and clinically significant (_>7%) weight gain. In the 44-week continuation study, patients in both the ziprasidone (n=59) and risperidone (n=76) groups exhibited comparable, sustained improvement in primary and secondary efficacy variables from baseline of the 8-week study. Mean MDBS and incidences of prolactin elevation and clinicalIy significant weight gain remained greater in the risperidone group than in the ziprasidone group. Thus, in this 8-week, double-blind, randomized trial, ziprasidone demonstrated antipsychotic efficacy comparable to risperidone, with lower movement disorder burden and lower incidences of prolactin elevation and clinically significant weight gain. Similar results were obtained in the 44-week continuation study, providing further support for ziprasidone's longterm efficacy and tolerability.
SAFETY AND EFFICACY OF OLANZAPINE
IN
TREATING PATIENTS WITH SCHIZOPHRENIA I. Bitter,* V. Maciulis, R. Milasiunas, A. Dembinskas, L. E. Radavicius, A. L. Kaunas, D. J. Walker, M. Dossenbach Area Medical Center Vienna, Eli Lilly Ges.m.b.H, Vienna, Wien, Austria Objective: To determine if patients with schizophrenia could be switched to olanzapine and show improvement in both symptomatotogy and in drug-induced side effects. Methods: Twenty-four patients in Lithuania entered this 13-week, multicenter, open-label study. Patients started on 10 mg/day of olanzapine which could be adjusted upward or downward by 5 mg/day between the dosing range of 5 to 20 mg/day. The primary efficacy measure was the BPRS
International Congress on Schizophrenia Research 2003