Olanzapine Versus Ziprasidone: Results of a 28-Week Double-Blind Study in Patients With Schizophrenia

Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Hamburg, Germany
American Journal of Psychiatry (Impact Factor: 12.3). 11/2005; 162(10):1879-87. DOI: 10.1176/appi.ajp.162.10.1879
Source: PubMed


The efficacy and safety of olanzapine were compared with those of ziprasidone.
This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.
The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.
Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.

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Available from: Wagner Gattaz, Jun 18, 2014
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    • "Recent studies have found that newer SGAs such as aripiprazole or ziprasidone have shown lower liability for inducing weight gain and metabolic adverse reactions than olanzapine or risperidone (Breier et al., 2005; Kinon et al., 2006; Komossa et al., 2009). Several studies have reported that switching from treatments with high metabolic risk to ziprasidone (Alptekin et al., 2009; Stroup et al., 2006; Weiden et al., 2008) or to aripiprazole (Stroup et al., 2011) is an effective strategy for improving metabolic outcomes and reducing weight. "
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    ABSTRACT: This randomized open-label study compared the incidence of metabolic side effects of aripiprazole, ziprasidone and quetiapine in a population of medication-naïve first-episode psychosis patients. A total of 202 subjects were enrolled. Body weight, body mass index, leptin, fasting lipids and fasting glycaemic parameters were measured at baseline and at 3months follow-up. A hundred and sixty-six patients completed the follow-up and were included in the analyses. A high proportion of patients experienced a significant weight increase (>7% of their baseline weight): 23% ziprasidone (n=12), 32% with quetiapine (n=16) and 45% with aripiprazole (n=31). Patients treated with aripiprazole gained significantly more weight than the patients in the ziprasidone group (1.2kg [SD=4.1] versus 4.3kg [SD=4.8], respectively). The increase in leptin levels was greater in women treated with aripiprazole than in those treated with ziprasidone (p=0.030). Mean prolactin levels significantly increased in patients treated with quetiapine and ziprasidone but not in those treated with aripiprazole. Patients treated with quetiapine and aripiprazole showed a significant increase in total cholesterol and LDL-cholesterol plasma levels. Quetiapine-treated patients resulted in a higher increase in LDL-cholesterol than patients treated with ziprasidone (p=0.021). No other significant differences between groups were found. No significant changes in glycaemic parameters were observed. Our results suggest that ziprasidone has a lower liability for inducing weight gain and lipid abnormalities than aripiprazole or quetiapine.
    Schizophrenia Research 08/2014; 159(1). DOI:10.1016/j.schres.2014.07.045 · 3.92 Impact Factor
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    • "In a comparison of olanzapine and ziprasidone for the 6-week treatment of patients with acute schizophrenia or schizoaffective disorder, both antipsychotics were efficacious in improving positive, negative and depressive symptoms without significant treatment differences, suggesting that ziprasidone was as efficacious as olanzapine in improving the Calgary Depression Scale for Schizophrenia score [78]. Another study that compared olanzapine and ziprasidone in patients with schizophrenia demonstrated significantly greater improvement in olanzapine-treated patients on positive, negative and depressive symptoms at the 28-week study, suggesting that treatment response may differentiate over longer treatment durations [79]. In a systematic review and meta-analysis, Leucht et al. [80] reported that olanzapine was found to have superior efficacy compared to aripiprazole, quetiapine, risperidone and ziprasidone. "
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    ABSTRACT: Depressive symptoms are common in schizophrenia and they can occur during any phase of the disorder. Early diagnosis, adequate differential diagnosis and promptly initiated interventions have been shown to reduce further deterioration of illness and to improve patients' quality of life. Common psychiatric rating scales for early detection of depressive symptoms in schizophrenia are Calgary Depression Scale for Schizophrenia and Hamilton Depression Rating Scale, but the most appropriate assessment instrument today regarding this topic is Calgary Depression Scale for Schizophrenia. Treatment of depression in schizophrenia consists of a combination of pharmacologic and psychosocial approach. Atypical antipsychotics have advantages over typical in reducing depressive symptoms in the context of schizophrenia. Most of the studies referred that clozapine, olanzapine, quetiapine and risperidone have an antidepressant spectrum of activity in patients with schizophrenia. Antidepressant augmentation of antipsychotic treatment in schizophrenic patients with depressive symptoms improves depressive symptomatology, particularly SSRI and SNRI augmentation.
    EPMA Journal, The 12/2011; 2(4):391-402. DOI:10.1007/s13167-011-0103-0
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    • "The study of first episode patients included an acute phase (first 12 weeks) and the longer-term phase (the following 24 weeks). These 6 studies have been previously published comparing olanzapine with risperidone (HGBG, OLZ: 10 to 20 mg/day; RISP: 4 to 12 mg/day) [25], quetiapine (HGJB, OLZ: 10 to 20 mg/day; QUE: 300 to 700 mg/day) [26], ziprasidone (HGHJ, OLZ: 10 to 20 mg/day; ZIP: 80 to 160 mg/day) [27], Aripiprazole (HGLB, OLZ: 15 to 20 mg/day; ARI: 15 to 30 mg/day) [28] and haloperidol (HGDH: acute treatment phase, the initial dose titration ranges for the first 6 weeks were OLZ [5 to 10 mg/day] and HAL [l2 to 6 mg/day; for the second 6 weeks of the acute phase and for the entire continuation phase, the allowed doses were OLZ [5 to 20 mg/day and haloperidol 2 to 20 mg/day]) [29-31]. Table 1 presents these studies, their sample sizes and the study duration. "
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    ABSTRACT: When treating schizophrenia, improving patients' productivity level is a major goal considering schizophrenia is a leading cause of functional disability. Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia. However, little has been done to systematically investigate productivity levels in schizophrenia. We set out to better understand the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications. We also assessed the links between productivity level and other clinical outcomes. This post hoc analysis used data from 6 randomized, double-blind clinical trials of patients with schizophrenia or schizoaffective disorder, with each trial being of approximately 6 months duration. Change in productivity level was compared between olanzapine-treated patients (HGBG, n = 172; HGHJ, n = 277; HGJB, n = 171; HGLB, n = 281; HGGN, n = 159; HGDH, n = 131) and patients treated with other antipsychotic medications (separately vs. haloperidol [HGGN, n = 97; HGDH, n = 132], risperidone [HGBG, n = 167; HGGN, n = 158], quetiapine [HGJB, n = 175], ziprasidone [HGHJ, n = 271] and aripiprazole [HGLB, n = 285]). Productivity was defined as functional activities/work including working for pay, studying, housekeeping and volunteer work. Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75% to 100% of the time. Chronically ill patients treated with olanzapine (OLZ) experienced significantly greater improvement in productivity when compared to patients treated with risperidone (RISP) (OLZ = 0.22 ± 1.19, RISP = -0.03 ± 1.17, p = 0.033) or ziprasidone (ZIP) (OLZ = 0.50 ± 1.38, ZIP = 0.25 ± 1.27, p = 0.026), but did not significantly differ from the quetiapine, aripiprazole or haloperidol treatment groups. Among first episode patients, OLZ therapy was associated with greater improvements in productivity levels compared to haloperidol (HAL), during the acute phase (OLZ = -0.31 ± 1.59, HAL = -0.69 ± 1.56, p = 0.011) and over the long-term (OLZ = 0.10 ± 1.50, HAL = -0.32 ± 1.91, p = 0.008). Significantly more chronically ill and first episode patients treated with olanzapine showed moderately high (>50%-75% of the time) and high levels of productivity (>75%-100% of the time) at endpoint, when compared to risperidone or haloperidol-treated patients (p < .05), respectively. Higher productivity level was associated with significantly higher study completion rates and better scores on the positive, negative, disorganized thoughts, hostility and depression subscales of the Positive and Negative Symptom Scale (PANSS). Some antipsychotic medications significantly differed in beneficial impact on productivity level in the long-term treatment of patients with schizophrenia. Findings further highlight the link between clinical and functional outcomes, showing significant associations between higher productivity, lower symptom severity and better persistence on therapy. identifier NCT00088049; NCT00036088.
    BMC Psychiatry 05/2011; 11(1):87. DOI:10.1186/1471-244X-11-87 · 2.21 Impact Factor
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