Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: An 8-week, double-blind, multicenter trial

Department of Psychiatry, Foothills Medical Center, Calgary, Alberta, Canada.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2004; 65(12):1624-33.
Source: PubMed


More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder.
Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997.
Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).
Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone.

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    • "In a controlled study comparing olanzapine versus risperidone, a somehow shorter time were needed to reach the remission in olanzapine group.[28] In a controlled study comparing ziprasidone with risperidone, both agents equally improved psychotic symptom.[29] Another clinical trial compared haloperidol with olanzapine showed that two drugs didn’t have statistically different level of improvement after 24 h of treatment.[30] "
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    ABSTRACT: Objective: Antipsychotic medications are the frontline treatment for the most psychotic disorders. The aim of this study is to compare the onset of action of the first and second generation antipsychotics and the rate of their side-effects in the treatment of acute psychosis. Methods: In a double-blind, controlled clinical trial, 40 acute psychotic patients were randomly allocated in four groups and treated with each of the four antipsychotics: olanzapine, risperidone, haloperidol or thiothixene. The onset of action of each drug was assessed by the Positive and Negative Symptoms Scale. The data were analyzed by Wilcoxon (Gehan) survival and Log Rank analysis, using SPSS version 20.0. Findings: Initial response was observed in 97.5% (N = 39) of subjects during 2 weeks of intervention. The mean time to the first response was 6.15 ± 2.9 days and this was significantly shorter for risperidone than others. The most common side-effects were sedation and drug induced Parkinsonism. Conclusion: Risperidone represented shorter onset of action for the treatment of acute psychotic symptoms compared with olanzapine, haloperidol and thiothixene.
    Journal of Pharmacy Practice and Research 10/2013; 2(4):138-44. DOI:10.4103/2279-042X.128142
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    • "However, because week 1 ziprasidone dose of standard-dose start group and low-dose start group were significantly different, there is possibility that the rate of dose titration, not only initial dose, can affect the results which favored standard-dose start. Addington et al. also reported that slower titration contributed to a higher dropout rate for ziprasidone during the first two weeks in schizophrenic patients.21 "
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    ABSTRACT: We investigated the efficacy and tolerability of ziprasidone combined with divalproex to determine the relationship between the initial dose of ziprasidone and the treatment effect among Korean patients with acute bipolar manic or mixed disorders. This study was a 6-week, open-label, prospective investigation of Korean patients with an acute manic or mixed episode of bipolar disorder. Sixty-five patients were recruited. The patients were categorized based on the initial dose of ziprasidone as follows: low (20-79 mg/day) and standard (80 mg/day). Ziprasidone was given in combination with divalproex in flexible doses, according to the clinical response and tolerability. The response and remission rates were significantly higher in the standard-dose group than the low-dose group. The combination of ziprasidone and divalproex was well-tolerated and adverse events were mostly mild with no statistically significant increase in body weight. The results of this study showed that a standard starting dose of ziprasidone in combination with divalproex for bipolar disorder is more effective than a low starting dose.
    Psychiatry investigation 09/2011; 8(3):207-13. DOI:10.4306/pi.2011.8.3.207 · 1.28 Impact Factor
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    • "As the author pointed out, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).20 "
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    ABSTRACT: Since schizophrenia is considered one of the top ten causes of disease-related disability in the world, the development of second-generation (atypical) antipsychotics (SGAs) has increased the hopes of psychiatrists. SGAs, however, cannot be considered a unique pharmacological class since each SGA has many complex pharmacologic actions, only some of which are shared with other SGAs. Even though manyantipsychotics have similar efficacy on average, prescribers may be able to achieve better than average results by considering differences in selecting a specific drug for a specific patient. Clinicians know that each patient is unique. In order to achieve best outcomes for the individual patient, the better therapy is the therapy tailored for the single patient. With this article, we provide information on a relatively new antipsychotic ziprasidone released in 2001 by Pfizer for the treatment of schizophrenia. Compared with other first line atypical antipsychotics ziprasidone has a unique profile due to potent interaction with serotonergic receptors and lesser action upon α1 adrenergic, H1 and M1 antagonist activities. This paper describes the development of ziprasidone, its unique properties and its metabolically-friendly profile including its receptor binding affinities, pharmacokinetics, CNS activity results of clinical efficacy and relevant clinical trials. Safety, efficacy and patient preference are also examined. The available literature on ziprasidone of the last five years is reviewed.
    02/2011; 3:1-16. DOI:10.4137/JCNSD.S4138
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Christos Pantelis