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Effect of cloricromene during ischemia and reperfusion of rabbit hindlimb: evidence for an involvement of leukocytes in reperfusion-mediated tissue and vascular injury.

2017-05-18

The study was a 12-week, open label, multicenter, non comparative trial on oral ziprasidone. 106 patients with DSM-IV schizophrenia were switched to ziprasidone from their previous antipsychotic without a washout phase. The study required fixed dosing with ziprasidone. For the first week the patient received 80 mg of study drug daily, followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120 mg, or 160 mg total daily dose could be given at the discretion of the investigator. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD), Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Changes in overall body weight were also evaluated.

Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.

Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.

Even with the limitations of any non-comparative study, these results suggest that the IM/oral sequential administration of ziprasidone is an effective and well tolerated therapeutic option in the management of acute exacerbations of schizophrenia in agitated patients.

QTc interval prolongation may appear as a consequence of both typical and atypical antipsychotic treatments. Ziprasidone, which is effective in treating schizophrenia, is associated with QTc prolongation. Although the prolongation of QTc with ziprasidone treatment is often pronounced, there is a scarce number of cases reported about the relationship between ziprasidone and QTc prolongation. Of the three cases presented in this case series, two cases showed values exceeding 0.50 s with ziprasidone treatment.

To determine the doses of haloperidol as a comparator drug in randomized controlled trials (RCTs) with atypical antipsychotics in patients with schizophrenia and to compare these doses with the officially recommended doses for haloperidol in the United States and the United Kingdom.

Double-blind controlled trials with adequate samples (n > 100) were identified through search of PubMed/MEDLINE and computerized abstracts from 2004-2006 meetings of the American Psychiatric Association, International Conference on Bipolar Disorder, and Collegium Internationale Neuro-Psychopharmacolium using key words mania, adjunct, and combination.

The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations.

This study investigated the effect of ziprasidone augmentation therapy on sleep architecture in bipolar depression.

The abstracts, titles, and index terms of studies were searched using the following key words: aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine in conjunction with mania, manic, and bipolar.

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.