Schizophrenia ziprasidone

Ziprasidone is approved for the treatment of schizophrenia and acute mania. For patients with schizophrenia, ziprasidone is usually started at a dosage of 20-40 mg twice a day. In medically healthy, nonelderly patients, the dose can be rapidly titrated over 2-A days to a typical therapeutic dosage of 60-80 mg twice a day. For patients with acute mania, treatment should be initiated at 40 mg twice... 

Three extensive reviews of ziprasidone have devoted particular attention to the possibility of QT interval prolongation (5-7). Ziprasidone up to 160 mg/day prolongs the QT interval on average 5.9-9.7 ms (data from 4571 patients) a QT interval of over 500 ms was seen in two of 2988 ziprasidone recipients and in one of 440 placebo recipients. In an open study in 31 patients with schizophrenia, ziprasidone given for 21-29 days prolonged the QTc interval by 20 ms (95% Cl = 14, 26). 

Stroup, T. S., Lieberman, J. A., McEvoy, J. P. et al. (2006). Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am. J. Psychiatry, 163, 611-22. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

Taylor D. Ziprasidone in the management of schizophrenia the QT interval issue in context. CNS Drugs 2003 17 423-30. 

Schizophrenia - When deciding among the alternative treatments available for schizophrenia, consider ziprasidone s greater capacity to prolong the QT/QTc interval compared with other antipsychotic drugs. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

A wide range of disorders can benefit from antipsychotic therapy. For example, since the introduction of antipsychotics, 25% fewer hospital beds are occupied by patients with schizophrenia. In particular, the newer antipsychotics hold the promise of benefitting patients once refractory to conventional treatment. Thus, negative, cognitive, and mood symptoms may improve with use of newer agents such as clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. 

TABLE 5-16. Ziprasidone versus placebo or haloperidol for schizophrenia acute treatment... 

Clozapine, risperidone, olanzapine, quetiapine, and ziprasidone have all been approved for the treatment of schizophrenia. Data from long-term open evaluations of clozapine demonstrate that improvement is maintained over time, even when the dose is reduced. Further, patients did not develop tolerance to its antipsychotic effect. Naturalistic reports indicate that an adequate trial for acute response in some patients may be at least 6 months. Further, a small number (8 of 14) of previously refractory patients were successfully maintained on clozapine for up to 2 years ( 215). 

Bagnall A, Lewis RA, Leitner ML, et al. Ziprasidone for schizophrenia and severe mental illness. Cochrane Database Syst Rev 2000 (2) CD001945. 

Harrigan E, Morrissey M, and the Ziprasidone Working Group. The efficacy and safety of 28-day treatment with ziprasidone in schizophrenia/schizoaffective disorder. Presented at the XXth Collegium Internationale Neuropsychopharmacologicum, Melbourne, Australia, June 1996. 

Daniel DG, Zimbroff DL, Potkin SG, et al. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology 1999 20 491-505. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Some patients improve with ziprasidone when conventional antipsychotics fail, although probably not as much as with clozapine. Studies demonstrate that ziprasidone is highly effective for the positive symptoms and also improves the negative symptoms of schizophrenia. Some studies suggest that ziprasidone may improve cognitive functioning in schizophrenia and also in dementia. 

Zotepine, like ziprasidone, is a potent 5-HT2 antagonist which also reduces the reuptake of noradrenaline. Its side effects, sedation and postural hypotension, are attributable to its antagonistic action on histaminel and alpha-1 receptors. Zotepine, which has not yet been marketed in Europe, may have a similar profile to ziprasidone and could be useful in the treatment of depression associated with schizophrenia. Because of the evident clinical superiority of the atypical antipsychotics over the traditional neuroleptics, the World Psychiatric Association Task Force has... 

Power A, O Connor R. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J. Clin. Psychiatry, 2002, 63,... 

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