Ziprasidone studies

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. 

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. 

The so-called atypical antipsychotics represent one of the newest options for managing disruptive behavioral syndromes. Because they have yet to be studied in patients who have suffered a TBI, we certainly cannot recommend the atypical antipsychotics for routine first-line use. Nevertheless, an atypical antipsychotic might prove helpful when other medicines aren t providing satisfactory results in the management of severe behavioral disturbances. Ziprasidone (Geodon) is available in an injectable form that we have found to be particularly helpful in TBI patients. 

Sallee, F.R., Kurlan, R., Goetz, C.G., Singer, H., Scahill, L., Law, G., Dittman, V.M., and Chappell, P.B. (2000a) Ziprasidone treatment of children and adolescents with Tourette s syndrome a pilot study. J Am Acad Child Adolesc Psychiatry 39 292—299. 

Receptor-Binding Studies. Among the newer atypical antipsychotics, ziprasidone (Geodon) has a distinctive pharmacological profile ( Fig. 5-2). Binding studies indicate that ziprasidone has a high affinity for D 2 receptors, approximately equal to that of risperidone. In vitro, ziprasidone ... 

Ziprasidone s pharmacokinetics permit rapid and predictable dose adjustment, with metabolites that are considered to be clinically inactive ( 134). The results of PET pharmacokinetic and pharmacodynamic studies indicate that a twice daily dosage regimen is appropriate. 

In one double-blind, randomized, placebo-controlled study, patients were given a daily dose of 40 or 120 mg ziprasidone or placebo for 28 days in 132 patients ( 136). There was a statistically significant improvement in psychotic symptoms versus placebo in the 120 mg/day ziprasidone group as measured by the total BPRS and the CGI scores. Evaluations for parkinsonian symptoms, akathisia, abnormal movements, and sedation did not reveal any notable treatment effects. No significant differences existed between drug and placebo in the total number of adverse events, laboratory test abnormalities, or more serious adverse events. Thus, this study documented that 60 mg ziprasidone twice daily was an effective strategy with negligible risks. 

A number of patients have been exposed to clozapine for several years and TD has not developed. Studies have also investigated patients with TD who were switched to clozapine for periods of 3 weeks to 6 months (461, 462, 463 and 464). Some appeared to improve, but these findings are difficult to interpret because control groups would be needed to demonstrate conclusively that clozapine does not cause TD. Theoretically, if clozapine does not cause acute EPS, then it should not cause TD. Other novel agents such as risperidone, olanzapine, quetiapine, and ziprasidone await longer term exposure to assess their propensity to induce TD. Thus, we agree with Casey, who wrote it is possible that compounds associated with a low rate of EPS may also produce less TD, but prospective studies are needed to confirm this premise (465). 

Preclinical studies of ziprasidone indicate that it also has a low propensity to induce EPS, which was confirmed in subsequent phase II and III studies. Furthermore, the motor symptoms evoked by ziprasidone were seldom sufficiently troublesome to warrant anticholinergic medication. In one phase III trial, not more than 25% of patients receiving 160 mg/day were prescribed an anticholinergic at any time during the 6-week treatment period. These results indicate that therapeutic doses of ziprasidone not only induce a low incidence of acute EPS, but when they occur, they are often mild and do not require antiparkinsonian medication (137). 

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. 

A kinetic study in which ziprasidone (40 mg/day) or placebo were co-administered with a second-generation oral contraceptive has provided evidence that ziprasidone is unlikely to interfere with oral contraception (350). 

There has been one comprehensive meta-analysis including over 80 studies and over 30 000 patients (814). A meta-analysis of trials of neuroleptic drugs showed the following mean weight gains in kg after 10 weeks of treatment clozapine, 4.5 olanzapine, 4.2 thioridazine, 3.2 sertindole, 2.9 chlorpromazine, 2.6 risperidone, 2.1 haloperidol, 1.1 fluphenazine, 0.43 ziprasidone 0.04 molindone, —0.39 placebo, —0.74... 

In a placebo-controlled, open-label study in 25 healthy subjects there were no changes in serum lithium concentration or renal lithium clearance when ziprasidone (40-80 mg/day) was added for 7 days (640). 

Brook S, Lucey JV, Gunn KP. Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group. J Clin Psychiatry 2000 61(12) 933-41. 

Goff DC, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner KD, Law CG, Ko GN. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 1998 18(4) 296—304. 

Patients taking olanzapine (mean dose 12.6 mg/day n = 71) had significantly more weight gain than those taking ziprasidone (mean dose 135.2 mg/day n = 55) in a 6-month, randomized, double-blind, multicenter study of 126 patients (63c). The mean changes in body weight and body mass index were 5.0 kg and 1.3 kg/m2 respectively with olanzapine and -0.8 kg and -0.6 kg/m2 with ziprasidone. 

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