Ziprasidone controlled studies

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. 

The effect of steady-state carbamazepine administration on the steady-state pharmacokinetics of ziprasidone has been studied in 25 healthy young adults, in a randomized, placebo-controlled study (112). Carbamazepine caused small reductions in ziprasidone AUCo i2 and Cmax (36% and 27% respectively). The authors concluded that carbamazepine had increased ziprasidone clearance by induction of CYP3A4. 

In a randomised, placebo-controlled study, 14 healthy subjects were given a 40-mg dose of ziprasidone before and after taking ketoconazole 400 mg daily for 6 days. It was found that ketoconazole increased the AUC and maximum serum levels of ziprasidone by 33% and 34%, respectively. This modest rise in levels probably occurs because ketoconazole inhibits the cytochrome P450 isoenzyme CYP3A4 by which ziprasidone is metabolised. However, it was concluded that the increase is not clinically relevant. No special precautions would therefore seem to be needed on concurrent use. 

A randomised, placebo-controlled study in 25 healthy subjects taking lithium carbonate 450 mg twice daily for 15 days, found that ziprasidone 20 mg twice daily on days 9 to 11, followed by 40 mg twice daily on days 12 to 15 caused only a small increase in the steady-state serum-lithium levels (14% compared with 11% in the placebo group). A 5% reduction in renal clearance was seen in the ziprasidone group and a 9% reduction was seen in the placebo group. These differences were neither statistically nor clinically significant. No special precautions would therefore seem to be necessary if ziprasidone is given to patients taking lithium. 

Controlled studies A QTc study of three doses of ilopeiidone was conducted in the presence of metabolic inhibitors of CYP2D6 and/or CYP3A4 with a comparison to quetiapine and ziprasidone [157 ]. Uoperidone BID produced mean changes in QTcF comparable with ziprasidone and quetiapine. A higher single daily dose of Uoperidone... 

Controlled Studies A study of pooled data from nine randomised, double-blind, placebo-controlled, acute studies of ziprasidone in bipolar mood disorder and schizophrenia was conducted [279 -]. The risk of discontinuation due to adverse events or >7% weight gain was not different to placebo. The risk for akathisia was significantly higher for mood disorders and the risk of extrapyramidal symptoms and somnolence (dose dependent) was significantly higher for both mood disorders and schizophrenia compared to placebo. 

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). 

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. 

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). 

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. 

Ziprasidone is apparently well tolerated, with a limited potential to cause extrapyramidal adverse effects or weight gain (4). Out-patients who partly respond to conventional antipsychotic drugs, risperidone, or olanzapine may have improved control of psychotic symptoms after switching to ziprasidone, according to the results of a reanalysis of 6-week, multicenter, randomized, open, parallel-group studies in patients with schizophrenia who had previously taken conventional antipsychotic drugs (n = 108), olanzapine (n = 104), or risperidone (n = 58) these results have been published in two different journals (5, 6). 

In an open 12-week study of ziprasidone in 12 patients with Parkinson s disease and psychosis, two withdrew because of adverse effects one had increased diurnal sedation on day 5 and the other had deterioration of gait at 1 week (7C). The other 10 patients reported significant improvement in psychiatric symptoms and no deterioration in motor symptoms. The small sample size and lack of a control group precluded definitive conclusions. 

Ziprasidone is oxidatively metabolized by CYP3A4, but it does not inhibit CYP3A4 or other isoenzymes at clinically relevant concentrations. The effect of ketoconazole 400 mg qds for 6 days on the single-dose pharmacokinetics of ziprasidone 40 mg has been evaluated in an open, placebo-controlled, crossover study in healthy volunteers... 

Miceli JJ, Smith M, Robarge L, Morse T, Laurent A. The effects of ketoconazole on ziprasidone pharmacokinetics—a placebo-controlled crossover study in healthy volunteers. Br J Clin Pharmacol 2000 49(Suppl. 1) 71S-6S. 

Conventional antipsychotics improve symptoms of hyperactivity and impulsivity, but may have negative effects on learning and cognitive functioning as well as extrapyramidal side effects (e.g., dystonia and tardive dyskinesia) that limit their usefulness. The atypical antipsychotics risperidone, olanzapine, quetiapine, and ziprasidone have been used to control severe aggression in refractory cases of ADHD, particularly if conduct disorder or bipolar disorder coexists. More studies are needed to clarify their place in therapy. ... 

Other atypical antipsychotics commonly prescribed for treatment of autism include olanzapine, quetiapine, ziprasidone, and clozapine (Oswald and Sonenklar, 2007). Placebo-controlled trials of these agents in ASD populations have not been reported, with the exception of a small pilot study of olanzapine in which three of six children treated with olanzepine were rated as responders, compared to one of five in the placebo group (Hollander et al., 2006b). Open-label studies (reviewed by... 

Keck PE jr. Reeves KR, Harrigan EP et al. Ziprasidone in the short-term treatment of patients with schizoaffective disorder results from two double-blind, placebo controlled, multicenter studies. J Clin Psychopharmacol 2001 21 27. 

In a placebo-controlled, crossover study, 18 women taking an oral contraceptive (ethinylestradiol/levonorgestrei 30/150 micrograms) for at least 3 months were also given ziprasidone 20 mg twice daily for 8 days. The only change in the pharmacokinetics of the two steroids was an approximately 30-minute increase in the time to maximum plasma concentration of the levonorgestrel, but this was not considered to be clinically significant. No adverse effects occurred. It was concluded that combined use is safe and that ziprasidone does not affect the efficacy of this oral contraceptive and is also unlikely to affect the metabolism and therefore effieaey of other similar contraceptives. 

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