Zeldox (ziprasidone) is a new atypical antipsychotic with similar efficacy to that of the other medicinal products in the same group, e.g. olanzapine, quetiapine and risperidone. Safetywise, ziprasidone displays the same low level of extrapyramidal effects as the other atypical antipsychotics. On the other hand, there is a risk of QT prolongation, which is why caution should be shown in prescribing ziprasidone for patients who have known heart disease. Ziprasidone costs about the same as olanzapine and quetiapine when their defined daily doses are compared.
Zeldox (ziprasidone) is a new atypical antipsychotic for the treatment of schizophrenia. The product has been marketed in Denmark since 4 March 2002 in the form of 40, 60 and 80 mg capsules and as a solution for injection 20 mg/ml for i.m. administration.
Ziprasidone has a high affinity for serotonin type 2A and dopamine type 2 receptors and an antagonistic activity which is believed to mediate, in part, its antipsychotic effect. The drug also demonstrates a moderate affinity for histamine receptors and a negligible affinity for muscarinic receptors.
The efficacy of antipsychotics can be assessed on a number of different rating scales; these scales generally rate drugs by their effect on the positive, negative (including depressive) and cognitive symptoms of schizophrenia.
In several placebo-controlled studies, ziprasidone was found to be efficacious in the treatment of positive, negative (including depressive) and cognitive symptoms at doses of 80 mg to 160 mg/day. A few studies indicate that many patients can be kept on a maintenance dose of 40 mg/day.
Few studies have compared different treatment regimens. In one comparative study with ziprasidone 40-200 mg/day, haloperidol 15 mg/day displayed a marginally better effect on positive symptoms, but haloperidol induces several extrapyramidal effects. In another study, ziprasidone 80-160 mg/day produced the same effect on both positive and negative symptoms as olanzapine 5-15 mg/day. The same result can be found in meta-analyses, which also include risperidone 10 mg/day and the other atypical antipsychotics, all of which seem to display the same efficacy.
Like the other atypical antipsychotics, ziprasidone is apparently efficacious in the treatment of patients in whom negative (including depressive) or cognitive symptoms are dominant.
The recommended starting dose for patients is 40 mg ziprasidone twice daily. The capsules must be taken with food, which increases the bioavailability of the drug.
In a randomised, controlled study, i.m. administration of 2, 10 or 20 mg ziprasidone no more than three times daily at intervals of at least four hours had a significant effect of 10 and 20 mg on the BARS (Behavioural Activity Rating Scale) and on positive and negative symptoms in agitated patients with schizophrenia. I.m. ziprasidone 5-20 mg also displayed efficacy equal to that of i.m. haloperidol 2.5-10 mg in a randomised study.
Adverse drug reactions
The most common adverse reactions to ziprasidone use are somnolence and nausea.
In studies, ziprasidone was seen to induce a mild to moderate QT-interval prolongation of 30-60 msec in 10-15% of patients and >60 msec in a few patients. A prolongation of QT interval was seen in 7.5% of the patients in the placebo group. No increased risk of torsade de pointes or sudden death has been observed. Consequently, ziprasidone is contraindicated in the case of known QT-interval prolongation, recent AMI, incompensated morbus cordis, and arrhythmias treated with Class Ia and III antiarrhythmic drugs (QT-prolonging). Caution should also be exercised when treating patients with any other type of heart disease. In certain cases, taking an ECG should be considered before treatment is started.
The incidence of extrapyramidal effects such as parkinsonism, dystonia and akathisia is the same as it is with the other atypical antipsychotics, i.e. occurring in 1-10%.
According to one meta-analysis, ziprasidone 40-160 mg/day caused minimal weight gain over one year compared with a number of other antipsychotics; however, this observation was based on extrapolated data. Elevated prolactin levels were observed in a few patients in long-term treatment, but levels returned to normal without discontinuation of ziprasidone treatment. No increase in total cholesterol or glucose has been seen in treatment with ziprasidone.
Ziprasidone should be avoided in combination with other medical products that prolong the QT interval, e.g. Class Ia or III antiarrhythmic drugs, since there is a risk of an additive effect. However, there are no studies that shed light on this problem.
Ziprasidone is metabolised partly in the liver, and in vitro studies indicate that ziprasidone inhibits CYP2D6 and CYP3A4, which is why care should be taken in the case of other medicinal products that are metabolised in these isoenzyme systems.
Cost per day (prices as at 18 March 2002)
||Cost (in DKK) per DDD|
Additional information is available from the summary of product characteristics published by the Danish Medicines Agency (Danish only).
Last modified: March 4th 2002