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Sammanfattning

Ziprasidone, one of the new second-generation antipsychotics, was introduced in Denmark in March 2002. The efficacy of the new second-generation antipsychotics, including ziprasidone, on positive, negative and affective symptoms of schizophrenia is almost at the same level. However, the side-effect profiles of the compounds have substantial and significant differences. Ziprasidone can be administered both perorally and intramuscularly and is indicated for the treatment of schizophrenia and other psychotic disorders, and for the treatment of excitation and agitation. The peroral ziprasidone has been studied in schizophrenia and schizoaffective disorder, the intramuscular (IM) formulation in agitated psychotic patients. Newer second-generation antipsychotics are recommended as first-line drugs to incident-schizophrenic patients and schizophrenic patients with a short duration of disorder, and to patients with side effects, e.g., EPS or lack of efficacy of other antipsychotics. It binds with high affinity to central dopamine (DA) and serotonin (5HT) receptors. It has moderate affinity for a 1-adrenoceptors and histamine H1 receptors. The affinities for all other receptors are negligible. Ziprasidone also has moderate affinities for the 5HT and noradrenaline transporters, inhibiting the reuptake of these neurotransmitters. When taken with a fat-containing meal, its absolute bioavailability is 60%. Ziprasidon is metabolised primarily in the liver by the aldehyde oxidase and the cytochrome isozyme (CYP3A4), whereas it has no significant interactions with the isozymes across the clinical dose range. Ziprasidone has a significant higher efficacy than a placebo in acute schizophrenia and schizoaffective disorder with effects on positive, negative and affective symptoms. Ziprasidone is as effective as haloperidol in these disorders. In a long-term study it was shown to be effcctive in preventing acute relapses of schizophrenia. Ziprasidone has a low risk of EPS, and, generally, the side effects were of mild to moderate severity. Common side effects with higher incidences than those of a placebo were somnolence, nausea and dyspepsia in the short-term studies and insomnia in the long-term study. Unlike the other atypical antipsychotics, it appeared to be weight neutral in both short-term and long-term studies. Ziprasidon may prolong the corrected QT interval in some patients. Thus, it may be contraindicated in a few patient groups.

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