Ziprasidone is a novel
antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical
antipsychotics. In preclinical studies,
ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of
schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. The
drug has been administered orally to >300 patients with an acute exacerbation of
schizophrenia or
schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily at dosages of between 80 and 160 mg/day,
ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study,
ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that
ziprasidone 160 mg/day has similar efficacy to
haloperidol 15 mg/day.
Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic
schizophrenia who were treated for up to 1 year. In addition, significantly more
ziprasidone than
haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic
schizophrenia. In general, oral
ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the
drug has a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight.
Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The
drug does not appear to be associated with sustained elevation of plasma
prolactin levels. Preliminary data indicate that long-term oral
ziprasidone treatment is well tolerated.
Ziprasidone is the only novel
antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular
ziprasidone was effective and well tolerated in patients with acute agitation associated with
psychosis. In addition, intramuscular
ziprasidone reduced agitation scores by a significantly greater extent than
haloperidol in a study involving patients with acute agitation associated with
psychosis.
CONCLUSIONS: