Methods and Findings in Experimental and Clinical Pharmacology
Vol. 25, Suppl. A, 2003
ISSN 0379-0355
Copyright 2003 Prous Science, S.A.
CCC: 0379-0355/2003
http://www.prous.com

Ziprasidone: A Promising Alternative in the Treatment of Schizophrenia

M. Madrigal, T. Díez and M. Cano

Medical Unit, Pfizer S.A.

Schizophrenia is a frequent, debilitating and devastating illness for patients, families and caregivers, with a marked higher morbidity and mortality rate than that observed in the general population. Ziprasidone is a new atypical antipsychotic drug with a pharmaceutical profile that is different from previous antipsychotics. As with other atypical antipsychotics, it acts as both a 5HT_2A and D₂ receptor antagonist, while in vitro it demonstrates an affinity for the former that is approximately 11 times greater. This favors its antipsychotic efficacy and lowers the risk of extrapyramidal symptoms. Ziprasidone is also a potent 5HT_2c and 5HT_1D receptor antagonist, a potent 5HT_1A receptor agonist and it inhibits serotonin and noradrenaline reuptake, which could have additional clinical benefits such as improved positive and negative symptoms, anxiolytic activity and a potential antidepressant effect. The affinity of ziprasidone for H₁ and a1 receptors is moderate and for M₁ practically insignificant.

Oral ziprasidone at a dose of 80-160 mg/day is effective for long and short-term treatment of schizophrenia. The availability of an intramuscular injection of ziprasidone (10 and 20 mg) allows rapid control of agitation in acute psychoses and an optimum transition to oral therapy without having to alter the active substance. Compared to other therapeutic alternatives, ziprasidone appears to have an efficacy comparable to risperidone, olanzapine, haloperidol and amisulpride. Ziprasidone improves depressive symptomatology when patients present with depressive symptoms at the start of treatment.

Ziprasidone is a safe drug and its unique tolerability profile offers major advantages in the long-term treatment of schizophrenia. The overall incidence of adverse events (AEs) is considerably less than with risperidone or haloperidol and fewer withdrawals due to AEs have been reported. Unlike olanzapine, it does not induce metabolic alterations (weight, glycemic and lipid profile) and compared to risperidone and haloperidol it does not cause an increased production of prolactin. The risks of motor disturbances with ziprasidone is less than that observed with haloperidol or risperidone. The cardiovascular risks with ziprasidone do not appear to be any different from other available antipsychotics. Evidence has shown that its effect on the QT interval is mild and no cardiac AEs have been reported nor any torsade de pointes episodes during treatment or after overdosing. Furthermore, there have there been no reports of an increase in global mortality nor the incidence of sudden cardiac death or syncope.

Considering its safety and efficacy profile, ziprasidone appears to be a promising alternative therapy for the treatment of schizophrenia.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 25, Suppl. A, 2003
ISSN 0379-0355 Copyright 2003 Prous Science, S.A. CCC: 0379-0355/2003 http://www.prous.com