Ziprasidone: from pharmacology to the clinical practice. One year of experience

More than a year after the marketing of the atypical anti-psychotic ziprasidone, data from research studies and clinical practice have provided a fair amount of useful information for its practical use in the treatment of schizophrenia. Its pharmacodynamical characteristics and the results from clinical trials with a flexible dose seem to justify the need to administer doses in a range higher than what was initially foreseen, with an initial minimum of 120 mg per day and a fast titulation up to 160 mg per day. Such doses make it possible to achieve sufficient plasma concentrations to occupy at least 60 % of the D2 receptors from which the anti-psychotic effect derives. Moreover, its anti-depressive activity and its non-sedative profile have been confirmed, with a favorable effect on attention and other cognitive functions of the patient, according to its high affinity for 5HT1A and D1 receptors and the inhibition of serotonin and noradrenaline re-uptake. Finally, the low affinity of this drug for alpha-adrenergic, histaminergic and muscarinic receptors favors a good tolerability profile, with a neutral effect on weight, and a lack of anti-cholinergic effects. Results from different clinical trials show that the use of doses in the higher range is associated to a faster and more pronounced clinical improvement without adding a higher risk of adverse events.