Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission.

OBJECTIVE

Ziprasidone is an atypical antipsychotic with a high ratio of 5-HT(2A) to D(2) receptor antagonism. It is also an agonist at 5-HT(1A), which has been shown in rats to increase dopamine in prefrontal cortex. The objective of this study was to probe the dopamine agonist and antagonist pharmacodynamic properties of ziprasidone in youth.

METHODS

A single-dose, open-label study was conducted in 24 youths, 7 to 16 years of age, with Tourette syndrome or chronic tic disorder. Ziprasidone oral suspension (40 mg/mL) was given to achieve 0.2 to 0.3 mg/kg. Patients were subsequently assessed for serum ziprasidone, serum prolactin, and eye blink rates.

RESULTS

Serum ziprasidone peaked 4 hours postdose. Prolactin (baseline mean 7.2 ng/mL, 95% confidence interval [CI] 5.2-9.2) peaked at 4 hours (mean 27.5 ng/mL, 95% CI 22.6-32.3). Eyeblink rates per 5 minutes (baseline mean 60, 95% CI 42-79) peaked at 6 hours (mean 74, 95% CI 52-96).

CONCLUSIONS

Ziprasidone acutely blocks dopamine transmission, as indicated by increased prolactin levels, and, in a delayed fashion, appears to stimulate dopaminergic transmission, as indicated by the increase in spontaneous eye blinks. The mechanism of dopaminergic stimulation is presumed to be indirect, via 5-HT(1A) agonism.