Ziprasidone decreases cortisol excretion in healthy subjects

Abstract

Aims To determine the influence of the atypical antipsychotic ziprasidone on cortisol excretion. Methods In a double-blind, placebo-controlled, randomized cross-over design 11 healthy male subjects were studied twice for 2 consecutive nights (N1, undisturbed sleep conditions; N2, exposure to acoustic stress) 5 days apart. Placebo or ziprasidone 40 mg was administered orally 2 h before bedtime on N1 and N2. Urine was collected during three fractionated collection periods (evening; night; morning) for the later determination of cortisol concentrations by standard radioimmunoassays. Results Ziprasidone decreased the total amount of cortisol excreted by 4.9 (95% CI 3.3, 6.5) mu g during N1 and by 10.8 (95% CI 5.7, 15.8) mu g during N2 (P < 0.002). This effect was still detectable in the morning (P < 0.02), with decreases of 5.8 (95% CI -2.8, 14.4) mu g after N1 and by 12.1 (95% CI 2.8, 21.4) mu g after N2. The effect subsided in the evening. A significant intervention-condition interaction (P < 0.02), was found. The significant increase in cortisol excretion during acoustic stress observed with placebo was absent after treatment with ziprasidone. Conclusions The significant decrease in nocturnal cortisol excretion following ziprasidone reflects a decreased activity of the HPA-axis in healthy subjects. This effect may be an important contributor to the mode of action of ziprasidone in different patient populations, particularly in the treatment of depression and in cognitive impairment in schizophrenia.