Reduced cortisol excretion in healthy subjects under treatment with ziprasidone

Aims: To determine the influence of the atypical antipsychotic ziprasidone on cortisol excretion. Methods: In a double-blind, placebo-controlled, randomized cross-over study 11 healthy male subjects were studied two times for two consecutive nights (N1, standard sleep conditions; N2, acoustic stress) 5 days apart. Placebo or ziprasidone 40mg was administered orally 2 hours before bedtime on N1 and N2. Urine was collected during three fractionated collection periods for determination of cortisol concentrations. Results: ANOVA showed a significant reduction of cortisol excretion (p<0.002) under ziprasidone during the night. Ziprasidone reduced total amount of cortisol excretion in comparison to placebo by 4.9 (95% CI 3.3, 6.5) μg during N1 and by 10.8 (95% CI 5.7, 15.8) during N2. This effect was still measurable in the morning hours (p<0.02), when ziprasidone reduced cortisol excretion in comparison to placebo by 5.8 (95% CI –2.8, 14.4) μg after N1 and by 12.1 (95% CI 2.8, 21.4) μg after N2. A significant intervention x condition interaction (p<0.02), was found. The significant increase in cortisol excretion under acoustic stress observed with the placebo treatment was absent under the treatment with ziprasidone. Conclusion: The significant reduction of nocturnal cortisol excretion following ziprasidone reflects a decreased activity of the HPA-axis in healthy subjects.