Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects.

OBJECTIVE: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. METHOD: The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. RESULTS: Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. CONCLUSION: Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.

Ziprasidone decreases cortisol excretion in healthy subjects.

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) microg during N1 and by 10.8 (95% CI 5.7, 15.8) microg 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) microg after N1 and by 12.1 (95% CI 2.8, 21.4) microg 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.