The atypical antipsychotic ziprasidone demonstrates polysomnographic features of an antidepressant

Ziprasidone, an atypical antipsychotic, is a potent dopamine (D2) and serotonin (5 HT 2A/C) receptor blocker, has agonistic properties at the 5HT1A receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep.

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. 12 healthy male subjects were randomized to receive ziprasidone 40mg or placebo twice during two consecutive nights (N1, standard sleep conditions; N2, acoustic stress) 5 days apart.

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. decreased percentage REM and REM density, and profoundly increased REM latency.

Ziprasidone’s effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients. 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 5HT–2C antagonism, 5HT–1A agonism, and serotonin and norepinephrine reuptake inhibition.