Improved Sleep Continuity and Increased Slow Wave Sleep and REM Latency During Ziprasidone Treatment: A Randomized, Controlled, Crossover Trial of 12 Healthy Male Subjects

Stefan Cohrs, M.D.; Andreas Meier, M.D.; Anna-Catharina Neumann, M.D.; Wolfgang Jordan, M.D.; Eckart Rüther, M.D., Ph.D.; and Andrea Rodenbeck, Ph.D.

Objective: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D₂) 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.

(J Clin Psychiatry 2005;66:989-996)

Received Nov. 15, 2004; accepted Jan. 18, 2005. From the Department of Psychiatry and Psychotherapy, Georg-August-University of Göttingen, Germany.

No external funding for the study was received.

Dr. Cohrs has received grant/research support from and has participated in speakers/advisory boards for AstraZeneca. Dr. Rüther has received grant/research support and/or honoraria from and/or has participated in speakers/advisory boards for AstraZeneca, Pfizer, Lilly, Janssen, Bristol-Myers Squibb, Organon, Lundbeck, and Wyeth. Drs. Meier, Neumann, Jordan, and Rodenbeck report no financial affiliation or other relationship relevant to the subject matter of this article.

The authors are grateful to the dedicated staff of the Sleep Medicine Center of the Department of Psychiatry and Psychotherapy, University of Göttingen, Germany, including Roswitha Bianco, Iris Bossmann, Brigitte Marxen, and Andreas Müller-Struck.

Corresponding author and reprints: Stefan Cohrs, M.D., Department of Psychiatry and Psychotherapy, von-Siebold-Strasse 5, 37075 Göttingen, Germany (e-mail: scohrs@gwdg.de).