Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo

Background: The study aimed to determine the effects of the atypical antipsychotic agent, olanzapine, on the polysomnogram in healthy subjects. We predicted that olanzapine, via serotonin2C (5-HT2C) receptor blockade, would increase slow-wave sleep (SWS). Methods: We studied the effects of single evening doses of olanzapine (5 mg and 10 mg orally) on the polysomnogram of 9 healthy male volunteers, using a placebo-controlled, double-blind, cross-over design. Results: Compared to placebo, the 5-mg and 10-mg doses of olanzapine significantly increased SWS, sleep continuity measures, and subjective sleep quality. In addition, 10 mg of olanzapine suppressed rapid eye movement (REM) sleep and increased REM sleep latency. Conclusions: Olanzapine (5 mg and 10 mg) produced substantial (59.1% and 83.3%) and highly significant dose-related increases in SWS in humans probably via blockade of brain 5-HT2C receptors. 5-HT2C receptor antagonism may account for some of the therapeutic and adverse effects of olanzapine therapy