Effects of olanzapine, risperidone and haloperidol on sleep after a single oral morning dose in healthy volunteers

Abstract

Objectives To compare the effects of typical and atypical antipsychotic drugs on sleep activity and subjective sleep quality. Design Randomised, double-blind, placebo-controlled, four-period cross-over, clinical trial was used to evaluate the effects of active treatments on objective and subjective sleep variables. Setting Sleep laboratory evaluation. Participants Twenty healthy young volunteers, both sexes. Interventions Single oral morning administrations of olanzapine 5 mg, risperidone 1 mg, haloperidol 3 mg and placebo. Measurements and results Five polysomnographic nights were evaluated: one control night and one after each intervention. Significant increase in total sleep time, sleep efficiency, slow wave sleep (SWS) and rapid eye movement (REM) sleep with decreases in wake time were observed after olanzapine. Decreases in wake time, REM sleep and stage shifts together with increases in stage 2 were obtained after risperidone. Haloperidol showed only a tendency to increase sleep efficiency and stage 2 and to decrease wake time. Olanzapine showed decreases in power density in frequencies higher than 10 Hz during all sleep stages and in frequencies lower than 5 Hz range in SWS; decreases in the dynamics of spindle frequency activity (SFA) in the second and fourth non-rapid eye movement (NREM) episodes were also obtained. Risperidone presented increases in the 3.6-10.8 Hz frequency range in NREM sleep stages and in stage 2. Haloperidol also showed increases in NREM sleep stages and in stage 2, but these were in frequencies higher than 10 Hz, with increases in the dynamics of SFA in the first NREM episode. Only a significant improvement in subjective sleep quality was observed after olanzapine. Conclusions Antipsychotics showed different sleep changes as their neurochemical profiles were distinct. These changes were observed even when the drug was administered 15 h before going to bed.

Influence of Antipsychotic Agents on Heart Rate Variability in Male WKY Rats: Implications for Cardiovascular Safety

“…This discrepancy might be a result of its more complex pharmacological action [48]. Haloperidol, however, has been shown to have a sleep-promoting effect, concordant with our results [24]. Considering the sleep-disturbing effect, clozapine appears to be more hazardous.…”

“…Since the acetylcholine and monoamines are all known to be involved in the regulation of sleep, these drugs are expected to modify the sleep-wake cycle [22,23,24]. Along the sleep-wake cycle, sympathetic and parasympathetic activity fluctuates cyclically, with higher vagal activity during quiet sleep (QS) and higher sympathetic activity during wakefulness and paradoxical sleep (PS) [25,26].…”

Waking and Sleep Electroencephalogram Variables as Human Sleep Homeostatic Process Biomarkers after Drug Administration

“…It has also been found that morning doses of olanzapine produce a more striking SWS enhancement than evening administrations [29] . Significant increases in SWS were also elicited in our study [15] . However, since the main EEG biomarker of sleep homeostasis is the exponential decline of SWA but not the SWS [2] , the time course of this measure was calculated.…”

“…In order to assess this objective, data coming from the study of Giménez et al [15] were used. In this study significant hypnotic effects of olanzapine oral morning administration were observed.…”

Multinomial Logistic Functions in Markov Chain Models of Sleep Architecture: Internal and External Validation and Covariate Analysis

“…The latter have made large investments in this research field, trying to develop safer and more effective drugs able to regulate the sleep-wake alternation. But it is of particular importance that the therapeutic interventions also maintain the physiological sleep architecture (2,3), which is a physiologically relevant description of the sequence of sleep stages (REM, slow-wave sleep, awake, etc.) coming one after the other during nighttime.…”