Chlorpromazine and human sleep

Abstract

The aim of this study was to examine human physiological sleep profiles, including the amount and distribution of electroenoephalographic (EEG) stages of sleep, variations in specific frequency bands in the EEG spectrum and certain phasic phenomena such as movement arousals, sigma spindles and rapid eye movements, following oral administration of a moderate dose (150 mg) of chlorpromazine (CPZ) to 12 young male volunteers. At this dose level the drug had few systematic effects on sleep, although it did reduce the latency of onset of stage REM and the number of movement arousals, while increasing the amount of slow-wave (SW) sleep. These effects persisted during the post-medication recovery night, but at no time was there any systematic change in the total amount or percent of REM sleep, the duration of the REM-to-REM cycle, the average length of REM episodes or the density of rapid eye movements during stage REM. Frequency analysis of EEG revealed that CPZ produced a trend toward increased fast (beta) activity recorded from pre-central placements during stage REM, and reduced density of sigma spindles in stage 2 sleep. Thus, for the most part, a single moderate dose of CPZ left the tonic, phasic and sequential properties of the sleep cycle unaltered. These results confirm previous investigations showing that for small to moderate clinical doses, CPZ invariably enhances SW sleep and reduces the frequency of movement arousals. On the other hand, the effect of the drug on stage REM apparently depends on dose. Small doses potentiate REM sleep or accelerate its onset, whereas larger doses either reduce stage REM or leave it unaffected. Several authors have pointed out that most hypnotic agents cause substantial alterations of the sleep profile, and that their withdrawal can cause profound disruption of sleep and marked clinical disturbance. It also has been suggested that there exists a relation between drug dependency and the degree of initial REM suppression caused by a drug. The finding confirmed by the present study that clinical doses of CPZ cause mild sedation, and enhanced SW sleep without any significant modification of REM, sleep, indicates that CPZ has features which may recommend it as a standard hypnotic.