Studies on the Modulation of the Sleep-wakefulness Continuum in Man by Fluoxetine, a 5-HT Uptake Inhibitor

The effects of an inhibitor of the uptake of 5-hydroxytryptamine (5-HT) fluoxetine (20, 40 and 60 mg), on nocturnal sleep and on alertness during the day, were studied in healthy adults. Fluoxetine reduced the total sleep time and the duration of rapid eye movement (REM) sleep and increased awake activity and stage 1 (drowsy) sleep during the night. Daytime sleep latencies were longer after fluoxetine but, paradoxically, the subjects felt more drowsy and coding ability was impaired. It is considered that the alerting effect of fluoxetine in man is most likely related to modulation of 5-HT-mediated transmission, whereas suppression of REM sleep is a nonspecific effect which arises when the balance of monoaminergic and cholinergic influences is disturbed. It is suggested that the serotonergic system has a pervasive influence throughout the sleep-wakefulness continuum, in contrast with some other neurotransmitter systems, which may be more concerned with the subtle manifestations of vigilance.