Sleep Laboratory Studies on the Single-Dose Effects of Serotonin Reuptake Inhibitors Paroxetine and Fluoxetine on Human Sleep and Awakening Qualities

Abstract

Paroxetine is a novel antidepressant drug with selective serotonin (5-HT) reuptake inhibitory properties. In a double-blind placebo-controlled crossover sleep laboratory study the single-dose effects on objective and subjective sleep and awakening qualities were investigated after paroxetine 20, 30 and 40 mg morning doses (PX 20, 30, 40), paroxetine 30 mg evening dose, fluoxetine 40 mg morning dose (FX 40) and placebo in 18 healthy young volunteers. The drugs were orally administered in 2-wk intervals. In addition to each drug night, the adaptation night and washout night were recorded. Polysomnographic investigations (10:30 p.m. to 6:00 a.m.) showed a delayed sleep onset only after the morning intake of paroxetine, PX 40 being statistically different from placebo. Total sleep time and sleep efficiency deteriorated under morning PX 30, PX 40 and evening PX 30 as compared to placebo. The nocturnal wake time and sleep stage 1 increased under the paroxetine. Rapid eye movement (REM) reduction (min and %) occurred dose dependently after all paroxetine doses, but the REM latency was lengthened only after the morning intake. The suppressant effect on REM sleep is characteristic for antidepressants and was still significant in the washout nights following PX 40 and evening PX 30. The only statistically relevant finding under 40 mg fluoxetine referred to the increase of REM latency in both drug and washout nights. In contrast to objective results, subjective sleep quality remained generally unchanged. Attention, concentration and reaction performance improved under paroxetine as compared to baseline. The deterioration of well-being under PX 40 might be related to the appearance of drowsiness and nausea. Blood pressure and pulse rate were unaffected.

Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects

“…At high doses, the power of the low frequencies increased, and the alpha and beta changes disappeared. Similar findings have been reported previously by Saletu et al [10].…”

Human Taste Thresholds Are Modulated by Serotonin and Noradrenaline

“…Pharmacokinetic study of SSRIs and NARIs show that peak drug plasma concentrations occur at 1-2 h (Finley, 1994;Hendershot et al, 2001), whereas peak CNS effects, such as sleep disturbance or motor effects, occur 6 -8 h after administration (Saletu et al, 1991;Hindmarch, 1997;Loubinoux et al, 2002). This suggests that at 2 h, plasma drug levels are much greater than brain drug levels and peripheral effects may be more pronounced than central effects.…”

Changes of Sleep Architecture, Spectral Composition of Sleep EEG, the Nocturnal Secretion of Cortisol, ACTH, GH, Prolactin, Melatonin, Ghrelin, and Leptin, and the DEX-CRH Test in Depressed Patients during Treatment with Mirtazapine

“…Substances with nonselective action on the serotoninergic system, for example, 5-HT reuptake inhibitors (SSRIs), often induce disturbed sleep as an increase in intermittent wakefulness, whereas SWS is largely unaffected by these substances (Saletu et al, 1991;Rush et al, 1998). No alterations of the spectral composition of sleep EEG were found during subchronic treatment with paroxetine in healthy subjects (Röschke et al, 1997).…”