The Effects of Fluoxetine on the Polysomnogram of Depressed Outpatients: A Pilot Study

Abstract

The effects of fluoxetine (FLU) and its active metabolite, norfluoxetine (NFLU), on the polysomnogram (PSG) of nine depressed outpatients (eight with major depression; one with bipolar II, depressed phase disorder) were investigated by contrasting PSG values prior to treatment and during administration of FLU. The PSG changes were correlated with daily dose, cumulative dosage, single serum concentrations, and the total area under the serum concentration curve (AUC) of both FLU and NFLU.KEY WORDS: Fluoxetine; Norfluoxetine; Polysomnography; Serotonin; Depression Fluoxetine (FLU)-a potent, specifIc, serotonin reup take inhibitor-is an effective treatment for major depression (for a review, see Depression Guideline Panel, 1993). Serotonin affects the regulation of the sleep-wake cycle. It plays a role in the induction and maintenance of sleep as well as the character of sleep stage macro architecture and rapid-eye-movement (REM) sleep expression Oouvet et al. 1989).Fluoxetine reportedly causes a shift toward lighter Fluoxetine clearly increased both stage 1 sleep time and rapid-eye-movement (REM) latency and decreased both percent REM and REM density. With a few exceptions, the cumulative dosage of FLU and the AUC of FLU and NFLU were better predictors of the changes in awake and movement time in the PSG than single-sample concentrations of FLU and NFLU taken at the time of PSG assessment. fNeuropsychopharmacology 10: 85-91, 1994J sleep that is reflected in increases in sleep latency and percentage of non-REM stage 1 sleep and decreases in total sleep time, sleep efficiency, and percentage of non REM stages 3 and 4 sleep (Nicholson and Pascoe 1986;Pastel and Fernstrom 1987;Kerkhofs et al. 1990;Keck et al. 1991;Keck and McElroy 1992). The duration of REM sleep and REM latency, as well as REM density, may also be affected by FLU (Nicholson and Pascoe 1988;von Bardeleben et al. 1989;Nicholson et al. 1989; Bakalian and Fernstrom 1990;Hanzel et al. 1991;Saletu et al. 1991). These effects likely depend upon both the dose and duration of FLU treatment.Changes in polysomnogram (PSG) measures as sociated with chronic FLU treatment in depressed sub jects have been incompletely studied (Schenck et al. 1992). Relationships among PSG measures and serum concentrations of FLU and its active metabolite norflu oxetine (NFLU) have not been previously reported in depressed patients. This pilot study evaluated the effect of FLU and NFLU on PSG measures in a group of medication-responsive depressed outpatients.

State Markers of Depression in Sleep EEG: Dependency on Drug and Gender in Patients Treated with Tianeptine or Paroxetine

“…One important aspect of the REM density is that it is a marker of depression in drug-free subjects and independent of gender (Lauer et al, 1991). It is affected by SSRIs (Hendrickse et al, 1994;Armitage et al, 1995b) in depressed subjects, and by sleep deprivation in healthy controls (Murck et al, 1999) and depressed subjects , but not by tianeptine in depressed subjects, as presented before. A study using REM latency under medication-free condition as a predictor for the response with fluoxetine failed to do so (Heiligenstein et al, 1994).…”

5-HT1A/1B Receptor-Mediated Effects of the Selective Serotonin Reuptake Inhibitor, Citalopram, on Sleep: Studies in 5-HT1A and 5-HT1B Knockout Mice

“…Indeed, in several species and notably the rat (Pastel and Fernstrom, 1987;Ursin et al, 1989;Lelkes et al, 1994;Maudhuit et al, 1994;Neckelmann et al, 1996b), the hamster (Gao et al, 1992), and also in humans (Van Bemmel et al, 1993;Hendrickse et al, 1994), the most consistent action of SSRIs is a reduction of paradoxical sleep (PS), which is sometimes associated with an enhancement of wakefulness (W) and a secondary increase in slow wave sleep (SWS) (Maudhuit et al, 1994;Ursin, 2002). In the same manner, systemic treatment with selective agonists at 5-HT 1A and 5-HT 1B receptors induces an inhibition of PS and an enhancement of wakefulness, notably in rodents (Dzoljic et al, 1992;Tissier et al, 1993;Bjorvatn and Ursin, 1994;Monti et al, 1995;Bjorvatn et al, 1997;Boutrel et al, 1999Boutrel et al, , 2002.…”

Effects of Fluoxetine on the Polysomnogram in Outpatients with Major Depression

“…In normal controls , fluoxetine increases REM latency, decreases REM sleep, reduces total sleep time and efficiency, and increases wakefulness and Stage 1 sleep. However, it is generally devoid of any effect on slow wave sleep (von Bardeleben et al 1989;Saletu et al 1991;Hendrickse et al 1994;Nicholson and Pascoe 1988). In depressed patients , fluoxetine appears to prolong REM latency, reduce REM sleep, reduce REM density, and increase Stage 1 sleep (Hendrickse et al 1994).…”