Effects of Mirtazapine on Sleep Polygraphic Variables in Major Depression

Abstract

Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively.

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

“…This methodological issue may contribute to differences between nights À1 and 2. Two studies reported an increase of REM latency: one in healthy subjects (Ruigt et al, 1990) and the other in depressed patients (Schittecatte et al, 2002a). This finding could not be replicated in all other reports (Winokur et al, 2000(Winokur et al, , 2003Aslan et al, 2002), including the present study.…”

“…When compared to baseline, sleep latency decreased and total sleep time and sleep efficiency increased during week 1 with similar results in week 2 (Winokur et al, 2000). In a larger sample, Schittecatte et al (2002a) found more distinct sleep-improving effects of mirtazapine. Already after 2 days administration of 15 mg, total sleep time, sleep efficiency index, and time spent in stage 2, REM, and SWS increased, whereas sleep latency and stage awake decreased.…”

“…Also in our study, nine of 10 patients reported suffering from disturbed sleep before treatment. Information about this issue is not provided by Schittecatte et al (2002a). We found, however, an increase of SWS at day 28.…”

“…Moreover, in healthy controls, acute mirtazapine administration (30 mg) increased SWS (Ruigt et al, 1990;Aslan et al, 2002). Similarly, Schittecatte et al (2002a) reported an increase of SWS after a 2-day treatment of depressed patients with mirtazapine. In accordance with Winokur et al (2000), we did not observe a change of SWS shortly after the beginning of mirtazapine treatment.…”

“…Sleep-EEG studies in rats showed that a lower dose of mirtazapine prompted increases of slow-wave sleep (SWS) and decreases of wakefulness, whereas a higher dose prompted suppression of rapid-eye-movement (REM) sleep and increases of SWS (Schittecatte et al, 2002a). In young normal male subjects after 30 mg of the substance given before bedtime sleep, stages awake and 1 decreased and one component of SWS, stage 3, increased (Ruigt et al, 1990).…”