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Key Words
Mirtazapine * Major depressive disorder * Sleep * alpha^sub 2^-Adrenoceptor
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.
Introduction
Mirtazapine, a novel antidepressant, is a member of a chemical series of compounds known as piperazinoaze-- pines. It has a different pharmacological profile compared with that of tricyclic and SSRI antidepressants, which is described by the acronym NaSSA (noradrenergic and specific serotonergic antidepressant). Mirtazapine probably acts by facilitation of noradrenergic and serotoninergic transmission via a new mechanism of action involving blockade of presynaptic az-adrenergic auto- and heteroreceptors [1, 2].
In the treatment of depression, mirtazapine is significantly more effective than placebo, has equivalent efficacy versus amitriptyline [3-5], clomipramine [6], and doxepin [7] and is significantly more effective than trazodone [8]. More recent studies have shown that mirtazapine is at least as effective as the SSRIs fluoxetine [9], citalopram [10] and paroxetine [11], but they also suggest that mirtazapine has a faster onset of action than these SSRIs [911]. The effective therapeutic daily dose of mirtazapine is between 15 and 45 mg, given as a single evening dose [12]. As far as sleep is concerned, mirtazapine consistently reduces subjective sleep disturbances in depressed patients, this effect being better than placebo and equivalent to that of amitriptyline [13].
Polygraphic sleep studies in rats have shown that mirtazapine modifies the sleep-waking pattern in rats in a dose-dependent manner. At 1 mg/kg intraperitoneally, mirtazapine reduces waking behavior, increases deep sleep, while having no effect on quiet sleep and rapid eye movement (REM) sleep. At 3.2 mg/kg intraperitoneally, mirtazapine...