Elsevier

Biological Psychiatry

Volume 48, Issue 1, 1 July 2000, Pages 75-78
Biological Psychiatry

Brief report
Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study

https://doi.org/10.1016/S0006-3223(00)00882-9Get rights and content

Abstract

Background: Mirtazapine, a clinically effective antidepressant, acts by antagonizing central α2-adrenergic and 5-HT2/5-HT3 receptors. No data are available regarding mirtazapine’s effects on sleep architecture in patients with major depressive disorder.

Methods: Six patients meeting criteria for major depressive disorder and scoring ≥4 on the three Hamilton Depression Rating Scale sleep items were studied. Polysomnographic evaluations were performed at baseline and after 1 (15 mg at bedtime) and 2 weeks (30 mg at bedtime) of open-label mirtazapine treatment.

Results: Mirtazapine significantly decreased sleep latency and significantly increased total sleep time and sleep efficiency from baseline levels during week 1, with similar results observed after week 2. Mirtazapine did not significantly alter rapid eye movement sleep parameters. Clinically, Hamilton Depression Rating Scale and sleep disturbance ratings improved after treatment.

Conclusions: Mirtazapine significantly improves sleep continuity in major depressive disorder patients with poor sleep quality at weeks 1 and 2 of treatment, while preserving sleep architecture.

Introduction

The majority of major depressive disorder (MDD) patients subjectively report prolonged sleep onset and/or disturbed sleep continuity as the most prevalent symptoms (Winokur and Reynolds 1994). Objective polysomnographic (PSG) analysis of depressed patients reveals disrupted sleep continuity, altered rapid eye movement (REM) sleep timing, and reductions in slow-wave sleep (SWS) quantity (Kupfer and Reynolds 1992). Additionally, antidepressant drug administration elicits pronounced differences in PSG measures of sleep continuity and sleep architecture (Winokur and Reynolds 1994). Sedating antidepressants shorten sleep latency and improve sleep continuity, whereas more activating antidepressants prolong sleep latency and impair sleep continuity measures. Sleep architecture also may be differentially altered by antidepressant drugs (e.g., whereas many antidepressants potently suppress REM sleep, a few do not, despite similar efficacies in treating depression).

Effects of antidepressant drugs on sleep parameters are clinically relevant due to the frequency of sleep complaints in depressed patients. Although controlled studies have not evaluated sleep disorder symptoms as criteria in antidepressant drug selection for specific patients to enhance treatment outcome, clinical experience suggests this may represent an important basis for treatment selection.

The novel α2-adrenergic and 5-HT2/5-HT3 receptor antagonist, mirtazapine, is a clinically effective antidepressant drug Claghorn et al 1987, Pinder 1997. Subjective complaints of sleep disturbances improved significantly and rapidly in placebo-controlled studies of depressed patients treated with mirtazapine. Conversely, over half of patients receiving mirtazapine treatment reported daytime somnolence, as compared with 18% in patients randomized to a placebo (Organon 1996). These observations suggest that laboratory studies of mirtazapine’s effects on sleep physiology are important in guiding optimal use of this compound; yet, to date, only a single PSG study has examined mirtazapine. Ruigt et al (1990) administered mirtazapine (30 mg) or a placebo at 9:00 pm to six healthy subjects and observed decreased sleep latency, increased total sleep time, and reduced stage 1 sleep and increased stage 3 sleep, indicative of deeper sleep in treated subjects.

In this open-label study we examine the acute effects of 1- and 2-week mirtazapine administration on sleep continuity and sleep architecture variables by employing PSG techniques and subjective sleep measures in six patients with MDD accompanied by subjective sleep complaints.

Section snippets

Methods and materials

Subjects were recruited from the Psychiatry Department at Dartmouth Hitchcock Medical Center and from respondents to newspaper advertisements. Six patients provided informed consent, enrolled, and successfully completed the study. Patients were required to meet the following criteria: 18–65 years of age with a DSM-IV diagnosis of MDD based upon a semistructured interview; a score of ≥18 on the 17-item Hamilton Depression Rating Scale (HDRS), and a score of ≥4 on the three HDRS sleep items

Results

The PSG data demonstrated rapid improvement in sleep continuity measures, with significant changes from baseline observed after both treatment weeks in sleep latency [F(2,17) = 4.79, p = .009], total sleep time [F(2,17) = 16.3, p = .004], and sleep efficiency [F(2,17) = 10.1, p = .0003; Figure 1]. Objective improvements in sleep continuity were accompanied by improvements in HDRS and sleep disturbance scores (Table 1). Three of six subjects reported mild daytime sedation and one rated the

Discussion

Our results suggest that acute mirtazapine administration rapidly improves both subjective ratings of depression and objective physiologic parameters of sleep disturbance in patients with MDD accompanied by disturbed sleep. Although four of six subjects reported daytime somnolence during week 1 (15 mg), these complaints resolved by the end of week 2 (30 mg). Thus, patients may develop tolerance to mirtazapine’s sedating effects within a few days of treatment initiation. Conversely, no loss of

Acknowledgements

Funding provided by an unrestricted educational grant from Organon Inc. (AW).

References (13)

  • A.J. Rush et al.

    Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder

    Biol Psychiatry

    (1998)
  • J.L. Claghorn et al.

    The effectiveness of Org 3770 in depressed patients

    Psychopharmacol Bull

    (1987)
  • T. de Boer

    The pharmacologic profile of mirtazapine

    J Clin Psychiatry

    (1996)
  • W. Guy

    ECDEU Assessment Manual for Psychopharmacology

    (1976)
  • M. Hamilton

    A rating scale for depression

    J Neurol Neurosurg Psychiatry

    (1960)
  • C. Idzikowski et al.

    Human SWS is increased dose-dependently by seganserine and ritanserine

    Sleep Res

    (1989)
There are more references available in the full text version of this article.

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