Polysomnographic and symptomatological analyses of major depressive disorder patients treated with mirtazapine

Supportive Care in Cancer, 2008

Goals of the work This study aimed to compare the effectiveness of mirtazapine and imipramine on not only the distressing symptoms of cancer patients such as pain, nausea, vomiting, appetite loss, and sleep disturbances but also depressive and anxiety symptoms. Materials and methods Fifty-three patients with cancer who were diagnosed with major depressive disorder, anxiety disorder, or adjustment disorder were included. Twenty patients on mirtazapine, 13 patients on imipramine, and 20 patients in the control group without medication were interviewed during three visits (baseline, third week, and sixth week). Pain, nausea, vomiting, appetite loss, and sleep disturbances were evaluated with self-assessment single-symptom scales during each visit. The patients were also asked to complete the Hospital Anxiety Depression Scale (HADS) during each visit. Main results There were no significant differences among the three visits in the mirtazapine, imipramine, or control groups in terms of pain, nausea, vomiting, or appetite loss. For the initial, middle, and late insomnia, only the mirtazapine group showed improvements (p = 0.001, p = 0.001, p = 0.003). There were also significant differences in the mean total (p = 0.03), anxiety (p = 0.003), and depression (p = 0.025) scores of HADS among the three visits for patients taking mirtazapine. There were no significant differences for HADS scores from the baseline to the end point for patients taking imipramine or control group patients. Conclusion Our findings suggest that mirtazapine is effective for resolving insomnia as well as anxiety and depressive symptoms in cancer patients. However, more systematic research, such as placebo-controlled studies, is needed.

Journal of Clinical Psychopharmacology, 2016

The antidepressant mirtazapine is an alternative to classical hypnotics, and this study investigated the efficacy and safety of esmirtazapine (Org 50081, the maleic acid salt of S-mirtazapine) in patients given a diagnosis of primary insomnia after acute (2-day) treatment. Patients aged 18 to 65 years with primary insomnia were randomized to receive placebo or 1.5-, 3.0-, or 4.5-mg esmirtazapine in a balanced 4-way crossover study; 2 sleep laboratory nights with polysomnography were separated by 5-day, single-blind placebo washout periods. Polysomnographydetermined total sleep time (primary end point) and patient-reported total sleep time improved by at least 25 minutes with all 3 doses of esmirtazapine (P ≤ 0.001 vs placebo). Polysomnography-measured wake time after sleep onset (P ≤ 0.0001) and latency to persistent sleep also improved vs placebo (P ≤ 0.01, 3.0 and 4.5 mg). Patient-reported sleep quality improved with 3.0-and 4.5-mg esmirtazapine (P ≤ 0.01 and P ≤ 0.05, respectively, vs placebo). Morning alertness and contentment were not altered after esmirtazapine, and calmness increased with 4.5-mg esmirtazapine vs placebo. Evening questionnaires showed no difference in duration of daytime naps but reduced energy and ability to work/function after esmirtazapine treatment periods vs placebo (P < 0.05), although this effect was limited to the first night of each 2-night period. There were few adverse events, no serious adverse events, or clinically relevant treatment differences in vital signs, laboratory values, or electrocardiogram. Esmirtazapine doses of 1.5 to 4.5 mg/day significantly improved quantity and quality of sleep and were generally well tolerated, with no evidence of safety concerns or consistent pattern of residual effects.

Geriatrics Gerontology Aging

Prescription of approved hypnotics for insomnia decreased by more than 50%, whereas of antidepressive agents outstripped that of hypnotics. However, there is little data on their efficacy to treat insomnia, and many of these medications may be associated with known side effects. Antidepressants are associated with various effects on sleep patterns, depending on the intrinsic pharmacological properties of the active agent, such as degree of inhibition of serotonin or noradrenaline reuptake, effects on 5-HT1A and 5-HT2 receptors, action(s) at alpha-adrenoceptors, and/or histamine H1 sites. Mirtazapine is a noradrenergic and specific serotonergic antidepressive agent that acts by antagonizing alpha-2 adrenergic receptors and blocking 5-HT2 and 5-HT3 receptors. It has high affinity for histamine H1 receptors, low affinity for dopaminergic receptors, and lacks anticholinergic activity. In spite of these potential beneficial effects of mirtazapine on sleep, no placebo-controlled randomized clinical trials of mirtazapine in primary insomniacs have been conducted. Mirtazapine was associated with improvements in sleep on normal sleepers and depressed patients. The most common side effects of mirtazapine, i.e. dry mouth, drowsiness, increased appetite and increased body weight, were mostly mild and transient. Considering its use in elderly people, this paper provides a revision about studies regarding mirtazapine for sleep disorders.

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2013

Effects of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Åsberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and &lt; 4, respectively). In total, 1808...

Case Reports in Psychiatry

Introduction. Sleep disturbance and insomnia are some of the most frequent complaints in patients suffering from depression. Some common antidepressant with excitatory effects may worsen sleep qualities, whereas others (like mirtazapine), thanks to their antihistaminergic action, are associated with sedative properties and can quickly improve sleep quality. In the case of mirtazapine, even if its mechanisms of action on sleep remain controversial, beneficial changes in sleep pattern may be observable since the first dose and are associated with a faster onset of the antidepressive action. Case Presentation. Despite these documented beneficial effects, we reported five cases of elderly patients (age ranging from 69 to 79) with various diagnoses and comorbidities (severe or recurrent depression, general anxiety disorder, borderline personality disorder, and Parkinson’s disease) assessed during clinical daily routine for whom the use of mirtazapine was linked to the onset of nightmares...

Human Psychopharmacology: Clinical and Experimental, 2006

Objective To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety. Method An open-labelled, prospective, multicenter, non-comparative trial was conducted during a 2-year period in patients with major depression according to DSM-IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events. Results 192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall. Conclusion The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population.

Neuropsychiatric Disease and Treatment, 2005

The purpose of this open multicenter study of 4771 patients with a DSM-IV diagnosis of Major Depressive Episode was to analyse the response to mirtazapine in general practice and primary care. Patients with a baseline score of at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were treated with mirtazapine for 6 weeks (30 mg/day) and clinically assessed by their psychiatrists at weekly intervals through the MADRS and Clinical Global Improvement (CGI) rating scales. The data analysis was carried out on an "intent-to-treat" basis to collect outcome information on all patients. Our results suggested that the efficacy of the antidepressant effect relates to a nonspecific process. Nearly all patients (95%) showed at least slight improvement at the end of the observation period, while the response to treatment was independent of the clinical forms of depression. In particular, all measures of efficacy displayed the maximum change within the first 2 weeks of treatment, with further improvement occurring at much slower rates. Significant improvement within the first 2 weeks of treatment was highly predictive of the final response, and can serve as a guideline for clinicians when deciding about increased dosage, augmentation, or change of medication in unresponsive patients. Detailed analyses of individual MADRS items showed that mirtazapine's pharmacological profile, unlike selective serotonin reuptake inhibitors, led relatively quickly to a significant reduction of suicidal thoughts, a fact of particular clinical relevance.

Sleep Medicine, 2015

reported outcomes, total sleep time Role of the funding source: This study was funded by Organon, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ. Key individuals under the employment of Merck & Co., Inc. who were involved in the design and conduct of the study appear as authors on the manuscript, and were involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. HIGHLIGHTS  Esmirtazapine has a novel mechanism vs. other hypnotics (5-HT2A/H1 antagonist)  This 2-week outpatient study evaluated esmirtazapine vs. placebo in primary insomnia  Esmirtazapine significantly improved sleep onset, duration and quality vs. placebo  There was no evidence of rebound insomnia after discontinuation of esmirtazapine  Esmirtazapine was well tolerated; ≤7% of patients withdrew due to adverse events ABSTRACT Background: Esmirtazapine (Org 50081), a high-affinity antagonist at 5-HT 2A and H 1 receptors, was assessed for its hypnotic efficacy. Methods: In this double-blind, randomized study, non-elderly patients with primary insomnia (but otherwise healthy) were treated with esmirtazapine (1.5, 3.0, or 4.5 mg) or placebo for 2 weeks. The primary endpoint was patient-reported total sleep time (TST); other patient-reported endpoints included sleep latency (SL), wake time after sleep onset (WASO), number of awakenings, sleep quality, and satisfaction with sleep duration. Measures to assess the potential adverse effects of treatment included morning alertness, daytime function/napping, and rebound insomnia during a single-blind placebo run-out week after treatment ended. Adverse events (AEs) were also assessed. Results: Overall, 526 patients were randomized and 463 (88%) completed treatment. All esmirtazapine doses significantly improved TST, SL, sleep quality, and satisfaction with sleep duration versus placebo. Relative to placebo, TST was increased by 30-40 min and SL decreased by ~12 min for all doses. The highest dose (4.5 mg) also significantly reduced

1999

Sleep, 2008

Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials. Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10-40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15 mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA. Two patients ...

Depression and …, 2001

This review summarizes current findings regarding effects of antidepressant compounds on sleep architecture and interprets their clinical relevance. Effects of the major classes of antidepressant drugs on sleep properties are presented, with the antidepressant compounds organized into categories based primarily on their putative mechanism of action. The majority of antidepressant compounds, across several different categories, exhibit robust suppression of REM sleep. Others, such as bupropion and nefazodone, lack REM suppressant effects. Such findings support the idea that critical neurochemical mechanisms involved in the regulation of discrete sleep stages can be elucidated by means of polysomnographic investigations utilizing pharmacologically targeted agents. Clinicians have appreciated the importance of antidepressant drug effects on sleep when considering therapeutic options for patients. While such decisions in the past were based on empirical observations, an increasing amount of information regarding specific effects of different antidepressant drugs on sleep continuity and sleep architecture is available. Thus, clinicians may choose to consider profiles of sleep effects for different antidepressant drugs in the initial selection of an antidepressant compound. Depression and Anxiety 14:19-28, 2001.

Journal of Clinical Psychopharmacology, 2015

Journal of Affective Disorders, 2002

Current Psychiatry Reviews, 2012

Introduction: Depression is a common disorder associated with significant disability and is a substantial burden on the individual, their relatives and friends, and on society as a whole. Sleep disturbances are key features of depressive symptomatology, with more than 80% of depressed patients complaining of poor quality sleep.

The Primary Care Companion to The Journal of Clinical Psychiatry, 1999

Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is characterized by a unique receptorspecific pharmacologic profile and tolerable side-effect profile in comparison to other antidepressants. It has been reported to have a low incidence of agitation, anxiety, and insomnia, which may be due to blockade of 5-HT 2 and 5-HT 3 receptors. This unique multireceptor-mediated clinical pharmacologic profile may reduce the need for polypharmacy in selected patients.