The effects of mirtazapine on sleep: a placebo controlled, double-blind study in young healthy volunteers.
ABSTRACT Mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant. This study aims at objectively investigating the effects of single-dose mirtazapine on sleep of healthy volunteers.
We studied the effect of acute administration of mirtazapine (30 mg) on the sleep polysomnogram, using a double-blind, placebo-controlled design. Subjects spent 3 consecutive nights in the laboratory. First night allowed for adaptation to the laboratory and application of electroencephalogram electrodes, while the second and third nights were reserved for recording baseline sleep and studying the effects of drug treatment, respectively.
Young healthy volunteers (n=20), with a mean age of 24 years, were randomly separated into two groups: placebo (n=10) and mirtazapine (n=10).
On the third night, subjects received either placebo or mirtazapine. Comparisons were made between sleep variables from baseline values in both groups. Independent samples t-test was utilized to evaluate the differences between the two groups.
Mirtazapine improved the variables related to sleep continuity when compared with placebo. It increased the sleep efficiency index, while decreasing the number of awakenings and their duration. The slow wave sleep time was increased, while the stage 1 sleep time was decreased significantly. There was no significant effect on rapid eye movement sleep variables.
Our findings suggest that mirtazapine has considerable effects on slow wave sleep. Further studies are recommended to investigate the efficiency of antidepressants, in respect to the effects of 5-HT2 blockade on slow wave sleep.
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ABSTRACT: Study Objectives: Recent evidence suggests that certain antidepressants are associated with an increase of periodic leg movements (PLMS) that may disturb sleep. So far, this has been shown in patients clinically treated for depression and in cross-sectional studies for various substances, but not mirtazapine. It is unclear whether antidepressants induce the new onset of PLMS or only increase preexisting PLMS, and whether this is a general property of the antidepressant or only seen in depressed patients. We report here the effect of mirtazapine on PLMS in young healthy men. Design: Open-labeled clinical trial (NCT00878540) including a 3-week preparatory phase with standardized food, physical activity, and sleep-wake behavior, and a 10-day experimental inpatient phase with an adaptation day, 2 baseline days, and 7 days with mirtazapine. Setting: Research institute. Participants: Twelve healthy young (20-25 years) men. Interventions: Seven days of nightly intake (22:00) of 30 mg mirtazapine. Measurements and results: Sleep was recorded on 2 drug-free baseline nights, the first 2 drug nights, and the last 2 drug nights. Eight of the 12 subjects showed increased PLMS after the first dose of mirtazapine. Frequency of PLMS was highest on the first drug night and attenuated over the course of the next 6 days. Three subjects reported transient restless legs symptoms. Conclusions: Mirtazapine provoked PLMS in 67% of young healthy males. The effect was most pronounced in the first days. The possible role of serotonergic, noradrenergic and histaminergic mechanisms in mirtazapine-induced PLMS is discussed.Sleep 05/2013; 36(05):661-669. · 5.10 Impact Factor
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ABSTRACT: BACKGROUND:Data from an open-label trial suggest that mirtazapine might prove useful in treatment of fibromyalgia syndrome (FMS).OBJECTIVE:To obtain preliminary efficacy data of mirtazapine for estimation of sample size requirements for a Phase 2 clinical trial in FMS.METHODS:This 13-week randomized controlled trial compared the effects of mirtazapine 15 mg/day, mirtazapine 30 mg/day, and placebo in 40 patients with FMS. The primary outcomes were change in Pain Visual Analog Scale (PVAS) and proportion of pain responders (≥30% PVAS reduction). Secondary outcomes included scores from the Jenkins Sleep Scale (JSS), Patient Global Impression of Change (PGIC), Fibromyalgia Impact Questionnaire (FIQ), Hamilton Depression Rating Scale (HAM-D), Patient Global Assessment, and self-reported adverse events.RESULTS:Significant within-group PVAS reductions from baseline were observed in all 3 groups, with the greatest improvement in the mirtazapine 30-mg group (p < 0.005); between-group difference was not significant. The proportion of pain responders did not meet significance criteria (66.67% for mirtazapine 30 mg, 50% for mirtazapine 15 mg, 41.67% for placebo). Significant within-group improvement in JSS scores was seen for mirtazapine 30 mg (p < 0.01) and mirtazapine 15 mg (p < 0.05). Between-group comparison achieved significance for JSS item 3, waking several times per night (p < 0.05). On the PGIC, 72.73% felt better with both mirtazapine dosages compared with 50% for placebo. Within-group FIQ responses indicated improvement in only mirtazapine-treated groups, whereas within-group improvement for HAM-D and Patient Global Assessment was observed in all groups. Based on our findings, the sample size requirement (80% power, 5% type I error) should be 83 per group to detect PVAS change difference between mirtazapine 30 mg and placebo. Common mirtazapine-related adverse events were increased appetite and weight gain.CONCLUSIONS:Patients with FMS taking mirtazapine exhibited within-group significant improvement in most of the measured outcomes. Between-group analysis was predictably compromised by the small sample size. Mirtazapine was well tolerated. Further study with a larger sample size is likely to be useful.Annals of Pharmacotherapy 06/2013; · 2.57 Impact Factor
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ABSTRACT: There is an interdependent relationship between insomnia and fatigue in the medical literature, but both remain distinct entities. Insomnia entails problematic sleep initiation, maintenance, or restoration with an accompanying decrease in perceived daytime function. Lethargy is a symptom that has a wide differential diagnosis that heavily overlaps with cancer-related fatigue; however, insomnia may contribute to worsened fatigue and lethargy in cancer patients. Insomnia is a major risk factor for mood disturbances such as depression, which may also contribute to lethargy in this at-risk population. The pathophysiology of fatigue and insomnia is discussed in this review, including their differential diagnoses as well as the emerging understanding of the roles of neurotransmitters, branched-chain amino acids, and inflammatory cytokines. Treatment approaches for insomnia and fatigue are also discussed and reviewed, including the role of hypnotics, psychotropics, hormonal agents, and alternative therapies.Current Oncology Reports 04/2014; 16(4):377. · 3.33 Impact Factor