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: Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.Drugs 02/2005; 65(7):927-47. · 4.13 Impact Factor
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ABSTRACT: In DSM-IV the occurrence of disturbed sleep is one of the principal diagnostic criteria for major depressive disorder (MDD). Further, there is evidence of reciprocity between the two conditions such that, even in the absence of current depressive symptoms, disturbed sleep often predicts their development. The present review discusses the effects of antidepressants on sleep and evaluates the use of the recently developed melatonin agonist–selective serotonin antagonists on sleep and depression. Although many antidepressants such as the tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, several serotonin receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) have all been found successful in treating depression, their use is often associated with a disruptive effect on sleep. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their instigation or exacerbation of insomnia. The recently introduced novel melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT1 and MT2 receptor agonist and 5-HT2c antagonist properties, has been useful in treating patients with MDD. Its rapid onset of action and effectiveness in improving the mood of depressed patients has been attributed to its ability to improve sleep quality. These properties underline the use of melatonin analogues as a promising alternative for the treatment of depression.The World Journal of Biological Psychiatry 12/2009; 10(4_2):342-354. · 3.57 Impact Factor
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ABSTRACT: Although sleepiness and fatigue are common symptoms in depressed patients, the relationships among sleepiness, fatigue and treatment of depression have not been fully elucidated. The main objective of this study was to investigate the therapeutic effects of a sedating antidepressant on sleepiness and fatigue in patients with depression. Forty-two depressed patients, who met DSM-IV diagnostic criteria, and 32 matched healthy controls participated in the baseline measurements. Sixteen of the depressed patients were treated with mirtazapine. At baseline, daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) and Stanford Sleepiness Scale (SSS), and fatigue was assessed using the Fatigue Severity Scale (FSS) and Fatigue Impact Scale (FIS). During treatment, Multiple Sleep Latency Test (MSLT), ESS and SSS were used to measure daytime sleepiness, and the FIS, FACES Checklist-Fatigue subscale (FAF) and Fatigue Assessment Instrument (FAI) were used to measure fatigue. At baseline, there were significant group differences between the depressed and healthy controls on the ESS (P = 0.001), SSS (P<0.001), FSS (P < 0.001) and FIS (P < 0.001). Significant improvement of sleepiness and fatigue measures was seen after treatment with mirtazapine on the MSLT (P = 0.011), ESS (P = 0.021), SSS (P = 0.001), FIS (P = 0.002) and FAF (P = 0.004). Open-label treatment and relatively small sample size. Daytime sleepiness and fatigue are significant symptoms in depressed patients. Slightly paradoxically, a sedating antidepressant may alleviate these symptoms.Journal of affective disorders 05/2011; 134(1-3):421-6. · 3.76 Impact Factor