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: Circadian rhythm abnormalities, as shown by sleep/wake cycle disturbances, constitute one the most prevalent signs of depressive illness, advances or delays in the circadian phase, or changes in rhythmsámplitude, being documented in patients with major depressive disorder (MDD), seasonal affective disorder or bipolar disorder. The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders, thus suggesting that a link between chronobiological disturbances and depressed mood exists. Studies testing variants of genes that control the circadian system have reported circadian gene polymorphisms in depressive illness. 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 the sleep/wake cycle. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their exacerbation of insomnia. The recently introduced melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT 1 and MT 2 receptor agonist and 5-HT 2c 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/wake cycle quality. Thus, current conceptualization of depressive illness needs to be expanded to include the role of circadian dysregulation in the development of the disease.