5‐HT2 receptor antagonism and slow‐wave sleep in major depression

Abstract

Specific sleep disturbances such as reduced slow-wave sleep (SWS) and decreased serotonergic (5-HT) activity have been observed in depressive disorders. Ritanserin, a specific 5-HT2 receptor antagonist, has been shown to increase SWS in healthy subjects. This study explored the effects of a single dose or ritanserin (5 mg) on sleep electroencephalography in 18 major depressed patients and in 10 control subjects. Ritanserin affected SWS differently in the two groups. Although stage 3 increased significantly in the groups, in contrast to controls, there was no significant effect of ritanserin on stage 4 in depressed patients. In the depressed group, irritability and DSM-III-R melancholic type predicted 40% or the variance of stage 4 increment after ritanserin, as assessed by stepwise multiple regression. These results are in agreement with a potential 5-HT disturbance, particularly at the 5-HT2 receptor level, in some clinical forms of depression.

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging

“…Serotonin neuroendocrine studies in depressive illness have shown a blunted prolactin response to the 5-HT-releasing agent d-fenfluramine, which is mediated by the 5-HT 2A receptor (Cowen 1993). Differences in slow-wave sleep pattern response to the 5-HT 2A antagonist ritanserin between depressed patients and controls have also been reported (Staner et al 1992). Post mortem studies demonstrated increased 5-HT 2A receptors in the prefrontal cortex of suicide victims and depressed persons who died of natural causes (Arango et al 1990; Arora and Meltzer 1989b;Hrdina et al 1993;Stanley and Mann 1983), consistent with the hypothesis that 5-HT 2A receptors up-regulate in response to a defect in serotonergic neurotransmission.…”

“…Dysregulation of 5-HT function is believed to be involved in depression, impulsivity, and suicide (Arango et al 1992;Kennett 1991;Meltzer 1990;Staner et al 1992). Additionally, modulation of cholinergic neuronal activity by 5-HT may play a role in higher cognitive processes such as memory and 412 C.C.…”

Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model

“…The direct 5-HT 2C receptor blockade by a potent antagonist such as SB-206 553 has been shown to potentiate the antidepressant-like effects of imipramine in mice subjected to the forced swimming test (Yamada and Sugimoto, 2001). Although, up to date, a selective 5-HT 2C antagonist has not been demonstrated to be an effective antidepressant in large, double-blind, placebo-controlled clinical trials, there are clinical data to indicate that non-specific antagonists of 5-HT 2C receptors are effective in the treatment of depression (Strauss and Klieser, 1991;Staner et al, 1992) and alterations in 5-HT 2C receptor function and/or expression have been reported to occur in rats submitted to the learned helplessness test (Iwamoto et al, 2005) and in depressed patients who committed suicide, notably complex alterations in 5-HT 2C pre-mRNA editing sites preferences that suggests an overall decreased 5-HT 2C receptor activity in the prefrontal cortex of suicide victims with a history of major depression (Niswender et al, 2001;Gurevich et al, 2002;Iwamoto and Kato, 2003;Schmauss, 2003;Iwamoto et al, 2005).…”

New Onset Somnambulism Associated With Different Dosage of Mirtazapine

“…7 The mechanism of mirtazapine to improve sleep quality may depend on its selective 5-HT 2A/C antagonism more than on its H 1 antagonism. 8 It also found in other antidepressants such as ritanserin, nefazodone, and trazodone, which prolongs the duration of SWS. 8 It is an intriguing issue why only a higher dosage of mirtazapine (45 mg/d) induced sleepwalking in this depressed patient.…”