ABSTRACT
To determine whether alpha(2)-adrenergic receptor (alpha2AR) subsensitivity is a state or a trait marker of depression, we consecutively challenged 32 drug-free depressed patients with a clonidine REM suppression test (CREST). We then treated the patients with fluvoxamine, a selective serotonin reuptake inhibitor, or mirtazapine, a selective alpha(2)-adrenergic receptor antagonist. The first 10 patients from each treatment group who recovered were given a second challenge test. The CREST values of the two treatment groups at each time point were compared, and also compared with the CREST values of a group of 10 normal subjects. Before treatment, the REM sleep response to clonidine in the two groups of patients was significantly blunted compared with the REM sleep response in the healthy subjects. After treatment, there was still an abnormal REM sleep response to clonidine in the fluvoxamine-treated patients, despite clinical recovery, but there was a normalized REM sleep response in the mirtazapine-treated patients. These results are compatible with the hypothesis that alpha2AR subsensitivity is a trait marker of depression and suggest that the effects of these two antidepressants on alpha2AR sensitivity may not be linked to the alleviation of depression.
Subject(s)
Adrenergic alpha-Agonists/adverse effects , Antidepressive Agents, Tricyclic/therapeutic use , Clonidine/adverse effects , Clonidine/therapeutic use , Depressive Disorder, Major/drug therapy , Fluvoxamine/pharmacology , Fluvoxamine/therapeutic use , Mianserin/analogs & derivatives , Mianserin/pharmacology , Mianserin/therapeutic use , Receptors, Adrenergic, alpha-2/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sleep, REM/drug effects , Female , Humans , MirtazapineABSTRACT
Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively.