Mirtazapine, but not fluvoxamine, normalizes the blunted REM sleep response to clonidine in depressed patients: implications for subsensitivity of alpha₂-adrenergic receptors in depression

Abstract 

To determine whether α₂-adrenergic receptor (α₂AR) 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 α₂-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 α₂AR subsensitivity is a trait marker of depression and suggest that the effects of these two antidepressants on α₂AR sensitivity may not be linked to the alleviation of depression.

Keywords: Major depressive disorder, REM sleep, Alpha₂-adrenergic receptor, Selective serotonin reuptake inhibitor, Alpha₂-adrenergic receptor antagonist