Comparative Sleep Architecture Profiles of Antidepressants in Mice: Pharmacological Characterization of Paroxetine, Sertraline, Duloxetine, Mirtazapine and Vortioxetine.

Sleep is a biological process essential for various brain functions, and patients with major depressive disorder (MDD) frequently experience sleep disturbances. Since such disturbances are both symptoms and risk factors for depression, evaluating the effects of antidepressants on sleep is important for understanding their clinical effectiveness. In this study, we investigated the effects of five antidepressants-paroxetine and sertraline (selective serotonin reuptake inhibitors), duloxetine (a serotonin-norepinephrine reuptake inhibitor), mirtazapine (a noradrenergic and specific serotonergic antidepressant), and vortioxetine (a serotonin reuptake inhibitor and modulator)-on sleep architecture in male mice using cortical electroencephalogram and electromyogram. Paroxetine and sertraline reduced rapid eye movement (REM) sleep, while duloxetine decreased REM sleep and increased non-REM (NREM) sleep. Mirtazapine reduced Wake and increased NREM sleep significantly, while vortioxetine also increased NREM sleep. Interestingly, among the five antidepressants tested, only paroxetine reduced Wake and increased NREM sleep during the dark period when administered prior to the light period. This is the first study to compare the effects of these five compounds on sleep architecture in mice within a single experimental framework. These findings were consistent with clinical observations, suggesting translational relevance. By reporting and comparing the sleep-related pharmacological profiles of these antidepressants, our findings may help guide the selection of appropriate treatments for patients with MDD, particularly those suffering from sleep disturbances.