Vortioxetine transiently alters basal locomotor activity but does not produce sedation in rats

Sedation is a major side effect of many pharmacotherapies for depression, negatively affecting treatment compliance, particularly in long-term treatment. Vortioxetine, a recently approved antidepressant for major depressive disorder, has been reported in clinical studies to be safe and well-tolerated, without causing sedation. However, recent reports have indicated that vortioxetine may, in fact, cause daytime sedation. Therefore, this study aimed to explore the effects of acute and chronic administration of varying doses of vortioxetine on sedation in rats. Sedation was assessed behaviorally using the rota-rod, spontaneous locomotor activity, and fixed-bar tests. In addition to behavioral assessments, the sedation rating scale was used, and body weight was monitored to indicate metabolic effects of different vortioxetine doses (5, 10, and 20 mg/kg). Our results showed that, compared to trazodone, acute and chronic dosing of vortioxetine produced a transient reduction in spontaneous locomotor activity. Furthermore, the fixed-bar, rota-rod, and sedation ratings were not significantly altered by any dose of vortioxetine. These results suggest that vortioxetine, at the tested doses, is safe, well-tolerated, and does not produce significant sedative effects.