Vortioxetine-Associated Rapid Eye Movement (REM) Sleep Alterations: A Focused Narrative Review of Human Polysomnographic Evidence

This focused narrative review examines the relationship between vortioxetine and rapid eye movement (REM) sleep and considers the potential clinical significance of REM-related changes observed during treatment. Direct human polysomnographic evidence remains very limited and is derived principally from two studies. The review integrates relevant sleep neurobiology, vortioxetine pharmacology, and human polysomnographic findings while distinguishing biological plausibility from demonstrated clinical significance. The available evidence is interpreted cautiously because changes in individual REM measures do not necessarily represent a uniform alteration of REM physiology and an objective polysomnographic effect should not be assumed to reflect a therapeutic mechanism. At present, vortioxetine-associated REM changes are best regarded as a pharmacodynamic effect whose persistence, dose dependence, underlying mechanism, and clinical relevance remain uncertain. These changes have not been established as surrogate markers of antidepressant response or other meaningful patient outcomes. Further prospective research integrating objective sleep measures with symptoms, subjective sleep quality, daytime functioning, cognition, and longer-term outcomes is needed to clarify the significance of vortioxetine-associated REM alterations.