Mechanisms of the Rapid Effects of Ketamine on Depression and Sleep Disturbances: A Narrative Review

Recently, sleep has been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythm, which controls whole-body homeostasis and homeodynamics. Sleep disturbances can contribute to several physical and psychological disorders, including cardiovascular disease, obesity, depression, and cognitive dysfunction. The clinical use of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine began in the 1970s. Over the years, physicians have used it as a short-acting anesthetic, analgesic, and antidepressant; however, in-depth research has revealed new possible applications for ketamine, such as for treating sleep disturbances and circadian rhythm disorders. The aim of this narrative review is to examine the literature on the mechanistic role of the antidepressant ketamine in affecting sleep disturbance. Additionally, we discuss the pharmacologic and pharmacokinetic mechanisms of ketamine as an antidepressant and the predictive biomarkers for ketamine’s effect on sleep and cognitive function.