Emergence of Ketamine as a Rapid Acting Antidepressant: Mechanistic Insights and Future Directions

Ketamine, originally developed as a dissociative anesthetic, has recently gained attention for its rapid antidepressant effects, particularly in treatment-resistant depression and suicidal ideation. Unlike traditional antidepressants that take weeks to work, ketamine can produce clinical effects within hours. Its mechanism involves modulation of glutamate via NMDA and AMPA receptors, as well as downregulation of BDNF. This chapter reviews the mechanisms behind ketamine's antidepressant activity, along with its pharmacokinetics, toxicology, and ongoing clinical trials.

Study at a glance

Abstract

Ketamine is a phencyclidine derivative and N-methyl-D-aspartate receptor antagonist, widely popular as a dissociative anesthetic. Its use as an anesthetic in humans was progressively fallen out due to its associated adverse effects and the emergence of newer and safer anesthetics. In recent few decades, various reports related to its efficacy in the treatment of resistant depression with anti-suicidal potential draw significant attention from researchers around the globe. The rapid clinical effect of ketamine within hours as compared to traditional antidepressants that take several weeks makes it a hot topic in antidepressant research. Studies conducted in the recent past suggest its mechanism of action through glutamate modulation via receptors like NMDA, AMPA as well as downregulation of BDNF etc. This chapter will shed light on the various mechanisms of ketamine related to antidepressant activity. Along with that its pharmacokinetics, toxicology and ongoing clinical trials will also be discussed.