Abstract:
This article examines the pharmacodynamic mechanisms of classical
antidepressants and contrasts them with the emerging generation of rapid-acting agents,
particularly ketamine and esketamine. Traditional antidepressants, including SSRIs, SNRIs,
TCAs, and MAO inhibitors, primarily target monoaminergic neurotransmission and require
several weeks before clinical benefits appear. Their limitations, combined with high rates of
treatment resistance, have driven interest in novel approaches. Ketamine and esketamine
represent a major shift in antidepressant development due to their rapid onset of action and
unique effects on glutamatergic signaling, synaptic plasticity, and neurotrophic pathways. This
article explores the cellular and molecular principles underlying their therapeutic properties,
reviews clinical evidence, considers safety concerns, and outlines future research directions in
neurobiologically informed treatments for major depressive disorder.
