Major depressive disorder carries a significant burden and a high risk for suicide. The need for more effective, safer, and faster-acting drugs is, therefore, compelling. The present chapter briefly assesses the most promising agents, focusing on non-monoamine-targeting compounds, namely, the glutamate antagonist ketamine and its enantiomer esketamine. A critical overview of the evidence and the pitfalls associated with current antidepressant drug development is likewise provided in the following text.
Keywords: Esketamine; Ketamine; Major depressive disorder; Novel antidepressant; Treatment resistance.