Ketamine: Mechanisms and Relevance to Treatment of Depression

Annu Rev Med. 2024 Jan 29:75:129-143. doi: 10.1146/annurev-med-051322-120608. Epub 2023 Sep 20.


Major depressive disorder (MDD) is a leading cause of suicide in the world. Monoamine-based antidepressant drugs are a primary line of treatment for this mental disorder, although the delayed response and incomplete efficacy in some patients highlight the need for improved therapeutic approaches. Over the past two decades, ketamine has shown rapid onset with sustained (up to several days) antidepressant effects in patients whose MDD has not responded to conventional antidepressant drugs. Recent preclinical studies have started to elucidate the underlying mechanisms of ketamine's antidepressant properties. Herein, we describe and compare recent clinical and preclinical findings to provide a broad perspective of the relevant mechanisms for the antidepressant action of ketamine.

Keywords: NMDA receptor; antidepressant; hippocampus; ketamine; major depressive disorder; synaptic plasticity; treatment-resistant depression.

Publication types

  • Review

MeSH terms

  • Amines / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Depressive Disorder, Major* / drug therapy
  • Humans
  • Ketamine* / therapeutic use


  • Ketamine
  • Antidepressive Agents
  • Amines