Ketamine and esketamine for crisis management in patients with depression: Why, whom, and how?

Eur Neuropsychopharmacol. 2022 Apr:57:88-104. doi: 10.1016/j.euroneuro.2022.02.004. Epub 2022 Feb 23.


Currently, only a limited number of interventions can rapidly relieve depressive symptomatology in patients with major depressive disorder or bipolar disorder experiencing extreme distress. Such crises, especially when suicide attempt or ideation is involved, are a major risk factor of suicide. Ketamine, a N-methyl-d-aspartate glutamate receptor antagonist, and its enantiomer esketamine rapidly reduce depressive symptoms in depressed patients with current suicidal ideation. Recently, esketamine has been approved for use in patients with depression at risk of suicide and for psychiatric emergency by major medical agencies in the United States and Europe, whereas ketamine is increasingly used off-label. However, there is currently limited guidance on why, when, and how to use these drugs in patients with depression to treat a crisis. In this review article, we provide a succinct overview of the cellular and molecular mechanisms of action of ketamine and esketamine, and of the functional brain changes following their administration. We also summarize the major clinical studies on ketamine and esketamine efficacy in patients experiencing a crisis (generally, suicidal ideation), and propose a profile of patients who can benefit most from such drugs, on the basis of neurobiological and clinical observations. Finally, we describe the administration mode, the efficacy and tolerability profiles, the side effect management, possible concomitant treatments and the issue of deprescribing.

Keywords: Crisis; Depression; Intervention; Ketamine; Suicide.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / adverse effects
  • Depression / drug therapy
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / psychology
  • Humans
  • Ketamine* / adverse effects
  • Suicidal Ideation


  • Antidepressive Agents
  • Esketamine
  • Ketamine