Esketamine: a glimmer of hope in treatment-resistant depression

Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):417-429. doi: 10.1007/s00406-019-01084-z. Epub 2019 Nov 19.

Abstract

The motive of this article is to review the pharmacological and clinical aspects of esketamine (ESK), an NMDA-receptor antagonist approved recently by the FDA for treatment-resistant depression (TRD). PubMed/Medline database was searched using keywords 'esketamine' and 'depression', 'S-ketamine' and 'depression', and 'NMDA antagonist' and 'depression'. Individual trials were searched from ClinicalTrials.gov. We included English-language articles evaluating pharmacokinetics and pharmacodynamics of intranasal (IN) esketamine, along with clinical trial data related to its efficacy and safety in patients diagnosed with TRD. Compared to placebo, IN esketamine causes significant and rapid improvement in depression. Dizziness, vertigo, headache, increase in blood pressure are some of its common adverse effects. With the growing number of patients of TRD, additional effective and safe treatment is the need of the hour. Esketamine appears to be an effective therapy when combined with oral antidepressants in patients with TRD. It is of special value due to the rapid onset of its action. Long-term clinical studies are, however, needed to ascertain its safety profile.

Keywords: Intranasal; NMDA; Rapid onset; Treatment-resistant depression.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / pharmacology*
  • Clinical Trials, Phase III as Topic*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Drug Therapy, Combination
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacokinetics
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Humans
  • Ketamine / adverse effects
  • Ketamine / pharmacokinetics
  • Ketamine / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Esketamine
  • Ketamine