The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression: a systematic review of clinical trials

Eur Arch Psychiatry Clin Neurosci. 2023 Feb;273(1):129-155. doi: 10.1007/s00406-022-01460-2. Epub 2022 Jul 13.

Abstract

Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n = 587), 2 with oral ayahuasca (1 mL/kg) and 10 with ketamine (mostly intravenous 0.5 mg/kg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamine's and classical hallucinogens' antidepressant effect. The PROSPERO ID for this study is CRD42021249089.

Keywords: BDNF; Biomarkers; Ketamine; Psychedelics; Treatment-resistant depression.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Biomarkers
  • Depression / drug therapy
  • Depressive Disorder, Treatment-Resistant* / therapy
  • Hallucinogens* / therapeutic use
  • Humans
  • Ketamine* / pharmacology

Substances

  • Ketamine
  • Hallucinogens
  • Antidepressive Agents
  • Biomarkers