Targeting inflammatory pathways for treatment of the major depressive disorder

Drug Discov Today. 2023 Sep;28(9):103697. doi: 10.1016/j.drudis.2023.103697. Epub 2023 Jul 6.

Abstract

Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse effects confine the use of these conventional antidepressants to a limited subset of MDD patients. The classical antidepressants are increasingly proving unsatisfactory in tackling the treatment-resistant depression (TRD). Hence, the focus of treatment is shifting to alternative pathogenic pathways involved in depression. Preclinical and clinical evidences accumulated across the last decades have unequivocally affirmed the causative role of immuno-inflammatory pathways in the progression of depression. There is an upsurge in the clinical evaluations of the drugs having anti-inflammatory effects as antidepressants. This review highlights the molecular mechanisms connecting the inflammatory pathways to the MDD and current clinical status of inflammation modulating drugs in the treatment of MDD.

Keywords: TNF-α; astrocytes; depression; inflammation; kinins.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / metabolism
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Humans
  • Inflammation / drug therapy

Substances

  • Antidepressive Agents