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New targets for rapid antidepressant action.

Rodrigo Machado-Vieira1, Ioline D Henter2, Carlos A Zarate1

  • 1Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

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|January 3, 2016
PubMed
Summary

Novel glutamate receptor modulators offer faster relief for major depressive disorder (MDD) and bipolar disorder (BD) than traditional treatments. Research explores N-methyl-d-aspartate (NMDA) antagonists and other glutamate pathways for rapid antidepressant effects.

Keywords:
AntidepressantBipolar disorderDepressionGlutamateRapidTreatment

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Area of Science:

  • Neuroscience and Pharmacology
  • Psychiatry and Mental Health

Background:

  • Current treatments for major depressive disorder (MDD) and bipolar disorder (BD) have slow onset and limited efficacy.
  • Monoaminergic mechanisms are the primary target of existing antidepressants.
  • Glutamate pathways are implicated in the pathophysiology of MDD and BD.

Purpose of the Study:

  • To review clinical evidence for novel glutamate receptor modulators as rapid-acting antidepressants.
  • To discuss various classes of glutamate receptor modulators, including NMDA receptor antagonists and metabotropic glutamate receptor modulators.

Main Methods:

  • Review of clinical evidence for glutamate receptor modulators.
  • Categorization of modulators by mechanism: non-competitive NMDA antagonists, GluN2B-specific NMDA antagonists, NMDA glycine-site partial agonists, and mGluR modulators.
  • Brief discussion of preclinical targets like AMPA agonists and mGluR2/3 negative allosteric modulators.

Main Results:

  • Ketamine, an N-methyl-d-aspartate (NMDA) antagonist, shows rapid and robust antidepressant effects.
  • Other NMDA receptor antagonists and novel glutamate modulators demonstrate varying degrees of antidepressant efficacy.
  • Non-glutamatergic targets like cholinergic and opioid systems are also being investigated for rapid antidepressant effects.

Conclusions:

  • Novel glutamate receptor modulators represent a promising therapeutic avenue for rapid antidepressant effects in MDD and BD.
  • Further research into these and other non-glutamatergic targets is warranted to address limitations of current treatments.