Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders

Nat Rev Drug Discov. 2008 May;7(5):426-37. doi: 10.1038/nrd2462.


Mood disorders are common, chronic, recurrent mental illnesses that affect the lives of millions of individuals worldwide. To date, the monoaminergic systems (serotonergic, noradrenergic and dopaminergic) in the brain have received the greatest attention in neurobiological studies of mood disorders, and most therapeutics target these systems. However, there is growing evidence that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in mood-disorder pathophysiology as well as the efficacy of glutamatergic agents in mood disorders. We also discuss exciting new prospects for the development of improved therapeutics for these devastating disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Glutamates / physiology*
  • Humans
  • Mood Disorders / drug therapy*
  • Mood Disorders / psychology
  • Psychotropic Drugs / therapeutic use*


  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Psychotropic Drugs