Glutamatergic modulators: the future of treating mood disorders?

Harv Rev Psychiatry. Sep-Oct 2010;18(5):293-303. doi: 10.3109/10673229.2010.511059.


Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and recurrent conditions affecting millions of individuals worldwide. Existing antidepressants and mood stabilizers used to treat these disorders are insufficient for many. Patients continue to have low remission rates, delayed onset of action, residual subsyndromal symptoms, and relapses. New therapeutic agents able to exert faster and sustained antidepressant or mood-stabilizing effects are urgently needed to treat these disorders. In this context, the glutamatergic system has been implicated in the pathophysiology of mood disorders in unique clinical and neurobiological ways. In addition to evidence confirming the role of the glutamatergic modulators riluzole and ketamine as proof-of-concept agents in this system, trials with diverse glutamatergic modulators are under way. Overall, this system holds considerable promise for developing the next generation of novel therapeutics for the treatment of bipolar disorder and major depressive disorder.

Publication types

  • Review

MeSH terms

  • Bipolar Disorder / drug therapy
  • Depressive Disorder, Major / drug therapy
  • Excitatory Amino Acid Agents / therapeutic use*
  • Humans
  • Ketamine / therapeutic use
  • Mood Disorders / drug therapy*
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / physiology
  • Riluzole / therapeutic use


  • Excitatory Amino Acid Agents
  • Receptors, Glutamate
  • Ketamine
  • Riluzole