Frontiers in Psychiatry (Dec 2015)

Treatment-Resistant Major Depression:Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

  • Charles eZorumski,
  • Peter eNagele,
  • Stephen James Mennerick,
  • Charles eConway

DOI
https://doi.org/10.3389/fpsyt.2015.00172
Journal volume & issue
Vol. 6

Abstract

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Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15-30% of MDD patients. There has been recent interest in N-methyl-D-aspartate (receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant.

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