Citation

Zorumski CF, Nagele P, Mennerick S, Conway CR. Front. Psychiatry 2015; 6: 172.

Affiliation

Department of Psychiatry, Washington University School of Medicine , St. Louis, MO , USA ; Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine , St. Louis, MO , USA.

Copyright

(Copyright © 2015, Frontiers Media)

DOI

10.3389/fpsyt.2015.00172

PMID

26696909

PMCID

PMC4673867

Abstract

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.

Language: en