title: Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy.
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.
authors.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.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Zorumski
authors.affiliation: Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine , St. Louis, MO , USA ; Department of Anesthesiology, Washington University School of Medicine , St. Louis, MO , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Nagele
authors.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.
authors.forename: Steven
authors.initials: S
authors.lastname: Mennerick
authors.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.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Conway
keywords: NMDA receptors; antidepressant; hippocampus; ketamine; metaplasticity; suicide