Journal of the Neurological Sciences

Nitrous Oxide: an emerging novel treatment for treatment-resistant depression

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Conway, C. R., de Leon, V. C., Quach, D. F.

This review (2021) explores the possibilities of using Nitrous Oxide (NO2) for treating treatment-resistant depression (TRD). The use of NO2 as a psychiatric intervention is discussed along with its possible mechanism of action. Its antidepressant effects are believed to be mediated through the NMDA receptor.

Abstract

Stemming from the results of the historic STAR-D trial, it is evident that a significant subset of individuals (20-25%) with major depressive disorder (MDD) do not respond to conventional antidepressant medications. As a result, an emphasis has been placed on the development of novel therapeutics for MDD over the last two decades. Recently, substantial research efforts have been focused on the use of ketamine as an antidepressant whose mechanism of action is via the N-methyl-d-aspartate (NMDA) receptor. Another potential therapeutic compound of interest is nitrous oxide, which has been utilized for more than a century in multiple fields of medicine for its analgesic and anesthetic properties. Recent clinical studies suggest that nitrous oxide may be effective for treatment-resistant depression. In this review, we will discuss the administration of nitrous oxide as a psychiatric intervention, current use in psychiatry, putative mechanisms of action, and future directions highlighting knowledge gaps and other potential utilities in the field of psychiatry.