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

About 20-25% of people with major depressive disorder do not respond to standard antidepressants, prompting the search for new treatments. Ketamine, which acts on the NMDA receptor, has drawn substantial research interest. Nitrous oxide, used for over a century as an anesthetic and analgesic, is now being studied for treatment-resistant depression. This review covers nitrous oxide's use as a psychiatric intervention, its current applications in psychiatry, proposed mechanisms of action, and future research directions, including knowledge gaps and other potential psychiatric uses.

Study at a glance

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.