Nitrous Oxide Shows Rapid Antidepressant Effects in Proof-of-Concept Trial
the MPR take:
Nitrous oxide is commonly used as an inhalational general anesthetic, but it may also have a therapeutic use for treatment-resistant major depression. Nitrous oxide modulates several CNS targets, with the primary target appearing to be the NMDA receptor; here, nitrous oxide acts as a non-competitive inhibitor. NMDA receptor signaling has been associated with the neurobiology of depression as a key component of CNS information processing. A placebo-controlled crossover pilot clinical trial randomized 20 patients ages 18–65 with treatment-resistant major depressive disorders without psychosis to either an admixture of up to a maximum of 50% nitrous oxide/50% oxygen (active treatment) or 50% nitrogen/50% oxygen for one hour (placebo). Patients in the active treatment arm experienced a significant improvement in depressive symptoms at two hours and 24 hours post-treatment vs. placebo, with the most significant changes seen in the symptoms depressed mood, guilt, suicidal ideation, and psychic anxiety. Although the study authors anticipated that depressive symptoms would revert to baseline after one week when patients returned for their second treatment session, several patients showed lower Hamilton Depression Rating Scale-21 scores after the one-week interval. Twenty percent of the patients receiving nitrous oxide had a treatment response and 15% experienced remission. These results should be interpreted with caution, as larger studies are needed to replicate the results and examine safety concerns like nitrous oxide’s inactivation of vitamin B12.
NMDA receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and NMDA receptor antagonist, may also be a rapidly acting treatment for TRD.