Inhalational nitrous oxide as a transdiagnostic approach for the treatment of suicidal ideation and suicidality in psychiatric inpatients: protocol for a double-blind randomised, controlled clinical single-centre trial.

Abstract

Suicidal thoughts and behaviours are linked to a wide range of mental health conditions. New interest in the psychiatric benefits of nitrous oxide (N₂O) has only recently emerged. The broad pharmacological effects of N₂O are thought to be due in large part to N-methyl-d-aspartate antagonism and opioid effects. The purpose of this study protocol is to test whether inhalational N₂O exerts rapid antisuicidal effects as a transdiagnostic treatment for suicidal ideation. This is the protocol of a single-centre pilot study of N₂O inhalation in 85 psychiatric inpatients. The initial 45-min double-blind, randomised, placebo-controlled inhalation session either consists of 50% N₂O and 50% oxygen ('active treatment') or 50% oxygen plus air. The primary outcome is the change in Beck Scale for Suicidal Ideation scores between the day before and the day after inhalation. A second inhalation containing N₂O will be administered 1 week after the first inhalation to ensure that all study participants receive the active treatment at least once. For the mechanism of action and prediction, a nested biomarker substudy will employ multimodal techniques, including analysis of hair and blood samples and electroencephalography. This study was approved by the local ethics committee ('Kantonale Ethikkommission-Kanton Zürich') and by the Swiss Agency for Therapeutic Products (Swissmedic). Study results will be disseminated primarily by peer-reviewed scientific journals and also by conference presentations, patient and public events and social media. ClinicalTrials.gov ID NCT06636357.