Clinical Research Directory

Inclusion criteria: * Ability to give written informed consent * Moderate to severe suicidal ideation defined as a score ≥3 on the Montgomery-Asberg Depression Rating Scale (MADRS; Schmidtke et al., 1985) suicide item (item #10) as well as a self-report Beck Scale for Suicide Ideation (BSS; Kliem et al., 2017) items #4 plus #5 score ≥ 2 * Plasma homocysteine level ≤ 14 µmol/l Exclusion criteria: * Organic, including symptomatic, mental disorders (F00-F09; lifetime diagnosis) * Schizophrenia, schizotypal and delusional disorders (F20-F29; lifetime diagnosis) * Mental and behavioral disorders due to psychoactive substance use. Nicotine and cannabis will be ignored (F10-F19) * Non-medical (i.e., recreational) use of inhalational N2O during the last 12 months * Past intolerance or hypersensitivity to N2O * Critical illness * Severe cardiac disease * Pregnancy or breastfeeding * Pulmonary hypertension * Chronic cobalamin or folate deficiency unless treated with folic acid and/or vitamin B12 * History or evidence of any other medical or neurological condition that would expose the subject to an undue risk of a significant adverse event as determined by the clinical judgment of the investigator * Treatment with ketamine/esketamine during the last 4 weeks * Treatment with opioid medications during the last 3 months * Treatment with vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT) within the last 3 months * Recent (within the last 4 weeks) or current use of benzodiazepines in excess of 5 mg lorazepam or equivalent per day * Finally, any other factors that, in the investigator's judgment, would unduly impact patient safety or compliance during the study.