Nitrous Oxide in the Treatment of Acute Suicidal Ideation

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.