Inhaled nitrous oxide is used as a sedative in dental and medical offices. A previous study showed that nitrous oxide had good antidepressant effect against treatment-resistant major depression.
Peter Nagele and colleagues investigated the safety and efficacy of a lower concentration of 25% nitrous oxide in 28 patients with treatment-resistant major depression.
Over 3 months patients received 3 one-hour inhalation sessions with a placebo, 25% nitrous oxide, and 50% nitrous oxide, in series, with each session separated by 4 weeks. After the 25% and 50% sessions, around 85% of the patients showed substantial improvements in their depression symptoms that lasted as long as four weeks.
Sessions with 25% nitrous oxide also had a four-fold lower risk of adverse effects such as sedation, nausea, and mild dissociation. More studies involving larger patient groups are needed, Nagele et al. note that the responders showed a mean drop in depression scores.