A single one-hour treatment with nitrous oxide - also known as laughing gas - can relieve symptoms of treatment-resistant depression for several weeks, according to a phase 2 clinical trial involving 28 participants. By showing that a 25% concentration of the gas still has therapeutic effects, the results suggest that lower concentrations of nitrous oxide could be useful against depression in the clinic while bringing a lower risk of side effects. Inhaled nitrous oxide is commonly used as a sedative agent in dental and medical offices, but the gas has also attracted attention as a possible treatment for depression. A previous study showed that nitrous oxide had marked antidepressant effects against treatment-resistant major depression, a severe form of depression that often fails to respond to standard antidepressants. However, this earlier study didn't evaluate the treatment's effects beyond 24 hours and used 50% nitrous oxide, a high concentration that can cause side effects such as nausea. 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 the course of 3 months, the 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. However, the sessions with 25% nitrous oxide also had a four-fold lower risk of adverse effects such as sedation, nausea, and mild dissociation. Although studies with larger patient groups are needed, Nagele et al. note that the responders showed a mean drop in depression scores that was larger than that seen in previous trials of traditional antidepressants.
Science Translational Medicine