Lower dose laughing gas effectively improves symptoms of treatment-resistant depression: Study

USA: A single one-hour treatment with 25% nitrous oxide (laughing gas) is equally effective as 50% nitrous oxide for improving treatment-resistant depression but with a lower risk of adverse effects, show results from a phase 2 trial. The treatment with 25% of the gas helped in relieving symptoms of treatment-resistant major depression (TRMD) for several weeks. 

The results of the study, published in the journal Science Translational Medicine, 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.

Reference:

The study titled, "A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression," is published in the journal Science Translational Medicine.

DOI: https://stm.sciencemag.org/content/13/597/eabe1376