Low doses of 'laughing gas' could be effective treatment for
A new study found that a single inhalation session with 25% nitrous oxide gas was nearly as effective as 50% nitrous oxide at rapidly relieving symptoms of treatment-resistant depression, with fewer adverse side effects. The study, published in Science Translational Medicine, also found that the effects lasted much longer than previously suspected, with some participants experiencing improvements for upwards of two weeks.

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown.

In this phase 2 clinical trial, 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21).

- Whereas nitrous oxide significantly improved depressive symptoms versus placebo, there was no difference between 25 and 50% nitrous oxide.

- The estimated differences between 25% and placebo were ?0.75 points on the HDRS-21 at 2 hours, ?1.41 points at 24 hours, ?4.35 points at week 1, and ?5.19 points at week 2, and the estimated differences between 50% and placebo were ?0.87 points at 2 hours, ?1.93 points at 24 hours, ?2.44 points at week 1, and ?7.00 points at week 2.

- Adverse events declined substantially with dose.

Conclusively, these results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

Science Translational Medicine
Source: https://stm.sciencemag.org/content/13/597/eabe1376
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