HealthDay News — For treatment-resistant major depression (TRMD), 25% nitrous oxide has comparable efficacy to 50% nitrous oxide, with a lower rate of adverse effects, according to a study published in the June 9 issue of Science Translational Medicine.

Noting that nitrous oxide at 50% inhaled concentration has improved depressive symptoms in TRMD, Peter Nagele, MD, from the University of Chicago, and colleagues examined the efficacy of 25 percent nitrous oxide in TRMD. Twenty-four patients with severe TRMD were randomly assigned to a 1-hour inhalation with 50% nitrous oxide, 25% nitrous oxide, or placebo.

The researchers found that nitrous oxide significantly improved depressive symptoms vs placebo (P =0.01) but no difference was seen between 25 and 50% nitrous oxide (P =.58). The estimated differences on the Hamilton Depression Rating Scale were −0.75 (P =.73), −1.41 (P =.52), −4.35 (P =.05), and −5.19 points (P =.02) at 2 hours, 24 hours, 1 week, and 2 weeks, respectively, between 25% nitrous oxide and placebo. For 50% nitrous oxide and placebo, the corresponding estimated differences were −0.87 (P =.69), −1.93 (P =.37), −2.44 (P =.25), and −7.00 points (P =.001). There was a substantial decline in adverse events with the lower dose (P <.001).

“The reduction in side effects was unexpected and quite drastic, but even more excitingly, the effects after a single administration lasted for a whole two weeks,” Nagele said in a statement. “This has never been shown before. It’s a very cool finding.”


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Several authors disclosed financial ties to the pharmaceutical industry; one author has previously filed for intellectual property protection related to the use of nitrous oxide in major depression.

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