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Inhaled Nitrous Oxide Explored for Treatment-Resistant Depression

THURSDAY, June 10, 2021 -- For treatment-resistant major depression (TRMD), 25 percent nitrous oxide has comparable efficacy to 50 percent 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 percent inhaled concentration has improved depressive symptoms in TRMD, Peter Nagele, M.D., 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 one-hour inhalation with 50 percent nitrous oxide, 25 percent nitrous oxide, or placebo.

The researchers found that nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01) but no difference was seen between 25 and 50 percent nitrous oxide (P = 0.58). The estimated differences on the Hamilton Depression Rating Scale were −0.75 (P = 0.73), −1.41 (P = 0.52), −4.35 (P = 0.05), and −5.19 points (P = 0.02) at two hours, 24 hours, one week, and two weeks, respectively, between 25 percent nitrous oxide and placebo. For 50 percent nitrous oxide and placebo, the corresponding estimated differences were −0.87 (P = 0.69), −1.93 (P = 0.37), −2.44 (P = 0.25), and −7.00 points (P = 0.001). There was a substantial decline in adverse events with the lower dose (P < 0.001).

"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."

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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