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Laughing gas holds promise for treatment-resistant depression, small trial finds


Laughing gas has been used to relieve pain in dental offices and maternity wards for over a century, but researchers now believe the gas, called nitrous oxide, can effectively treat depression when other therapies have failed. .

That’s according to the results of a small phase 2 clinical trial, published Wednesday in the journal Science Translational Medicine.

Up to 30 percent of people diagnosed with major depressive disorder do not respond to typical treatments, leaving a significant portion of patients in need of new treatment options.

The landscape for these patients began to change in 2019, when the Food and Drug Administration approved therapy for treatment-resistant depression based on the anesthetic ketamine. It works by blocking N-methyl-D-aspartate receptors in the brain, which have been linked to major depressive disorder. Traditional antidepressants work on serotonin receptors in the brain.

“The discovery of ketamine is considered one of the biggest breakthroughs in depression research in 50 years,” said lead co-author of the new study, Peter Nagele, professor of psychiatry and behavioral neuroscience and president of anesthesia and intensive care at the University of Chicago.

Nitrous oxide is believed to work the same way as ketamine, Nagele said.

The new study expanded on an earlier proof-of-concept trial, which showed that inhaling 50 percent nitrous oxide – the amount typically used for pain management during medical procedures – reduced symptoms depressive in people resistant to other treatments. Nagele and the other co-authors wanted to know if these effects last for a long time and if a lower dose of gas could produce the same results with fewer side effects.

The trial included 24 participants. Over 70 percent were female, 96 percent were Caucasian, and all suffered from treatment-resistant depression. Twenty participants completed the full trial, which involved receiving two doses – at concentrations of 25 percent and 50 percent – of nitrous oxide and a placebo in random order over three months. Each session lasted one hour.

According to one of the three measures of depression used to measure progress, the lower dose of nitrous oxide appeared to have a similar effect to the higher dose, but with fewer side effects, which usually included headache, nausea and tingling. The effects also seemed to last up to two weeks in some patients.

However, the study is far from definitive.

“The main limitation is that this is a very small study,” said Ravi Das, research psychopharmacologist at University College London.

Each participant received all three treatments, as opposed to a randomized controlled clinical trial, where one group received the treatment and the other a placebo. While this design allowed researchers to compare people to themselves rather than to other people, it may also have clouded the results, as a lasting effect of one treatment may have improved the results of another. , said Das.

Despite its shortcomings, Das believes the new trial adds to a promising body of research that has explored nitrous oxide as a potential treatment for depression.

“What I would like to see is the comparison to ketamine. If they produced similar effects, I would use nitrous oxide every time, ”he said, noting that both drugs are cheap and easy to administer, but that nitrous oxide generally has milder side effects.

“One thing has become clear, especially after the success of ketamine: there is a need to find different mechanisms of altering brain function in patients with depression,” said Madhukar Trivedi, director of the Center for Depression Research and Clinical Care. of UT Southwestern Medical Center in Dallas, which was not involved in the lawsuit. “What has been developed by drug manufacturers over the past 25 years is not enough.”

The next step, Nagele says, is to conduct a larger trial that includes hundreds of patients. “We have to be sure that it works and also understand why it might not work in some patients,” Nagele said.

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