Laughing gas for treatment-resistant depression: no kidding


It sounds like a bad taste joke, but researchers found that nitrous oxide – otherwise known as laughing gas – dramatically improved symptoms in people with treatment-resistant depression.

In a phase 2 clinical trial, researchers at the Washington University School of Medicine in St. Louis demonstrated that symptoms of depression “improve rapidly” after treatment with inhaled nitrous oxide diluted with oxygen. .

Oddly enough, given that the effects of nitrous oxide wear off once exposure is stopped – which is why you can go home after leaving the dentist’s chair – study participants “reported that benefits can last for several weeks ”.

What were the researchers thinking?

About a third of people with depression are at risk for resistance to treatment, which is usually diagnosed when two different prescribed medications fail to improve symptoms.

In recent years, ketamine, a hallucinogenic drug and veterinary anesthetic, has been tested successfully as a revolutionary treatment for severe depression – but it carries risks of addiction and can have side effects such as amnesia.

When abused, especially as a party drug, it can actually cause depression.

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Ketamine works by blocking molecules on nerve cells called N-methyl-D-aspartate (NMDA) receptors – and it was thought that nitrous oxide could work the same way, without the risks of addiction or extreme side effects. ketamine.

Previous research by the same team

The study’s principal investigators were Dr. Charles R Conway, professor of psychiatry at the University of Washington, and Dr. Peter Nagele, MD, professor and chair of the Department of Anesthesia and Critical Care at the University of Chicago. .

In 2014, they conducted a proof of concept study that used a mixture of 50% nitrous oxide and 50% oxygen.

Participants with treatment-resistant depression were exposed for one hour to the laughing gas mixture or to a placebo.

The study reported “rapid and marked” antidepressant effects, but the 50-50 mixture caused nausea in some participants and headaches in others.

The new study

According to a statement from the University of Washington, the new study involved 24 patients.

Each received three treatments approximately one month apart.

During one session, the patients breathed for one hour gases composed of half nitrous oxide and half oxygen.

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During a second treatment, the same patients inhaled a 25% solution of nitrous oxide.

A third treatment, the placebo, consisted of breathing only oxygen, without nitrous oxide.

Indeed, the participants served as both experimental and control participants.

“You can’t really get a better comparison group than when you compare a person to themselves,” Dr. Nagele said.

“Being your own control is ideal. The alternative is to study the effects of a drug on two similar groups of people in which you receive one or another treatment. But the problem is, it takes a lot more patients before you can really draw any conclusions. “

The study found that nitrous oxide – both 25% and in a 50-50 mixture with oxygen – improved depression in 17 of the participants.

The 50-50 mix dose had greater antidepressant effects two weeks after treatment, but the 25 percent dose was associated with fewer adverse events, the most common of which was nausea.

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“It wasn’t until people were given the 50% dose that they felt nauseous,” Dr. Conway said.

“When they were given 25% nitrous oxide, no one developed nausea. And that lower dose was about as effective as the higher dose in relieving depression. “

Some participants were no longer clinically depressed

Of the 20 people who completed all of the study’s follow-up treatments and exams, 55 percent (11 out of 20) experienced significant improvement in at least half of their depressive symptoms, and 40 percent (eight out of 20) 20) were considered to be in remission – meaning they were no longer clinically depressed.

Overall, 85 percent (17 out of 20) of participants experienced “an improvement significant enough to shift their clinical classification from at least one category – for example, from severe depression to moderate depression.”

This is very promising, but nitrous oxide is usually given, like any anesthetic, as part of a designated procedure, not chronically.

The effects of prolonged use of laughing gas remain to be determined.


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