Depression is not a laughing matter, but a new proof-of-concept study is providing the medical community with a ‘why didn’t we think of that’ moment. Most of us have been under the influence of laughing gas, or nitrous oxide, at the dentist. I know during my wisdom teeth extraction, I found damn near everything hilarious.

A team out of the Washington University School of Medicine in St. Louis decided to act on the sentiment. Why not treat a disease whose profound characteristic is sadness with something that makes you laugh?

Published in the journal Biological Psychiatry, the pilot study involved 20 patients with severe depression not responding to standard treatment protocols. The team, led by Peter Nagele, believes this is the first time depression patients were given nitrous oxide in a study.

“It’s kind of surprising that no one ever thought about using a drug that makes people laugh as a treatment for patients whose main symptom is that they’re so very sad.”

The laughing gas study was developed as a randomized, placebo crossover trial. Patients underwent two treatments, once with the control – a mixture of oxygen and nitrogen, and the other with laughing gas (nitrous oxide).

The active agent was the exact same formula dentists use as a sedative. Symptoms were measured both shortly after the trial, and a day later. Two-thirds of the patients receiving the nitrous oxide treatment reported better symptoms, compared to just one-third of the placebo treatments.

None of the patients reported worse symptoms after receiving the laughing gas treatment. In some encouraging news, but not measured, patients were reporting feeling better a full week after the treatment.

Why is this a big deal for depression patients? In the study, researchers point out that one-third of patients are not responsive to traditional depression treatments. Laughing gas has the added benefit of being safe. Side effects are few, and the gas leaves the body once you stop breathing it.

Charles Conway, associate professor of psychiatry and co-author, remarked on the study.

“When they received nitrous oxide, many of the patients reported a rapid and significant improvement. Although some patients also reported feeling better after breathing the placebo gas, it was clear that the overall pattern observed was that nitrous oxide improved depression above and beyond the placebo.”

Another benefit? It’s fast-acting. If you are under treatment for depression, you’ve probably heard the ‘two week’ rule thrown about. It’s the amount of time it takes for the drug treatment to have its maximum health benefit.

For patients with suicidal thoughts, two weeks may as well be a lifetime. If nitrous oxide can be a backstop of immediate treatment, it could change the way depression is treated in clinics and hospitals worldwide.

The team is currently moving on from the pilot study to test differing concentrations of laughing gas on depression symptoms. With the low number of side effects, maybe depression patients will one day have a silver bullet in managing their symptoms.


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