It is somewhat surprising that nobody has thought to treat an illness where the main symptom is profound sadness with a substance that makes people laugh. Such was the sentiment expressed by the head of a team that conducted a small pilot study that found nitrous oxide - commonly known as laughing gas - shows promise in alleviating severe depression that is not responding to treatment.

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Researchers behind a new pilot study suggest laughing gas may offer temporary relief from symptoms while patients with depression wait for longer term treatment to show results.

The team, from Washington University School of Medicine in St. Louis, MO, reports the findings of their proof-of-concept study into the effects of laughing gas on severe, treatment-resistant depression in the journal Biological Psychiatry.

They believe it is the first study where patients with depression have been given nitrous oxide or laughing gas, a fact that lead researcher Peter Nagele, assistant professor of anesthesiology, remarks on:

"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 study involved 20 patients with severe depression whose illness was not responding to conventional treatment.

It was a randomized, placebo-controlled crossover trial where the participants underwent two treatments: once with the active drug - the laughing gas or nitrous oxide - and once with a placebo, on separate occasions. They were randomly assigned to receive either the drug or the placebo first.

The active drug was a mixture of half oxygen and half nitrous oxide - the same mixture that dentists give to patients as a sedative agent. The placebo was a mixture of oxygen and nitrogen, the two main gases in the air we breathe.

Symptom severity was evaluated shortly after the treatments, and then on the day after. This was by means of a survey that examined items like sadness, feelings of guilt, suicidal thoughts, anxiety and insomnia.

Two-thirds of patients reported improved symptoms after treatment with laughing gas

The results showed that two-thirds of the patients reported an improvement in symptoms after receiving the nitrous oxide. In contrast, only one-third of the same patients reported improvement after receiving the placebo treatment. And none of the patients reported worse symptoms after treatment with nitrous oxide.

Despite the fact they only evaluated the symptoms twice in 24 hours, the team is encouraged by the findings, as Prof. Nagele explains:

"Our findings need to be replicated, but we think this is a good starting point, and we believe therapy with nitrous oxide eventually could help many people with depression."

In their background information, the authors note that currently up to one-third of patients with clinical depression do not respond to current therapies, pointing to a need for more effective treatments.

Among the reasons that attracted them to laughing gas is the fact it has few side effects - mostly limited to nausea and vomiting - and it leaves the body soon after you stop breathing it.

It was this last point that convinced the researchers the improvement in symptoms measured 24 hours after treatment was real and not just a side effect of the gas.

And - although this was not formally measured - some of the patients said they were still feeling better a week later.

Co-author Charles R. Conway, associate professor of psychiatry at Washington University, says:

"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."

Laughing gas could be useful as a fast-acting reliever of depression symptoms

Prof. Conway says most of the participants who showed improvement reported feeling better only two hours after receiving nitrous oxide. This compares with "at least 2 weeks for typical oral antidepressants to exert their beneficial, antidepressant effects," he notes.

If the findings can be replicated, it would be very useful to have such a fast-acting drug, particularly to give to patients at risk of suicide - for them, 2 weeks could be a very long time to wait for improvement. Such a drug might also be used to relieve symptoms temporarily until more conventional treatment takes effect.

The team is shortly starting a new series of studies to test the effects of different concentrations of laughing gas on symptoms of depression.

The researchers presented their study results at the recent annual meeting of the American College of Neuropsychopharmacology in Scottsdale, AZ.

Funds for the study came from Washington University's Departments of Anesthesiology and Psychiatry and Taylor Family Institute for Innovative Psychiatric Research.

In November 2014, Medical News Today brought news of another study where researchers suggest how the brain manages stressoffers a new model of depression. Writing in the journal Nature, a team from Icahn School of Medicine at Mount Sinai says the brain's ability to deal with stress - or be more susceptible to depression - depends on a single type of protein in each person's brain.