The study, at Washington University School of Medicine in St Louis, is believed to be the first research in which patients with depression were given laughing gas.
In 20 patients who had treatment-resistant clinical depression, the researchers found that two-thirds experienced an improvement in symptoms after receiving nitrous oxide.
In comparison, one-third of the same patients reported improved symptoms after treatment with a placebo. The patients were evaluated on the day of and day after each treatment.
"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," said principal investigator Peter Nagele, assistant professor of anaesthesiology at the School of Medicine.
As many as one-third of patients with clinical depression do not respond to existing treatments, which points to the need to develop more effective therapies.
Laughing gas is attractive because its side effects are limited - the most common are nausea and vomiting - and it leaves the body very quickly after people stop breathing the gas. Researchers believe the improvement in symptoms a day
They cite an anecdotal finding from the study that the improvements lasted for at least one week in some patients. As part of the study, patients received two treatments, but neither the subjects nor the researchers knew the order in which those treatments were given.
In one session, patients were given a gas mixture that was half oxygen and half nitrous oxide — the same mixture dentists give to patients undergoing dental procedures.
In a second session, the patients received a placebo mixture of oxygen and nitrogen, the two main gases in the air we breathe.
Two hours after each treatment, and again the next day, the study subjects were surveyed about the severity of their symptoms, such as sadness, feelings of guilt, suicidal thoughts, anxiety and insomnia.
One day after nitrous oxide treatment, seven patients reported mild improvement in their symptoms, while another seven reported significant improvement.
Three patients reported that their symptoms had disappeared almost completely. No patients said their symptoms worsened after treatment with nitrous oxide.
"When they received nitrous oxide, many of the patients reported a rapid and significant improvement," said co-investigator Charles R Conway, associate professor of psychiatry.