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Laughing Gas Studied as Depression Treatment

Investigators say they’re encouraged by the results

Nitrous oxide (NO) –– commonly known as “laughing gas” –– has shown early promise as a potential treatment for severe depression in patients whose symptoms don’t respond to standard therapies. The pilot study, conducted 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.

The findings were published online December 8 in Biological Psychiatry.

In the study, 20 patients received two treatments, but neither the subjects nor the researchers knew the order in which those treatments were given. In one session, the patients received a gas mixture that was half oxygen and half NO — the same mixture dentists give to patients undergoing dental procedures. In a second session, the patients received a placebo mixture of half oxygen and half nitrogen, the two main gases in the air we breathe.

The mean duration of NO treatment was 55.6 minutes at a median inspiratory concentration of 44%. The treatment was briefly interrupted in two patients and was discontinued in three patients.

Two hours after each treatment, and again the next day, the subjects were questioned about the severity of their symptoms, such as sadness, feelings of guilt, suicidal thoughts, anxiety, and insomnia.

One day after NO treatment, seven patients reported mild improvements in their symptoms, whereas another seven reported significant improvements. Three patients reported that their symptoms had disappeared almost completely. No patients said their symptoms worsened after treatment with NO.

After receiving placebo, one patient reported worsened symptoms the next day; five reported mild improvements; and two reported that they felt significantly better.

“When they received nitrous oxide, many of the patients reported a rapid and significant improvement,” said co-investigator Charles R. Conway, MD. “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. Most patients who improved reported that they felt better only 2 hours after treatment with nitrous oxide. That compares with at least 2 weeks for typical oral antidepressants to exert their beneficial, antidepressant effects.”

Although the researchers evaluated the effects of the treatment only twice over a 24-hour period, they say that they are encouraged by the results.

“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, MD.

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. According to the authors, laughing gas is attractive because its side effects are limited — the most common are nausea and vomiting — and because it leaves the body very quickly after people stop breathing the gas.

That is why the researchers believe that the improvement in symptoms a day later was real and not a side effect of the NO. Further, they cite an anecdotal finding from the study that the improvements lasted for at least 1 week in some patients.

With standard antidepressants, such as Prozac (fluoxetine), Zoloft (sertraline), Lexapro (escitalopram oxalate), and other selective serotonin reuptake inhibitors (SSRIs), patients and their doctors often wait several days or weeks before they know whether the treatments are working. Moreover, the effects of treatments such as cognitive behavior therapy often aren’t obvious for weeks.

“If our findings can be replicated, a fast-acting drug like this might be particularly useful in patients with severe depression who may be at risk for suicide and who need help right away,” said co-investigator Charles F. Zorumski, MD. “Or perhaps the drug could be used to relieve symptoms temporarily until more conventional treatments begin to work.”

Sources: Washington University in St. Louis; December 9, 2014; and Biological Psychiatry; December 8, 2014.

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