A new study finds that a drug that makes people laugh may also reduce their depression.
A pilot study has found that nitrous oxide, or “laughing gas,” may be a potential treatment option for treatment resistant severe depression.
Researchers at Washington University School of Medicine in St. Louis, believe their study is the first in which patients with depression were given laughing gas.
In a group of 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.
The findings were presented at the annual meeting of the American College of Neuropsychopharmacology and were published online in the journal Biological Psychiatry.
Although the researchers evaluated the effects of the treatment only twice over a 24-hour period, 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, M.D., assistant professor of anesthesiology.
Experts note that as many as one-third of patients with clinical depression do not respond to existing treatments. The poor outcomes point 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 its relative safety as it leaves the body very quickly after people stop breathing the gas.
That’s why the researchers believe the improvement in symptoms a day later is real and not a side effect of the nitrous oxide. Further, 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.
Meanwhile, after receiving the placebo, one patient reported worse 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, M.D., associate professor of psychiatry.
“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 two hours after treatment with nitrous oxide. That compares with at least two weeks for typical oral antidepressants to exert their beneficial, antidepressant effects.”
Current use of standard antidepressants — such as Prozac, Zoloft, Lexapro, and other selective serotonin reuptake inhibitors (SSRIs) — requires patients and their doctors to often wait several days or weeks before they know whether treatments are working.
Similarly, the effects of treatments such as cognitive behavior therapy also 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, M.D.
“Or perhaps the drug could be used to relieve symptoms temporarily until more conventional treatments begin to work.”
The researchers said more studies are needed to learn whether nitrous oxide has the same benefits in other patients with depression. They also plan to test various concentrations of laughing gas to see how each influences symptoms of depression. Those studies will begin soon.
“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,” Nagele said.