Inhaling a single, low dose of nitrous oxide, better known as “laughing gas,” helped “rapidly relieve” symptoms of severe depression in people whose condition does not respond to medication, according to a new study.
And to the researchers’ surprise, the effects lasted longer than two weeks; the experimental treatment was expected to last for about 24 hours.
Although laughter is supposed to be the best medicine, participants in the University of Chicago Medicine and Washington University study did not giggle their way to improvement. The dose was so low that they actually fell asleep, Dr. Peter Nagele, study co-author and chair of anesthesia and critical care at UChicago Medicine, said in a statement.
“They’re not getting high or euphoric; they get sedated,” Nagele added. The study was published Wednesday in the journal Science Translational Medicine.
The researchers said it’s challenging to get the scientific community to accept “non-traditional” treatments for depression like laughing gas, but the option could be ideal for people in a mental health crisis whose depression fails to respond to medications.
“There is a huge unmet need. There are millions of depressed patients who don’t have good treatment options,” especially those with suicidal thoughts, Nagele said. “If we develop effective, rapid treatments that can really help someone navigate their suicidal thinking and come out on the other side — that’s a very gratifying line of research.”
The team built their new study on a previous one that found a one-hour inhalation session with 50% nitrous oxide gas in 20 people led to quick improvements in symptoms of depression that lasted for at least 24 hours. The con: several people experienced negative side effects such as nausea, vomiting and headaches.
The researchers wondered if the high dose of laughing gas was causing the side effects, so in a follow-up experiment they tested a one-hour inhalation session with 25% of the gas.
“Maybe by lowering the dose, we could find the ‘Goldilocks spot’ that would maximize clinical benefit and minimize negative side effects,” Nagele said.
Turned out the lower dose was nearly as effective as the higher one, causing just one quarter of the negative side effects. And while the first study only evaluated how depressive symptoms changed over 24 hours, the new one continued for two weeks.
“The reduction in side effects was unexpected and quite drastic, but even more excitingly, the effects after a single administration lasted for a whole two weeks,” Nagele said. “This has never been shown before. It’s a very cool finding.”
Study co-author Dr. Charles Conway, a professor of psychiatry and the director of the Treatment Resistant Depression and Neurostimulation Clinic at Washington University School of Medicine, said about 15% of people with depression don’t respond to “standard antidepressant treatment.”
‘We don’t really know why standard treatments don’t work for them, though we suspect that they may have different brain network disruptions than non-resistant depressed patients,” Conway said in the statement. “Identifying novel treatments, such as nitrous oxide, that target alternative pathways is critical to treating these individuals.”