You might have been given laughing gas during a dental procedure, or even while giving birth — it's a mild sedative gas that slows down the nervous system and dulls pain, making patients feel more at ease and less inhibited. But now, it's showing promising results while treating depression. "The effects after a single administration lasted for a whole two weeks," Dr. Peter Nagele, MD, one of the study's co-authors and a professor of psychiatry and behavioral neuroscience at the University of Chicago, told Science Alert. "This has never been shown before. It's a very cool finding."
Doctors first looked into using laughing gas as an antidepressant in a 2015 proof-of-concept trial. That initial study proved that inhaling 50% nitrous oxide can be effective, but with his new research, Dr. Nagele wanted to investigate whether effects can be long-lasting and whether a smaller dosage can yield similar results. The study's co-authors confirmed that patients who inhaled 50% and 25% nitrous oxide experienced similar positive results, but the individuals who received a lower dosage reported fewer side effects.
"We need acceptance by the larger medical community for this to become a treatment that's actually available to patients in the real world," said Dr. Nagele. "Most psychiatrists are not familiar with nitrous oxide or how to administer it, so we'll have to show the community how to deliver this treatment safely and effectively.”
The co-authors were also galvanized by recent research that proves ketamine can alleviate symptoms of depression. While many traditional antidepressants work by increasing serotonin, which eventually impacts the neurotransmitter glutamate, ketamine targets the brain's N-methyl-D-aspartate receptors and allows new synapses to form in the frontal cortex. Because of this, ketamine works immediately.
"The speediness of ketamine in producing an antidepressant effect occurs because this drug bypasses the traditional serotonin route and goes directly to activating glutamate," Dr. Alexander Papp, MD told UC San Diego Health.
Dr. Nagele described the revelation as one of the biggest recent breakthroughs in depression research, and told Gizmodo that, because nitrous oxide has "similar mechanistic properties," researchers "hypothesized that nitrous oxide may also be an antidepressant." It can also be a less intense alternative to ketamine, which is often associated with trance-like hallucinations and can easily be abused.
This could be a game-changer for the many people who don't respond to other antidepressants. According to research published in the World Journal of Psychiatry, up to 15% of people diagnosed with depression don't respond to traditional medication, and around 35% say that antidepressants only offer partial relief. Individuals who don't respond to at least two different antidepressants — who, by and large, tend to be women and older people — might be diagnosed with treatment-resistant depression.
"One thing has become clear, especially after the success of ketamine: It is necessary to find different mechanisms of changing brain function in patients with depression," Dr. Madhukar Trivedi, director of the Center for Depression Research and Clinical Care at UT Southwestern Medical Center, told NBC News. "What has been developed by drugmakers in the past 25 years is not sufficient."