Nitrous oxide interacts with NMDA glutamate receptors on brain cells and can improve symptoms of depression within hours when effective. Image courtesy of Shutterstock
By Jim Dryden
In a phase 2 clinical trial, researchers at Washington University School of Medicine and the University of Chicago demonstrated that symptoms of depression can improve rapidly following a single, one-hour treatment with inhaled nitrous oxide.
The study involved 24 participants. Each one received three treatments about one month apart. In one session, study participants breathed gas for an hour that was half nitrous oxide, half oxygen. In a second treatment, they breathed a solution that was 25% nitrous oxide. A third treatment, the placebo, involved breathing only oxygen, with no nitrous oxide. The trial’s findings were published in the journal Science Translational Medicine on June 9, 2021.
“A large percentage of patients don’t respond to standard antidepressant therapies—the patients in this study had failed an average of 4.5 antidepressant trials—and it’s very important to find therapies to help these patients,” says Charles Conway, MD, Washington University psychiatrist at Barnes-Jewish Hospital and the study’s co-senior investigator. “That we saw rapid improvements in many such patients in the study suggests nitrous oxide may help people with really severe, resistant depression.”
Conway and Peter Nagele, MD, the trial’s other co-senior investigator, have been studying the potential of nitrous oxide as an antidepressant for the past decade. Nagele is chair of the Department of Anesthesia & Critical Care at the University of Chicago; previously, he had an appointment in the Department of Anesthesiology at Washington University School of Medicine.
Standard antidepressant drugs affect norepinephrine and serotonin receptors in the brain, yet they often take weeks to improve a person’s symptoms. Nitrous oxide, however, interacts with different receptors on brain cells, called NMDA glutamate receptors, and tends to improve symptoms within hours when effective.
As many as one-third of people who take antidepressants don’t improve. Nitrous oxide and ketamine, another anesthetic drug that interacts with NMDA glutamate receptors, recently have shown promise in those with treatment-resistant depression. Nitrous oxide, however, may have some practical advantages over ketamine.
“One potential advantage to nitrous oxide, compared with ketamine, is that because it’s a volatile gas, its anesthetic effects subside very quickly,” Conway says. “It’s similar to what happens in a dentist’s office when people drive themselves home after getting a tooth pulled. After treatment with ketamine, patients need to be observed for two hours following treatment to make sure they are OK, and then they have to get someone else to drive them.”
“Our primary goals in this study were twofold: to determine whether a lower dose of nitrous oxide might be just as effective as doses we’d tested previously—and it was for most patients—and we also wanted to see how long the relief lasted,” Nagele says. “In a proof-of-concept study several years ago, we assessed patients for 24 hours. In this study, we continued to assess them for two weeks, and most continued to feel better.”
Originally published by Washington University School of Medicine at medicine.wustl.edu/news