Low doses of nitrous oxide — commonly referred to as “laughing gas” — can relieve symptoms of treatment-resistant depression for up to two weeks, a study shows.
Experts led by the University of Chicago found that an hour-long session inhaling 25 percent nitrous oxide was almost as effective as the same with a 50 percent mixture.
In addition, the reduced dose was found to cause fewer unwanted side effects, while providing benefits for longer than the team had expected.
The team said the findings add to evidence that nontraditional treatments may be viable in cases where patients fail to respond to antidepressants.
In addition, they noted that nitrous oxide could be a rapidly effective treatment option for patients with depression who are in crisis.
Nitrous oxide is best known for its use as an anesthetic and provides short-term pain relief during dental and surgical procedures.
Due to its euphoric potential, it is also inhaled as a recreational drug and is known by several names, including “NOS,” “sweet air,” and “hippy crack.”
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Low doses of nitrous oxide — commonly referred to as “laughing gas” — can relieve symptoms of treatment-resistant depression for up to two weeks, a study shows. Nitrous oxide is best known for its use as an anesthetic and provides short-term pain relief during dental and surgical procedures, as pictured (stock image)
Laughing gas or ‘laughing gas’ is a colorless gas that has a euphoric effect when inhaled.
That is why it has been used since 1844 as a pain-reducing anesthetic for patients undergoing dental or surgical procedures – usually in a 50/50 mixture with oxygen.
Due to its euphoric potential, it is also inhaled as a recreational drug.
The recent work built on an earlier study in which the researchers tested the effects of an hour-long inhalation session of 50 percent nitrous oxide on 20 patients.
Although this treatment led to a rapid improvement in depressive systems compared to a placebo, it was found to last only about 24 hours and several subjects had negative reactions, including headache, nausea and vomiting.
“This research was motivated by observations of research on ketamine and depression,” said study author and trauma anesthesiologist Peter Nagele of the University of Chicago.
“Like nitrous oxide, ketamine is an anesthetic, and there has been promising work using ketamine at a subanesthetic dose to treat depression.”
‘We wondered if our concentration of 50 percent hadn’t been too high in the past. Perhaps by lowering the dose we can find the ‘Goldilocks spot’ that would maximize the clinical benefit and minimize the negative side effects.”
Accordingly, Dr. Nagele and colleagues in their latest study developed a similar protocol, recruiting 24 patients with treatment-resistant major depression.
Each patient received a single hour-long inhalation session containing 50 percent nitrous oxide, 25 percent nitrous oxide, or a placebo.
The team found that — although it was half the concentration — the 25 percent treatment was nearly as effective as the 50 percent mixture, but it came with a three-quarter reduction in negative side effects.
In this study, the researchers also conducted a more substantial follow-up, monitoring patients two weeks after treatment instead of the 24 hours of the previous study.
“The reduction in side effects was unexpected and quite drastic,” says Dr. Nagele.
‘But even more exciting was that the effects lasted for up to two weeks after a single administration. This has never been seen before. It’s a very cool finding.”
Despite its reputation, the patients in the study were given such low doses of nitrous oxide that they basically just fell asleep, instead of giggling for an hour.
“They don’t get high or euphoric, they get numb,” explains Dr. Nagele.
Based on the findings, nitrous oxide could be used to treat individuals whose depression does not respond to other treatments, such as selective serotonin reuptake inhibitors (SSRIs), a common form of antidepressant drug.
“A significant percentage – we think about 15 percent – of people who suffer from depression do not respond to standard antidepressant treatment,” says author and psychiatrist Charles Conway of Washington University in St. Louis, Missouri.
“These ‘treatment-resistant depression’ patients often suffer from life-threatening depression for years, even decades.”
“We don’t really know why standard treatments don’t work for them, although we suspect they have different brain network disturbances than non-drug resistant depressed patients.”
“Identifying new treatments, such as nitrous oxide, that target alternative routes is critical to treating these individuals,” he concluded.
“A significant percentage — we think about 15 percent — of people who suffer from depression do not respond to standard antidepressant treatment,” says psychiatrist Charles Conway of Washington University in St. Louis, Missouri. He concluded: ‘Identifying new treatments, such as nitrous oxide, that target alternative routes is critical to treating these individuals.’ Pictured: Citalopram tablets are commonly prescribed for depression
The researchers said they hope their findings will help patients who are currently struggling to find adequate therapies to help with their depression.
‘These are just pilot studies. We need acceptance by the wider medical community for this to become a treatment that is 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 will have to show the community how this treatment can be given safely and effectively. I think there will be a lot of interest in getting this into clinical practice.”
“There are millions of depressed patients who don’t have good treatment options, especially those dealing with suicidality.”
“If we develop effective, rapid treatments that can really help someone navigate through their suicidal thoughts and come out on the other side, that’s a very satisfying line of research,” he concluded.
The study’s full findings were published in the journal Science Translational Medicine.
DEPRESSION AFFECTS ONE IN TEN PEOPLE AT ONE POINT
While it’s normal to feel down from time to time, people with depression can feel persistently unhappy for weeks or months.
Depression can affect anyone at any age and is quite common – about one in ten people are likely to experience it at some point in their lives.
Depression is a real health condition that people can’t just ignore or ‘get out’.
Symptoms and effects vary, but may include feeling constantly upset, hopeless, or losing interest in things you used to enjoy.
It can also cause physical symptoms, such as trouble sleeping, fatigue, a low appetite or sex drive, and even physical pain.
In extreme cases, it can lead to suicidal thoughts.
Traumatic events can cause it, and people with a family history may be more at risk.
It’s important to see a doctor if you think you or someone you know has depression, as it can be treated with lifestyle changes, therapy, or medication.
Source: NHS Choices