Laughter is the best medicine. Fairly old adage. Probably still has some real relevance. Um, interesting work out of the Netherlands. A single inhalation of nitrous oxide was associated with significant, rapid, and sustained improvement of treatment-resistant depression in older adults. Nitrous oxide is laughing gas.
Depression symptoms decrease within 24 hours of receiving treatment by face mask, and we’ll put the link in the description as usual. Those who received nitrous oxide showed a clinically meaningful decrease in depression scores compared to placebo.
The study adds to a growing body of research that points to a possible benefit from laughing gas in people with depression. Now this work was done on older people. Previously, there’d been some studies done on people with a median age of 39. This one: 60 participants, median age of 72, no history of cognitive impairment, and look again essentially reduction in depression markers, and people felt better. These positive findings were supported by both clinician and self-rated questionnaires.
Side effects were mild and transient. Adverse effects again relatively minor, not zero, but relatively minor.
It’s not absolutely clear whether antidepressant effects are possible with a shorter duration of action. Keeping in mind, this went for an hour. However there’s been some experimental work showing that patients responded well to a 20-minute blast of nitrous oxide.
This is really very interesting for a number of reasons. We know that when we’re laughing, we’re not going to feel down or bad. It is actually technically impossible to feel depressed while you are laughing. Now, when you stop laughing, you might revert to how you were before, but laughter does release the body’s own endorphins or happy hormones. It does tend to slightly slow down our pulse and our blood pressure, and our breathing rates. And all these things are connected. It gets us out of fight or flight mode, which is very, very positive.
But when we are laughing, we’re not thinking about anything else because actually, we almost can’t. We can stop, we can try and physically stop ourselves laughing, and then try to think about what’s worrying us, and you know, obviously, people may do that, and at some point, you stop laughing. But what was interesting to me in this particular study was that the effects were ongoing for a period of time. Now, a few weeks is probably not a long time, and I think it’d be interesting to see how people are after a month or six months.
But there are a number of other clinic-based depression treatments that also need to be repeated periodically. So one might need to go for a series of nitrous oxide or laughing gas inhalations, maybe over some months. And again, a protocol has not been worked out.
Well, that’s probably doable. It’s not a particularly expensive treatment. Nitrous oxide is fairly freely available. It’s not patentable. It’s just a gas — nitrous oxide. And it’s fairly old; it’s been around for a long time.
Contrast that perhaps with some newer treatments, and I don’t really want to mention it by name, but there are a couple that have taken some vogue recently. And they are useful, and I’ve personally seen people do quite well with them, but a lot of the newer treatments are very expensive because they’re new and just the nature of what they are. But this isn’t.
The next question, unfortunately, arises: how much notice will be paid to this, and what will be the follow-through? If this were a looming new medication that had a reasonably positive response to treatment-resistant depression — now treatment-resistant means it hasn’t responded to other treatments — we’re talking about people who failed other, including conventional, treatments. It would certainly be all across the medical news wires and might even leak into the lay media because this is of interest. A lot of people do struggle with mental health problems, including depression.
But it doesn’t because nobody’s pushing it or backing it. And for that reason, unfortunately, this may take a little bit of time to get up off the ground. But hopefully — and keep your eyes peeled on this space — this is an instance where we do need more work.
Now, often with research, they say, “Oh, we need more studies,” which is just code for “we want to get more grants so we can do more work.” This one, no — there aren’t actually really any protocols, and I think we need to know what the effects would be like after 6 and 12 months, and how many treatments people might need on average. People are going to be different. And yes, might there be more issues with adverse effects if more treatments are taken? And what is the optimum length of time? An hour is not excessive, but if 30 or 40 minutes would do it, then that would be even better. People are busy, and there’s a greater capacity to see more people if that is the case.
But the fact that it is fairly simple and that the side-effect profile is mild, and that the results are encouraging would hopefully encourage more looking into this. And that would include governments that sort of bleat about how concerned they are about the mental health crisis and the well-being of the citizens. This would be an area where they could actually throw a little bit of money and support behind it to see whether it has value. And as we sit here today, we can’t absolutely say — encouraging, but that’s about as far as we can go.
One other point out of the medical news wires on a slightly different tack. Now, we know that exercise is good for mental health as well. A lot of work shows that people who do regular exercise are less prone to anxiety and depression. But there’s a lot of argument about the number of steps. And we’ve spoken previously on the podcast about how the 10,000 steps was a marketing campaign from a Japanese company in the 1960s. And look, if you want to do 10,000 steps, go for it — not knocking it. But if you only get to 8,000, don’t stress about it. The fact that you’re doing some exercise is good and obviously, if you can do a little bit more, that’s better, but you’ve got to fit it into your 24 hours.
In the 1990s, pain — we’re just going to digress for a moment — pain was classed as the fifth sign. Pain is not a sign. It is a symptom. Pulse, blood pressure, breathing rate and temperature are signs. They are objectively measurable. They are not symptoms. Pain is a symptom. It’s something you feel. It’s not something that’s measured externally. Yes, you can do a questionnaire, but it’s not a sign.
Somebody wants to make step count the fifth vital sign. It is not a sign. It is not a physical sign. It’s a recording. You would think that people who studied medicine would get that. You really would — but you’d be wrong.
Is it a proxy for how much exercise people might be doing? Yeah, it might be. But guess what? Some people might ride a bike rather than walk. And I’m not sure, and I could stand corrected, whether bike riding registers as steps. Some people might swim — that may or may not register as steps. There are lots of forms of exercise that people can do. As we’ve said before, the exact number of steps is of interest but not absolutely critical. So the idea that steps are going to be a vital sign is just… who comes up with this stuff? So that’s one for the bin. We won’t do a separate podcast on that.
But in terms of improving mental health, certainly exercise is good. And in the southern hemisphere, we’re going into summer, so if you can dust off your exercise gear, it’s a better time of year to get outside and do some exercise. Inside as well is fine. If you’re in the gym, it’s good. Good for your physical and mental health.
And to wind it back to where we started, hopefully — and we’ll see — hopefully, a really simple and not particularly expensive treatment such as nitrous oxide/laughing gas may be an additional string to our bow in trying to help people with treatment-resistant depression.
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Dr Joe Kosterich – Doctor, Health Industry Consultant and Author
Doctor, speaker, author, and health industry consultant, Joe is WA State Medical Director for IPN, Clinical editor of Medical Forum Magazine, Medical Advisor to Medicinal Cannabis company Little Green Pharma and Course Chair, and writer for Health Cert. He is often called to give opinions in medico-legal cases, has taught students at UWA and Curtin Medical schools and been involved in post graduate education for over 20 years.
A regular on radio and TV, Joe has a podcast – Dr Joe Unplugged, has self- published two books and maintains a website with health information. He has extensive experience in helping businesses maintain a healthy workforce.
Past Chairman of Australian Tobacco Harm Reduction Association, current Vice President of Arthritis and Osteoporosis WA, Joe previously held senior positions in the Australian Medical Association and has sat on numerous boards.
