Today, we're talking about something we see in clinic every single day, managing comorbid depression in our patients with chronic illnesses. So, if you've ever worked in primary care, then you've seen countless of these exact patients. And the stakes are pretty high because patients with chronic diseases have a 1. 5 to 3. 5 greater risk of developing depression compared to healthy folks. And it's not just about the mood, though. This comorbidity also increases their mortality risk by 1. 3 to threefold as well. And so there's a lot on the line. And as clinicians, what do we usually do? Well, if we get in the situation, we say, ah, here's some physical activity guidelines, try to do it. Right. So the guidelines are 150 minutes of moderate activity and two days of resistance training. I will mention that as well. Or what other guidelines in the WHO mentioned are 450 minutes per week. And so. You hear that and you might be like, Well, what's a met? That doesn't mean anything to me, Jordan. And yes, mets are confusing, but let's break it down real quick. It's important. So, Mets They are measuring intensity, right? So these are metabolic equivalents. A meta one means like you're just existing. That's just like you at baseline, or I shouldn't say you, some random person that they measured initially, but that's at baseline. And they measure intensity, right? How hard someone is working. So, a brisk walk is something like a three-med activity. And then, on top of that, we have minutes, right? So, they measure how long you're doing it or your duration. And then Met Minutes is just measuring your total volume. So your overall exercise activity for the week. So you're measuring how intense it was for how long you did it. And so, if you take the classic public health guidelines of 150 minutes of moderate activity, so that brisk walking, multiply it by the intensity of three meds, that's 150 minutes. By three mets would be 450 mets. So take a step back. They recommend 150 of moderate. Yep, that's great. Add a three-met, okay, three-met activity, 150 times three, that's 450 mets. So that's where those come from. That essentially comes down to 30 minutes of brisk walking five times per week. That's the general recommendations. I just wanted to just wanted to mention that. But I do want to stop here for a second. These can be patients that we're talking about. In our patient, in our clinics, that have heart failure, MS, diabetes, undergoing cancer treatments, who knows what? And so, at their core, their functional capacity may not be 100%. They may be sitting around 65% or something like that. And so, handing them a guideline saying, hey, Hit this, it could potentially be an unrealistic threshold for them. And so it's discouraging. And so we need a better way to dose this. The biggest thing is dosing the appropriate medicine, right? We wouldn't just start someone on a huge dose of medication, we slowly get them there. The same thing with exercise. And so I'm looking at a study today I want to mention. This was not a small study. So, specifically, the links will be in the show notes here or at the end. But this was looking at a systematic review and meta-analysis of 36 randomized controlled trials, and they pooled over 2,500 patients. And of course, by meta-analysis, what I mean is they took all the trials and pulled their data together to see if we can have a bigger sample size to really compare trends. And so, Who was in the study? Well, these adults 18 or older with documented chronic illnesses by some sort of ICD-11 code. A few examples of conditions included were cardiovascular disease, stroke, diabetes, cancer, autoimmune diseases, lots of different ones. And they also had to have comorbid depression, either mild to moderate, and either diagnosed by a physician or hitting the cutoff on a validated scale, like a pH Q9. So, people with chronic diseases and some sort of depression. And what was the intervention? What it looked like? So, it looks strictly at aerobic exercise specifically. I will mention that physical activity guidelines recommend aerobic. And resistance training, that's very important. I'll put a plug in for that, that it's very important. But this study looks specifically at this: so, walking, jogging, cycling, dance, but no lifting, no mixed interventions. They wanted to isolate the pure effect of cardio, and the interventions in this study had to last. At least four weeks. And then, what did they do? Well, they compared it to passive control. So, meaning usual care, wait lists, or standard patient education. No, specifically, not specifically doing exercise. And what were their outcomes? Well, the primary endpoint was improvement in validated depression scores, and the secondary endpoint was adherence to the study. And so that's the setup there. What did they find? Well, Overall, aerobic exercise beat passive controls. Unshockingly, right? Exercise is good for you. Like, end of story, right? We'll just stop it there. But I do want to talk a little deeper about this. And it was pretty convincing there. So. We're going to look at the figures and some of the stuff from the table to make this a little more journal club, more academic in there. But first, let's look at figure two, which is up on this slide if you're watching the video version. And so, this is a classic forest plot. So, a forest plot, if you think about that vertical line, dropping the straight down there. That is zero. This is the line of no effect, meaning that exercise did absolutely nothing compared to the standard of care. Everything to the left of that favors aerobic exercise, and everything to the right favors the control group. So now, if you look at All these individuals, there's lots of rows, right? These trees, there's 36 different studies, they are making up this entire study. Notice how almost every single one of them Is sitting clearly on the left side of that zero line. So that is a visual indicator that exercise is working across the board. But the main event and the biggest thing we kind of focus on in a meta-analysis is the diamond at the very bottom. So if you look here specifically, You see the diamond on the way bottom right there. That is the forest, right? So that's all pooled together. You know, we have the trees and the forest. That's the forest plot. And combined results of all the 2,500 patients. We're looking at that. And the diamond lands firmly on the left side. And they say, hey, it has a hedges G of 0. 73, so negative 0. 73. And you're like, what does that mean? Let's translate what that means, right? From stats speak into real life. So a hedge's G of negative 0. 73 means the exercise group dropped their depression scores almost by three quarters. Of a standard deviation compared to the folks who did nothing. And so the researchers classified this as a large clinical effect size. And so meaning it's not a rounding error, right? This is a noticeable shift in these patients' daily life. And I also want to mention another number on the chart. So, if you look way in the left corner here, it talks about this kind of I squared down here. So, I squared number. We're going to talk about that. The I squared value, it's sitting at 81%. And so I squared is just a nerdy stats term for how much the results bounce around from study study, how much variance is really there. And 81% means there's a High level of variance, the results were pretty wildly different from each other. And why is this the case? And why am I mentioning it? Well, I think it's important to mention. Things like this. First of all, the real world is complex, right? We're throwing patients with heart failure, multiple sclerosis, diabetes, fibromyalgia, all together in the same statistical bucket. And so a heart failure patient isn't going to respond the same way as someone else does. And so that's why we probably see a lot of heterogeneity. And on top of that, though, it's worth mentioning that they did do some analyses to eliminate the statistical outliers, and the I-squared dropped to 33%, meaning much less variability. And they did still see benefit remains. I think that's worth mentioning. It may make it a little more muddy, but I always like mentioning that the world's not a perfect place. And data's never perfect either, but I wanted to at least mention that. All right, let's flip over to figure three now. But if figure two told us that exercise actually works, figure three answers the million-dollar question: how much do we actually need? So, what we're looking at here is a scatter plot showing the dose response curve. So, let's orient ourselves real quick. On the x-axis, we have our dose, essentially, the weekly volume of aerobic exercise measured in met minutes. So, down here, x-axis, met minutes per week. On the y is our response, is our effect size, right? So our hedge is g, as we mentioned before. And now pay close attention though to that y-axis. The numbers are actually flipped. The bottom is zero, then we have negative one, negative two, negative three going up on the y-axis. And they're doing this because a negative effect size means a drop in depressive symptoms. That's like the goal we're looking for. And they designed the graph so that the moving visually up would actually mean a better clinical outcome. It's just a little easier to read. So I just wanted to mention that. And if you look at the blue trend line as cutting through the middle, notice how it's going from the bottom left to the upper right, kind of sloping up into the right. That is telling us that the more exercise we do, the better we're having in terms of symptoms. And specifically, they found that for every 10 minutes of exercise you add per week, depressive symptoms dropped by 0. 01 standard deviation. So as you add more minutes, you climb higher on that axis. And leading to a stronger effect. And it's a continuous dose-dependent improvement. And now, here's a really important part as well. So, if you look at the horizontal red line on this graph, it's a horizontal red line. What's looking there? That is parked right at an effect size of 0. 5, which is what the researchers called the MID line or the minimally important difference. So, in plain English, the minimally important difference is the exact threshold. Where the patient actually feels a noticeable, meaningful improvement in their daily life. So, following that blue tread line up, you see it crosses the red midline at about 405 metmins per week. And that's less than the physical activity guidelines, right? It's still pretty high, I will give you that, but it's less than what they generally recommend. And this is kind of our magic number. It tells us two things, right, for our clinical practice. First, To get a patient to a place where they noticeably feel better, we are going for this. We do not need to necessarily get up to 450 minutes of minutes per week. So that's one thing. And second, because that blue line is a continuous upward slope, every single minute counts. Even if a patient with Pretty severe debilitating disease, can only get a couple minutes or 200 minutes per week. They're still on that line and they're biologically chipping away at their depression, improving symptoms. And our job is just to help them build the momentum and keep going. So that's what that is. And so I just mentioned these big numbers, right? So 405. I want to break it down though for just a second. So these met minutes I mentioned before, but if you think about doing 30 minutes. Three times per week at a brisk pace. So 30 minutes at brisk walk is three mets. That's 90. So we're getting there. And then times three times per week, that's going to be 270 met minutes. And as I mentioned, as we go up, we are getting an improvement every single met minute we increase. But to hit that minimally important difference is that 405 met minute per week recommendations. And to put in perspective, I wanted at least mentioned that's the equivalent of 135 minutes of moderate activity per week, not 150. So once again, just putting it into different terms that hopefully you can understand. But we are not having to get up to that 450, and anything is going to be better than nothing. On top of that, looking at secondary outcomes, patients in the exercise group had an 18% lower risk of dropping out of the studies compared to control groups. And so As we all know, progress is not linear, right? It's more like the stock market, but moving builds momentum. And it shows that, once again, once you start exercising, it actually you want to exercise more. At least that's what it's indicating here. It's a secondary outcome, so it's not perfect, but. People who exercised had better adherence, which was really cool as well to see. And one other thing I wanted to mention is that we kind of looked and saw it on the force plot, but exercise seems to work for almost every condition. It's one of the few medicines we have I can pretty much prescribe to anybody, and that's awesome. Obviously, as a sports doc, I'm not saying everyone should exercise. Like, there are some conditions. That's beyond the scope of this talk, but I'm saying for most people, exercise is probably going to be okay and gonna be safe and beneficial. But do your due diligence. Obviously, looking, I have other content talking all about that. But for the vast, vast, vast majority of people, exercise is going to be good and beneficial for them. So, maybe you're listening now and say, All right, Jordan, I'm on board, but how do I implement this in clinic? I'm glad you asked. So, first things first, start small and validate, right? So, don't let Perfect be the enemy of good because we know that there's a continuous dose response, any volume of exercise helps, even if it's 100 or 200 minutes per week, they're biologically chipping away at depressive symptoms. So that's where we start. On top of that, kind of have a stepwise approach, right? Use shared decision making, build stepwise approaches using SMART goals. Specifically, patient buy-in is very, very important. Using small bouts of walking or cycling to eventually chase that threshold of 405 metmins per week. So, essentially, what it looks like for a patient is say, hey, where are you at? You ask them blatantly, are you doing anything? If they're saying no, then great. Then you work together to build a goal and motivationally interview to figure: hey, what could you do? What can you do? Well, you know, I've had patients say, Okay, well, I can only. Walk around the mall. That's like what I when I'm there, I like doing it. I don't like walking other than if it's associated with something. Okay, cool. Let's walk briskly in the mall. For five minutes. Can we do that three times this week? Cool. We went from 0 to 15. We know we're getting improvements. And then from there, you start working and you can literally prescribe The next week, we're going to do it for 10 minutes, three times a week. And we're just stepwise, progressively loading them with exercise, just like we would a medication. You start them on low-dose medication. And if we're not at where we need to be our target, then we continue to increase our dose. It's the same thing there. So, the stepwise approach kind of going through there. So, that's generally how I think about patients. If we're just like slowly doing it, set the low baseline, monitor their response, make sure it's okay, and continue to go up from there. I think that'd be a solid approach to have. And so, overall, though, I do want people to focus on the big rocks. So, filling up, you think of that jar analogy, the big rocks come first, right? The sand comes last. Movement is one of these massive rocks. So it's going to be very helpful for so many things, and in this study, specifically for depressive symptoms. And so, the big three takeaways are that aerobic exercise is effective and safe with low dropout rates. It's very, very helpful. And there's no minimum floor for activity. Any movement reduces depressive symptoms. And overall, trying to aim for 405 minutes per week for a meaningful difference. And so. Overall, hopefully you found this helpful. Hopefully, you found this empowering, that we can make a real impact on our patients through not another medication, but through exercise. And exercise can actually be a medicine, which is wonderful. But that's it. If you did find it helpful, it means the world to me if you share with a friend. But that's it for today. So get up your phone, get outside, have a rest of your day. We'll see you next time.
