Exercise Compared to Medications or Therapy for Depression

Can exercise truly rival medications and therapy for treating depression? In this episode, Dr. David Puder, Dr. Nicholas Fabiano, and Dr. Brendon Stubbs dive deep into the science of physical activity as a treatment for mental health. Discover the unique antidepressant mechanisms of exercise, how it compares to traditional treatments, and practical tips for prescribing it to patients. Learn about the optimal types, doses, and benefits of exercise, including its impact on mood, resilience, and cognitive health. By listening to this episode, you can earn 1.75 Psychiatry CME Credits. https://www.psychiatrypodcast.com/cme-program Link to blog. https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-230-exercise-vs-medications-therapy-depression-treatment Link to YouTube video. https://youtu.be/AC3P-SrTj1M

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:13David Puder?

  All right, welcome back to the podcast. I am joined today with resident psychiatrist Nicholas Fabiano. He is out in Canada and has written extensively on mental health and exercise. And we have become friends. We co-authored a patient recently and on exercise and depression. And also with us today is Brendon Stubbs, PhD. He is one of the most prolific authors that I know, and one of the top 1% of prolific authors out there. He is approaching this

• 0:53David Puder?

  as a true exercise scientist who has not only written the papers that are the ones that I've nerded out on in the past and previous episodes, but also really changed the face of mental health and seen exercise as something that is a real treatment that is necessary and something that we can get behind. So, welcome to the podcast.

• 1:19Speaker 01

  Thank you for having us.

• 1:21David Puder?

  All right, Nicholas, maybe we should start out with like, why exercise?

• 1:27Speaker 01

  That's a good, good question. A lot of people ask that and kind of how that fits into the whole lens of, of mental health and depression particularly. So, first, I think it's important to define the terms of exercise and physical activity. So, when we use the term "physical activity," that just refers to any movement that uses energy, whereas exercise is more of that planned and structured form, and it's aimed at improving fitness. And where that ties into mental health is that we know that oftentimes we put mental health and physical health into two different bins, but that's not really fair to do because we know how much they overlap. So, exercise has this unique ability to bolster both the physical and mental health of an individual. And there's a lot of different mechanisms in terms of how people think that works.

• 2:10Speaker 01

  And that's a whole different discussion in itself. But one of the interesting ones that we like to talk about is when we look at muscles and their contractions, they can release things called myokines, which is a combination of cytokines and peptides. And that mediates communication with other organs and can increase something called the brain-derived neurotrophic factor or BDNF. And we think that that's has a large effect on the antidepressant effects of exercise as well as other neurotransmitters such as serotonin, norepinephrine and dopamine. But because of all of that, there's really a benefit for the both antidepressant effects. But at the same time, there's a whole lot of potential to maximize one's physical health. So

• 2:50Speaker 01

  it's because of that, it's been first line therapy across guidelines around the world even. And in Canada with our CANMAT guidelines, we see it as a first line therapy. But unfortunately, there's not a whole lot of guidance in terms of how to prescribe it and different things like that, which is why I think it's such an interesting topic to discuss today.

• 3:08David Puder?

  And it it hasn't always been first line therapy.

• 3:12Speaker 01

  Hmm. And that's the other thing too. Like if you looked at it and Brendan can probably speak to this as well too, like years and years ago, and he's a big force and why it's moved forward so much is people probably would have looked at you like you're crazy if you were to say, I'm going to try and treat depression with exercise. But over those last few years, we've seen more and more papers come out, more and more different studies, really strengthening the evidence base for for exercise and treating depression, which is really important from from that side of things. But that kind of comes to one of the things that we spoke about before as well to where we actually wrote a paper on this together about the public perception of exercise and how that's been misconstrued, unfortunately, a little bit recently where

• 3:56Speaker 01

  we know from existing meta-analyses, which is when you bring studies together, that there's comparable effects between things like exercise, antidepressants and therapy.

• 4:08Speaker 01

  But in recent media claims, and this is something that we will speak about more throughout the podcast, this was kind of exaggerated to the stance where exercise was deemed to be 1.5 times as effective compared to these other modalities, which just isn't true. And it's important that we communicate an accurate message to the public. So even though that their efficacy in treating depression is very similar, it's important that we are honest and truthful about what to expect from it, from the antidepressant effects, and also the benefits, as I mentioned before, from a physical health perspective. So although before, exercise wasn't really used as a primary modality for depression, I think with the evidence that's coming out more and more, we're not only getting more evidence

• 4:53Speaker 01

  to support it as a treatment, but also how to use it as a treatment for clinicians.

• 5:00Speaker 02

  Yeah, some great point there, and I'll just pick up on a few points just to reinforce what Nick shared. And I think back to when I first came onto a psychiatric ward in 2003, and most of the psychiatrists, the consultants, or the other people, I'd say, hey, I'm a newly qualified physio, I'd like to get people moving. And they're like, what if we've got a physiotherapist here who's going to get people moving, engaging exercise, and wants to get people to do really innovative things, like get people off the ward, get fresh air, that was not associated with having a cigarette. And people are like, what are you doing here? Why would we want a physiotherapist in a psychiatric hospital? And we got people moving, and surprisingly, people started to feel better as we started to get people's bodies moving, get people

• 5:43Speaker 02

  fresh air and stuff. And I often remind that just how dismissive people were in the clinical realm of getting people moving, and then how, you know, a few years later, a few of us tried to arrange like a national conference with quite a reasonable budget, I think in

• 6:00Speaker 02

  Um. Around physical activity and mental health and we couldn't scrape together thirty people um to come to like consider this topic. The evidence is really not very good and and uh at that particular time, whereas now, just as Nick really eloquently outlines, as we've got lots of evidence, which is fantastic and lots of people want to hear about this and lots of one of people want to consider about the role of physical activity and exercise. So we've made huge, huge strides, which I think is really incumbent upon us as researchers and also people communicating with such, that we need to do this in a really diligent way, in a careful way, as Nick outlined, because this recent piece, which got a lot of media attention, but for the wrong reasons, and people start to become quite skeptical within mental health treatment circles, also patients and other people. And I've had people come

• 6:45Speaker 02

  up to me and say, hey, should I stop taking my medication, stop doing my therapy? And that's not what this research came, which Nick just mentioned, that it's one point five times better than medication. And that's not what the authors found in that paper, and it's not what the evidence says when you look at that paper and what they reported, or you look at direct or indirect trials as well. So as we're becoming more, you know, more more seen within the field and mental health treatment, we really need to be careful, I think, and be stick within what the actual research says, particularly when we're communicating to to to people and we're really talking about the the end of the spectrum where people have mental illness.

• 7:22David Puder?

  Yeah, it's interesting. Um, you know, it's a seductive headline, right? Oh, exercise, one, one and a half times better than therapy, one and a half times better than uh medications. But, you know, okay, what is the control of medications versus what is the control of exercise? What is, what are the types of patients that we're talking about? Are we talking about mild, moderate, or severely depressed people? How have you seen these things weigh into that line of one point five times better?

• 7:59Speaker 01

  Yeah, so I think those are two great points that you bring up. So first with regards to, I think with the meta-analysis itself that made that claim, some of these claims were based on systematic reviews that were of poor, like, poor quality compared to more of the higher quality evidence. So that factors into some of the effect sizes that you see that are reported. And, and leading into that conversation, in exercise research, one of the hardest things to do is the blinding piece, which affects the "quality" of studies that are included in some of these meta-analyses as well, too. So you can imagine for a medication trial, where you have a randomized controlled trial, you're giving someone an antidepressant and you're giving someone a placebo.

• 8:43Speaker 01

  With that, it's a lot easier to blind the participant to what they're receiving. So sometimes in exercise research, you're not able to do that same level of blinding, which adds that level of bias occasionally to these trials as well, too, where you have expectancy effects. You have people that know what group they're in and what they're receiving and, and hope to have positive outcomes from that. And certainly that can play into some of the, the factors that we see. And it's important that we acknowledge it, but it doesn't fully take away from the validity of the research that there is. But again, it's very important that with science, you're transparent and you're acknowledging some of those limitations when especially you're making some of those comparisons. And then the other point that you made with regards to the

• 9:25Speaker 01

  severity of depression, mostly all of these studies are based in the mild to moderate depression, not the severe. And to kind of clarify what that means is mild and moderate, people are usually able to still function. They can still kind of go about their day. They have those symptoms of depression. It's very hard. It's a large burden to them. But it's not to the case where they're severe, bed bound, not eating, not drinking. And it's very important that we make that distinction because I think exercise sometimes becomes a very polarizing topic as a treatment option for some people because they see it as something that can almost be gaslighting sometimes, where you tell a patient to exercise, but they're not able to. And they feel that you, as a provider,

• 10:09Speaker 01

  Are putting them in this situation where you're either pointing a finger at them, saying that you caused your depression because you're not exercising, or you're offering them a treatment that they're not able to do, both of which doesn't feel good for that patient and ultimately fractures that relationship with the provider and perhaps any other experience they'd want to have to do with exercise in the future. So I think that's a very important point to to really consider as well, too. Just because you don't want to be forcing this to your patient and you want it to be something that is feasible and appropriately offered to them, too. Otherwise, you end up with this dynamic where you're kind of inappropriately offering a treatment that maybe isn't right for the for the time.

• 10:53David Puder?

  Yeah. Anything to add there, Brendan?

• 10:56Speaker 02

  I think the complexity, I would say, of all of the papers that were included in this previous piece was it was basically everything that had ever been done on exercise and depression, including people with HIV, with chronic pain, with also arthritis. It's just a really complex, messy picture. So to come out with statements based on that, which is basically, I've used this analogy before. You know, in meta-analysis, when we're pooling studies together with individual meta-analysis, we try and not compare apples and oranges and we try to have as similar studies as possible. But what they authors did, and it was it was a strength, but also a limitation, is they basically included exercise and physical activity in all populations together. But didn't make direct comparisons.

• 11:38Speaker 02

  And that makes it very difficult to come out with statements around the totality evidence, including the previous pieces earlier. But then to sort of compare compare all of these, you know, really heterogeneous populations, putting aside the depressive symptomology and depression as a diagnosis, we know how heterogeneous that is as well, to go and say, we're comparing this to medication trials where you have a much more homogeneous trial design and you can factor in blinding. It's just really unfair. And it's really unfair on on exercise and conversations that we may have with people. And it's just an unhelpful message. I can see that it's a seductive and a clickbait message, but it's not a true representation of of what was found in that research paper and and also the realities of the of the evidence base.

• 12:22Speaker 02

  And it's then it's setting people up to have a hard and a difficult time.

• 12:27David Puder?

  Yeah. And so I think about also the complexity of each individual patient. So it's like transferring research of, okay, like, yeah, exercise is important. It can be like a medication. I'm thinking about one patient who, as a kid, her dad drug her out to do exercise. And so when I start to talk to her about exercise, guess what she starts thinking about? Oh, Dr. Peter's being like my dad. He's being kind of a, he's, he's telling me to do something. He's, and, and there's all of this jarring memories now attached to me talking to her about exercise. And so I think we get, we got a little bit of this when we posted our recent article,

• 13:12David Puder?

  Nicholas, about, you know, how physicians should talk to, should prescribe exercise. And a lot of people didn't even like the idea of saying it's a prescription. It's like, one person was like, how, how dare you say it's a prescription? You know, a prescription is something you passively take. You can't call exercise a prescription. And then I was like, no, here's the script of me writing, you should exercise. And that made them even probably more upset. You know, Twitter, X, it's, it's, it's reduced to like little soundbites. It's like, I can't have a full conversation, which is why I love podcasts, right? And most of the people didn't even read the article. They're just like, I don't like the idea of that.

• 13:56Speaker 01

  But no, I think it's, it's a great point you bring up because sometimes I think from where we're seated, we see this idea and we see that it may not come across like offensive or, or any way, but it's really not until it reaches the public or the patients or potential patient that you really see, you know, most of it was a lot of support and people being on the bandwagon saying like, this is a great idea. But I think it is also equally important to kind of recognize the people that are saying, hey, this seems like condescending or this seems like not right. And, and hearing them out and seeing where we can

• 14:36Speaker 01

  Find that middle ground because I think at the end of the day, you'll never find the perfect thing where everyone's happy with the thing with with a certain prescription or how you deem it. But I think that's where the personalized approach comes to. So I think it's an ongoing process. It's totally okay to release guidelines or a how to sort of thing, but making sure that clinicians aren't applying that like across the board to every single patient. And listening to kind of the people that are upset sometimes and and hearing them out on that side.

• 15:05Speaker 02

  Yeah, and I think there's there's there's just a couple of points I'd like to pick up on there just to sort of feed it feed into this. But generally speaking, I get some pushback from, you know, quite a large proportion of people because I'm also involved in quite a people who quite a few people who are very active and interested in sport and exercise and have high levels of mental health, comorbidity and depression as well. They're always like, well, I exercise loads and I have quite substantial depression symptomology and that's clearly quite a very difficult or even offensive message for people to take. You know, you look at athletes, you know, competing or not competing and you see the high level of symptomology. I know it's a different group altogether, but that's often a pushback I get with people. And the other aspect, maybe we'll come back to this later and we talk about specifics is when we talk about a prescription, if we go back to the medication analogy, if we do a trial or we're

• 15:50Speaker 02

  we're prescribing this and I'm not prescribing to the nation, but on the ward you can say, hey, here's your dose. Take this in the morning and the afternoon. Here's a very accurate measure of your your tablet and we can be very we can be quite confident that someone is taking this dose, assuming they take the tablet, et cetera. But even in the context of trials of physical activity and exercise and depression, it's difficult to accurately quantify how hard and how much someone is specifically doing. So when we come up with specific recommendations at the other end and having been involved in many trials and delivery of exercise, even in like a group setting or an individual setting, it's difficult to know what people have done. So when we make recommendations at the other end of this based on those trials and knowing how inaccurate it could be.

• 16:32Speaker 02

  And it's it's it's it's a difficult, it's slightly lost in translation when we've got this very accurate and clearly defined medication dose or prescription, for instance, but then we talk about exercise. We've got these good recommendations, but I know the reality of the exercise studies is we don't put trackers on people and know how many sets or reps or minutes or intensities people are doing. So there is a slight loss in translation around how good is the evidence that we're coming out at the end, but maybe we'll come back on to that later and we talk about what is the ideal dose or is there such thing as an ideal dose for people too?

• 17:05David Puder?

  Yeah, okay. I want to say one more thing before we move on about the study about like comparing therapy to exercise and medications to exercise. I think one of the big problems with comparing therapy to exercise, a lot of therapy trials are like 12 weeks. So if you look at the effect size of those studies, it's actually, you know, 0.5, 0.6 maybe. Whereas if you take it out 50 sessions, the effect size goes way, way up. And so it's actually very therapeutic. You know, something like after 50 sessions, 75% of people will go into remission. The other, my other point is the nuance of medications. When you look at the increased severity of the HAMD,

• 17:50David Puder?

  it's a measurement of depression. As you get into the higher levels of HAMD, medication, the effect size actually goes up considerably. And so this, this is stuff like, that gets lost in the nuance of a general statement. And there's also just like, when I see a statement like that, just as someone in the trenches, seeing patients for the last, more than a decade, it's like how a lot of people are just not ready. You know, they're just, they're not willing to do it. They don't want to do it. They're too depressed to do it. You pull up their health app on their iPhone and they have less than 1,000 steps a day.

• 18:31David Puder?

  These are people who are not moving a lot, you know, depressed people, people who are going through a lot. The other thing is like, a lot of them have like fibromyalgia or like other body pains. And so, you know, they have reasons why they can't, can't necessarily do it. I had one person in particular, used to be football player, CrossFitter. His right leg swells up, double the size whenever he gets stressed and he has a lot of trauma. And so, you know, we have to think outside the box for different people. And so I think sometimes we lose some of that nuance. But I, but I think it's good to go through the data and to really pull it out and get into

• 19:14David Puder?

  the weeds a little bit, because I think that there is something for a lot of people. And I think as, you know, if you're listening to this, you're a mental health clinician, someone who sees patients, you know, just like we spend hours talking about lithium, we need to spend hours talking about exercise, you know, and we need to really get in the weeds. And actually, I want to just compliment Nicholas Fabiano, Brendon Stubbs, who's, you know, are going to be writing up a lot of these details on my website. I'm going to be part of that. And it's already 19 pages. I think it'll probably grow. But we wanted to put out like something that you can tangibly come back to and look

• 19:57David Puder?

  at each individual study and kind of dig into. So let's, from there, go into what does the evidence actually show?

• 20:06Speaker 01

  So for the overview here, just to give kind of a gross summary before we get into each individual study, what we're going to try to do is speak about a lot of the higher level evidence. And by that, I mean, a lot of the meta-analyses, putting the studies together. But I also think there's value to look at several different meta-analyses and different methods for doing that, because you'll see as we go through it, some of the results, even though there's similar studies overlapping in here, can change how effect sizes are and different things of that sort. So an important thing to be aware of as a clinician, as a medical student, as a resident, that even when these studies are grouped together, you can see kind of different trends when there's different inclusion criterias or different, different things.

• 20:49Speaker 01

  And I think the nuances are quite important, because it tells you a little bit of data for each point. So the first study we'll talk about is a meta-analysis of exercise for depression by Hassel et al. And I believe Brendan was on this study as well, too. This is a meta-analysis that was putting studies together to determine the efficacy of exercise and depressive symptoms compared to non-active control groups. And also wanted to determine the moderating effects of exercise while controlling for something called publication bias, which is where sometimes you see studies with more positive findings or stuff that are more prevalent in the literature. So to do this, they put together RCTs, or randomized controlled trials, which included people that were 18 or older with a diagnosis of depression, or those with depressive symptoms

• 21:34Speaker 01

  on validated screening measures above a certain threshold, and then investigated the effects of exercise intervention. So that could be aerobic resistance compared to a non-exercising control group. So at any point, feel free to interrupt me, but I'll just kind of go through what the main findings were. And Brendan, at any point, this is your paper, so you can tell me if there's anything different or anything you'd like to add to. But what they found was first, they included 41 studies. So it's a pretty big size meta-analysis that included a total of over 2,000 participants. 21 of those studies included people with depressive symptoms, whereas 20 studies included those with depression.

• 22:15Speaker 01

  The percentage of females ranged from anywhere from 26 to 100% in these studies, and the mean age ranged from about 19 to 88. Now, when we talk about effect size, the overall picture, they found large effects for all exercise interventions. So when they put everything together, specifically with a standardized mean difference of negative 0.946, and sometimes people get confused with these numbers. The SMD is essentially a measure of that change over time. And here, we're looking for negative change because we're wanting to see that reduction in the depressive score. And as a benchmark, usually we say effect size is a point two, so absolute size is something small. Point five would be more of the medium, and point eight would be large.

• 22:59Speaker 01

  So this number being higher than point eight would put it into that large category. Then when they restricted the group to just people with depression, the effect size increased a little bit to almost one, so negative 0.998. And then restricting further to supervised exercise intervention, so having, you know,

• 23:20Speaker 01

  When supporting the exercise intervention, whether that's a coach, kinesiologist, something of that sort, further increase the effect size. So you see that in fact, effect size increasing from all interventions, then people depression, then people in a supervised setting. So you see the benefits that kind of add up there. We see moderate effects in the low risk of bias studies. So the effect size for that was negative 0.67. Now, what does that mean? Low risk of bias, essentially when you do a meta-analysis, you assess the bias potential of each study. And as we mentioned before, exercise interventions are particularly prone to having this bias, largely due to the blinding practices sometimes. So

• 24:04Speaker 01

  in this instance, what they did was they restricted it to those studies that were only low risk of bias, which is representing higher quality of individual RCTs. And yes, we see the effect size drop a little bit, but it's still in the moderate range. And then the other part that's important too, is they also did analysis based on exercise type. So when they look at aerobic exercise, so that's things like running, the standardized mean difference or SMD was was large. So it was negative 1.16. Resistance training as well was in the large category, was slightly lower, but it was negative 1.04. And then, interestingly though, the mixed aerobic and resistance, so that's combining those things together,

• 24:49Speaker 01

  was more near kind of the moderate to small size where it was negative 0.46. So interesting findings and we'll, we'll talk about that a little bit after too. And then just a few other things. So they did another thing called a meta-regression. And you may be wondering what, what is that? It's when you do an analysis to see if there are variables that are moderating the effects or the antidepressant effects of exercise that we're seeing here. Firstly, they found that shorter trials were associated with larger effects. And that might show that perhaps these antidepressant effects are larger at the beginning when you're having more of those depressive symptoms. And then the other part was that higher antidepressant use in the control group was associated with smaller effects, which is the point that

• 25:33Speaker 01

  we spoke about before, where it's important to consider the control group that you you have. And they're not always a one to one comparison. If you have a control group that's on antidepressants versus not, it's important to take into consideration. And I think, not to belabor the point, but I think an interesting metric to mention as well too, is the number needed to treat. So when we speak of number needed to treat, that is effectively how many people do you need to treat to get that benefit? And for exercise in the main analysis, the number needed to treat was two. Now, that's a very impressive number. Usually in psychiatric research or mental health research, you don't see number needed to treat that low. Oftentimes for antidepressants, they fall in the range of six to eight.

• 26:18Speaker 01

  To see something, an intervention such as this with such a good number needed to treat is very promising. And then when they further restricted again to those with just depression, the number needed to treat decreased to 1.9. So a further improvement in the people that are maybe having more of those severe active symptoms. And the conclusion of this study that exercise was effective in treating depression and depressive symptoms and should be offered as a evidence-based treatment option. I'm focusing again on the supervised and group exercise with moderate intensity and aerobic regimens. So, yeah.

• 26:57Speaker 02

  Very comprehensive. I think I'll just add a couple of little points, but eloquently summarize that, Nick. I think it's important to place context on how these interventions are being delivered. So most of these people who are having depressive symptoms or having depression are also having support and help in other areas across both groups. So that evens out across the exercise group and the control group as well. So we're talking about this. So quite often people are having antidepressant medication in both. Both groups also, they're also seeing a psychiatrist or another mental health professional and a psychologist as well. So that, so can we say from across these trials that exercise as a standalone intervention? We're not as confident in that, but can we say as an integrated part within the mental health treatment?

• 27:41Speaker 02

  Is it better outcomes? Absolutely. Nick just summarized that very well. But the the difficult thing from looking at all of these trials, as we and others have done, is it's very difficult to understand in those trials. What is the actual control interventions that are being given across both groups? You know, how much medication are they taking often you get and we control there with metagregation? How many are taking um antidepressant medication? You can try uh uh control for that or analyze the effect of that. Within metagregation, how many people have them therapists? How often are people seeing their psychiatrist? How often are people seeing their psychiatrist? So we don't know. So the independence of exercise as an intervention over and above. These other areas is often unclear and then you put these studies together. So that's an important grounding point for this as well and that's.

• 28:22Speaker 02

  A limitation of looking at original trials is we don't have that routine information, but of course. Because of the nature of the trial design, those effects are even across the intervention and the control group. But it's important when we're making statements around how useful is this as an intervention in its own right is we're still really learning. About this in its own right and probably the only other thing I would say is that. Um the two two additional points to help place this is is is adverse events or things that don't happen are relatively low. From these interventions and that's important that we look at that, but again, it's not routinely recorded as well. Eh as in medication or other trials also. But also the the severity of the illness of people compared to other, you know, drug interventions, for instance, is typically lower.

• 29:07Speaker 02

  And you can clearly see there is a bit of a difference between people with the uh sort of symptoms versus the diagnosis and. Bringing back to David's point earlier is that you see a better response to people with higher depressive symptoms than baseline with antidepressants. Is we see that we see the converse in um exercise trials, which is not surprising. People with higher uh symptoms tend to drop out quicker. So I just think those are important. Um context specific factors where there is a lot of unknowns. Around placing these findings in the literature and also in clinical practice.

• 29:43David Puder?

  I think a couple of things that I sort of jumped out at me, even though we make the comment like higher antidepressant use by the control group is associated with a smaller effect, the beta is very small. And so I don't know if that would be clinically significant with that low of a beta. The other thing is sometimes people who are on more medications are more depressed. And so, you know, it's hard to, in mixed studies like this, like it's hard to really say like, oh, therefore, you know, people, if you're on antidepressants, you're not going to have that big of an effect with exercise. I wouldn't say you could take that at all from this with that beta being so small. It was like negative point zero one three, which is super, super tiny effect

• 30:28David Puder?

  size. So if you're on medication, exercise will probably still help you, right? And then the number needed to treat at two, that's really cool. I mean, that's like a great thing. I think, I think with, you know, medications, it's a little bit different because the control is different. And, you know, there's so much in just seeing a psychiatrist and having them talk to you that improves. And, and the placebo effect, right? Taking a pill and you believe that you're taking something that's going to help you, that actually has an impact on your brain in a positive way. So I wouldn't compare apples to oranges with like medications versus exercise, but I would still be excited about exercise. I mean, this is why I talk about exercise all the time on this podcast, like,

• 31:12David Puder?

  and I get excited when clinicians reach out and like, I started exercising two years ago and I'm, it's helped me so much. And I've heard that over and over again. So, okay, those are my thoughts on this study. But very impressive study, Brendan. I'm like, I'm so happy that you were a part of this and you're here with me now. And that's awesome.

• 31:33Speaker 02

  Thank you.

• 31:34David Puder?

  All right, so here we are. Shall we go on to this next study?

• 31:38Speaker 01

  Yeah, sure. So the next study, it's a similar design. It's a meta-analysis, but this one, it's a network meta-analysis, and it's an important distinction. Because of network meta-analysis, whereas the previous study, we discussed group studies together. RCTs looking at the same outcome sort of thing. A network meta-analysis allows for a little bit more reach and indirect comparisons as well, too. But they use a very similar design. So this is by Retia Adan. I apologize if I'm butchering anyone's last name. But the goal of this study was to compare the effectiveness of exercise, antidepressants, and their combination for treating depressive symptoms in adults with non-severe depression. So again, that mild to moderate area.

• 32:20Speaker 01

  And they included RCTs that examined the effectiveness of, again, an exercise, antidepressant, or their combination against treatment alone or a control slash placebo in adults. So what they found in this study was 21 different RCTs were included, which included 2,551 participants. Now, we'll jump right into the results of this, and very interestingly, they found no difference in treatment effectiveness among the three interventions. So when you look at exercise versus antidepressants, when you look at the combination versus exercise, or the combination versus antidepressants, we won't need to go through all of the effect sizes because essentially the summary is that

• 33:05Speaker 01

  there was no statistically significant difference. Now, an interesting finding, though, is they also looked at dropout rates for the different groups. And they did find that exercise interventions did have higher dropout rates than the antidepressant interventions with a relative risk of 1.31. But again, another point, it's important to add context to that because despite the greater dropout rates in that exercise group, the proportion of people with adverse events was actually higher in the antidepressant group. So 22% of people in the antidepressant group had adverse events versus 9% in the exercise group. So even though we're seeing higher dropouts, that may represent another factor where

• 33:50Speaker 01

  there's an opportunity for the clinician to really intervene because it's a lot different to get someone to exercise versus prescribing a medication. Because this study showed that even with the side effects that they were experiencing, there was still greater adherence, which I think is a learning point for clinicians to really be aware of. Because if you're just blindly, you know, quote unquote prescribing exercise, there's much more to it than just saying, I think you should go do this and move forward with exercise. There does need to be guidance, there does need to be monitoring, similar to a medication, to ensure that adherence.

• 34:32Speaker 01

  So again, from this study, the authors concluded that the results suggested no difference between exercise and pharmacological interventions for reducing depressive symptoms in the adults with non-severe depression.

• 34:45Speaker 02

  Great points. I'll just pick up on one really important point which Nick mentioned there is how not to prescribe exercise, physical activity, and depression with some historical context. So a low point of the acceptance of physical activity and exercise was around the time of the release of an old Cockrain review in about 2012. And there was a study done in the BMJ, a primary trial, where they, which was published within six months. And this trial, what they did in this essence was in primary care for people with depression is they went to go see their GP and if they had depression, is they're essentially told through very brief physical activity counselling that physical activity will be good for you and it's a recommendation that you go and do some physical activity, here's what we

• 35:28Speaker 02

  recommend for you, go and do 30 minutes a few times a week, this will be good for your mental health, come back and we'll have a chat about it. That is how not to prescribe physical activity for people with depression, just saying, you know, essentially it's good for you, go away and go do it, see you in a few weeks. And then surprisingly they found another effect, that was a trial in the BMJ in 2013. And around the same time, a Cockrain review was done where they included exercise versus other exercise interventions, pulled them together and showed there was no difference and it came. Out in major headlines that exercise was not effective and there was a big backlash. And that's a bit of historical context that we had to fight, well, not fight against, but really bring the science in a robust way to compare exercise versus non-active interventions to really get exercise back as a viable treatment because it was really dismissed

• 36:12Speaker 02

  for many years after that, after this period historically. And also saying how important it is to do the points around prescription, which Nick mentioned.

• 36:23David Puder?

  That's a, that's a great point. I think just in my own practice, I, I remember reading the book Spark. I don't know if you remember that one, just about mostly cardio and the benefits of depression. I was an enthusiastic first, you know, I guess I was a second year resident and I would talk to people about exercise and they would come back and I would ask them and they would look at me with shame and be like, no, I didn't do anything. And I think, I think this is why maybe cardiologists and most doctors don't, they stop recommending it almost, you know, because it's like, becomes like difficult.

• 37:04David Puder?

  And so I think that's where it can take some like nuance and how to talk to people about it and how to like, you know, put it out there in a way that's like, hey, this is a, this is a positive for you rather than this is like a burden. And, you know, for, for like one person that comes to my mind, it was like, well, what did you used to enjoy in the, in the past, you know, exercise wise? And like, well, you know, in high school I played this sport and I really enjoyed it. But then when I came to college, I stopped playing and I got really depressed. It's like, oh, so you're telling me you started, you got depressed the month after you stopped exercising altogether? Yeah, that's right. Oh, and you used to enjoy that exercise, huh? What do you think about that?

• 37:48David Puder?

  It's like, oh, yeah, I never thought about that time course and how that time really lined up. Yeah, that does make a lot of sense. So, yeah, it's, it's, this is a good study. Exercise and an early study on, out of Duke where they actually did cardio in a group and they compared it to Zoloft and.

• 38:10David Puder?

  They were equivalent in the initial study for mild to moderate depression, but they were in a group and they had people exercising with them and they had a coach, you know, moving them on. So those things can be important and that's part of what I do as well is sometimes I'll try to get the right personal trainer or the right, you know, YMCA class to try to inspire them to have a group to be a part of.

• 38:36Speaker 02

  So important. You just spoke, David, about all of the sort of key ingredients in terms of, in terms of what I talk to patients or people who are struggling is getting back to finding a physical activity or an exercise that you enjoy, removing barriers, because a lot of people I've spoke to have had really not very, some negative experiences around exercise, particularly at school, not felt very good at a particular sport and thought, it's not for me and carried on for a long period of time. So finding something people enjoy and that element of social support we see in this field is just so integral to keep people going and feeling a sense of community and to also have, you know, favorable outcomes too. And you go around any exercise group facility and you

• 39:19Speaker 02

  just see what happened in 5,000 people. So those are some really important points that I consider when I'm working with patients around getting people involved.

• 39:28Speaker 01

  Yeah, and I think to build on that too, as we go through and discuss these different studies and, you know, what works best based on exercise modality or dose, it's important to consider what Brendan mentioned that for, the most important thing is adherence and the best predictor for adherence is working with your patient to do something that they enjoy, because it's the same thing for like a diet or something. If you want to make a change, but if you change to something that you don't like, or it's not feasible for you for, for any reason, it's going to be infinitely harder to stick with that. And maybe you stay with it for a month, but it requires such active.

• 40:08Speaker 01

  Commitment that is not sustainable, maybe sometimes. So the importance is despite the nuances and the importance of the stuff that we're speaking about from these studies, it's important to just, the best thing is adherence. So you want to have the patient in front of you on board with the plan and not forcing them to do something that they're not going to like, and then they're not going to continue to do. Because as you mentioned before too, like, the individual who stopped doing exercise then had more depressive symptoms, you'll be in that situation where maybe they get better, they've been exercising, and then fall off the train of thought and stuff just goes back to square one. So just highlighting the importance of speaking with your patient to make a plan that makes sense for them.

• 40:50David Puder?

  Cool. Okay, let's keep moving. We got a lot of cover here. Let's do this network meta-analysis.

• 40:57Speaker 01

  Yes.

• 40:58David Puder?

  Good.

• 40:59Speaker 01

  So this one is, it's another network meta-analysis. This one is very recent. It's from Notell and colleagues from just 2024. This was published in the BMJ. Again, similar design where it's a network meta-analysis, so you can make indirect comparison, which allows you to include sometimes a broader amount of studies. Again, with the limitation that sometimes indirect comparisons are being made through like these complex statistics. So their goal was to identify the optimal dose and modality of exercise for treating depression, and then comparing it with things like psychotherapy, antidepressants, and control conditions. And they included any RCTs with exercise arms for patients meeting clinical cutoffs for depression. So this study, they ended up including 218 different

• 41:43Speaker 01

  RCTs. So that's a very large amount of studies. That included over 14,000 people. Then when they looked at the effect sizes, they found large reductions for depression. And what I'm going to do first is go by different exercise types. So interestingly, they found a very large effect size for dance. And that's not something we spoke about before. But the one caveat I'll say for this is For this measure that they have, there's not a large amount of studies or participants that went into this effect size. So to take that with a grain of salt as well, too. So this one had about 107 people in this data point, whereas the other ones we're going to discuss have on the thousands or hundreds. So it's important to take that into consideration.

• 42:29Speaker 01

  So the effect size for this was negative 0.96. This effect size is called a hedges G. And without getting too complex into the statistics, it's very similar to the SMD that we spoke about before, where 0.2 would be small, 0.5 would be moderate, and 0.8 would be a larger effect size. So that was dance. And then moderate reductions in depression were found for things like walking or jogging, yoga, strength training, mixed aerobic exercises, and then Tai Chi. And then they also found moderate but clinically meaningful effects when exercise was combined with SSRIs, so antidepressants, or when aerobic exercise

• 43:11Speaker 01

  was combined with psychotherapy. So when it was combined with SSRIs, the effect size was negative 0.55. When it was combined with psychotherapy, it was very similar, so negative 0.54. And overall, all of these treatments were significantly stronger than the clinically important difference compared to an active control. Now, for acceptability, and that means how well did people tolerate this? Like, were people dropping out of this? They actually found that the acceptability was higher, or the odds of dropping out was lower for strength training, so an odds ratio of 0.55, and yoga. Then, when they looked

• 43:53Speaker 01

  at just cognitive behavioral therapy alone, the effects were moderate and small for SSRIs compared to active controls. Then, I think an interesting point to mention is, when you look at all the modalities together, and you do a dose-response curve, For intensity and what that means is looking at the exercise dose measured by the intensity of it and the outcome, meaning the change in depression score, there was a association for increased intensity, leading to greater antidepressant effects. So I think that's an important distinction and something to discuss when you're speaking to patients about what to expect from exercise. And then when they looked at moderating variables

• 44:36Speaker 01

  in terms of what different factors affected the antidepressant effects, they found that the use of group exercise appeared to moderate the effects and the overall effects were similar for individual and group exercise. But there's nuances to this. And I think this is the value of having such a large study with different things overall, where they found that things like yoga is better delivered in groups. And it's kind of what we mentioned before about that social setting. And oftentimes yoga is structured in that way. But things like strength training and mixed aerobic exercise, so that's like kind of a mix of aerobic and sometimes resistance, were better delivered individually. And that could be things that you think of, you know, when you go to the gym, oftentimes people go alone to lift weights and stuff like that. And maybe that's a point of mental

• 45:21Speaker 01

  clarity for people, but nonetheless, an interesting point to discuss. With all of that data, the authors concluded that exercise is an effective treatment for depression, with walking, jogging, yoga, and strength training being more effective than other exercises, and to bring back to the point of the dose, particularly when it was intense. So I think that was a very large study, but there's a lot of interesting points to discuss, but not to get too lost in all of the data.

• 45:51Speaker 02

  Great points. Really well summarized, Nick. And I think there's just a couple of things I would pick up on from that fantastic explanation. The things I take away from this excellent paper, if I'm talking to patients or people, is this great news is there's a lot of methodological publication bias factors, which Nick touched upon dance, for instance, being highly suspicious. And there's some great considerations from people on Twitter, Sir Kremu, I'm not sure if I'm pronouncing that right, has looked at this data and raised concerns about publication bias around dance, for instance, some of these other ideas where some have gone with an effect size of 10, for instance, which have gone into meta-analysis and the authors have gone back and corrected it. Putting

• 46:33Speaker 02

  those considerations aside, the good news if I'm talking to patients or people is It doesn't particularly matter what type of exercise you do. They all tend to have a benefit for improving depressive symptoms. If you do like dance and it does appear that it has a positive effect. If you do like walking, fantastic. This is great news. The other thing which reflects my own clinical experience as well is high intense activity is difficult. And our analysis previously looking at this has shown that we have this trade off between more intensity and more drop off. But for those who do remain, there tends to be a greater effect. So that's an important consideration. Because getting someone who's very depressed to sort of go through very intensive workout, that's not going to last.

• 47:17Speaker 02

  But for those who need analysis that do last, they will get better antidepressant effects. So we need to be able to have those conversations to support people. The higher, higher hard intense activity will result inevitably in more dropout. But for those who remain will have better outcomes. But it's much more important to do something at a low intensity than to drop out altogether. So those will be some important considerations. I'll be having conversations with people around the type. Great news, they all seem to have an effect. But the intensity trade off between higher and lower. And it's more important to do something than to do something, you know, high and drop out.

• 47:50David Puder?

  Yeah, I, I think that my takeaways from this study is that

• 47:56David Puder?

  if someone, if a patient comes back, let's say you talked about exercise and they come back and they started walking. It's like, awesome, that's fantastic. Like, good on you, you weren't walking before, now you're walking. Like, how does that feel? Like, how do you feel in your body after that? Like, so, you know, get them to talk about the positives, things about it. It's, it's going to have an impact. You know, we, we shouldn't be overly ambitious for the perfection combination, you know? There, there's some benefit of, of more vigorous exercise. But it, it may be a journey to get there and they may not get there. That's fine. And they may not need that to, to get the effect that they need to get that extra push to get their depression into remission.

• 48:38David Puder?

  And so, yeah, I've become much more practical. And if a patient wants to dance and they haven't danced, I don't try to convince them to do strength training and something that they're going to hate. I'm like, awesome, yeah, get into the dance studio, do that. That's your thing. So, yeah, enthusiastic about it.

• 49:00David Puder?

  I think the combination of things is also a little bit hopeful. You know, like, yeah, I think that's what I see in practice is like combine them together. Sometimes works better. CBT, a lot of CBT studies as part of the behavioral therapy is movement. You know, so when we look back at a lot of the cognitive behavioral therapies that weren't even based on exercise, a lot of movement was part of the behavioral approach. So, all right, let's keep going. This is, let's compare. Keep it going. Comparative trial between antidepressants or running therapy.

• 49:35Speaker 01

  Yeah, so for these studies now, we've done like a nice overview of some of the meta analyses and like the bigger picture sort of thing. But I think there's also value now to look into some of the individual studies or head to head trials, looking at different interventions and the nuances there. Because when you look from the big picture, you lose a lot of the details of the individual trials, which I think there is benefit in discussing. So for this study by Verhov and Adal in 2023, what they did was they wanted to examine the effects of antidepressants versus running therapy on both mental and physical health. So they did a partially randomized patient preference design. And you might be asking like, what, what does that mean?

• 50:17Speaker 01

  Well, how that works essentially, it's not your standard RCT where you kind of randomized people in a blind fashion to each arm of the study. Here, the patient preference part means that they allow, they ask people, will you be willing to be randomized? And some people, are you not willing to be randomized? And the people that are not, they allow them to pick their intervention. So whether that be exercise or antidepressants. And then the remainder, they randomized. So it's an important point to discuss in studies like this. So what they did was they had 141 patients with depression or anxiety disorder with a mean age of 38, 58% being female.

• 51:00Speaker 01

  45 participants received antidepressants, whereas 96 underwent running therapy. And they were randomized or offered the preferred 16 week treatment. So again, the antidepressant medication was either escitalopram or sertraline. And or they were offered a group-based running therapy, which is two times or more per week. They took assessments at baseline, so they call that T zero. And then post-treatment, which is week sixteen, which they deemed to be T sixteen. They included the mental health stuff, so diagnosis and symptom severity score. And also several physical health indicators. So looking at metabolic and immune indicators, so heart rate, weight, lung function, hand grip strength and overall fitness.

• 51:45Speaker 01

  So getting into the results, what they found was that the remission rates at week sixteen were comparable. So the antidepressant groups showed a remission rate of forty four point eight. Whereas the running therapy group had a slightly smaller, but not statistically significant remission rate of forty three point three. Interestingly, though, there was a larger decrease in anxiety symptoms after six weeks in the antidepressant group. Which may suggest a faster improvement on anxiety-related symptoms from medication. Which I think is an interesting point to discuss because oftentimes from the psychiatry lens of things, we tell patients with anxiety disorders that these medications actually take longer to treat things like anxiety compared to depression. So I think it's a point to have a discussion with patients about.

• 52:31Speaker 01

  However, the beyond the mental health side of things, the groups differed significantly on various changes in physical health. So all of these changes that I'm going to describe, they had improvements more so on the exercise arm. So there was improvements in weight with an effect size of zero point five seven. There is an improvement in waist circumference with an effect size of zero point four four. And there's an improvement in both systolic and diastolic blood pressure. Improvements in heart rate and heart rate variability. And then getting into some of the adherence data, in the antidepressant group, eighty two point two percent of the participants adhered to the medication treatment protocol.

• 53:14Speaker 01

  Whereas, as we've kind of discussed before, in the running therapy group, only fifty two point one percent completed over twenty two sessions of the exercise therapy. So from this, you do see that the treatment adherence was actually significantly higher again in the antidepressant group compared to the running therapy group. Which is a point that we discussed before, but it's important to discuss when we're seeing it at the individual study level as well, too. Again, limitations that I mentioned before, though, was that a minority of the participants were willing to be randomized in a true RCT fashion. So that preference does come into play, where people, the running therapy group was larger because of that preference for running. And from this, the authors concluded that while the interventions had comparable

• 53:58Speaker 01

  effects on mental health, running therapy did outperform antidepressants on various of the physical health measures, which is important when you're treating patients, because a lot of the times antidepressants can actually worsen some of those measures that we talked about. So something to have a discussion with your patient in front of you about the duality and the how exercise can really have that holistic picture where you're treating both the mental and physical and not just addressing one. So that's kind of the summary for that study.

• 54:28David Puder?

  Excellent. Brendan, any thoughts off the top of your head on like things you appreciate about this study in particular?

• 54:35Speaker 02

  I think this is a really ambitious study. I think this is a really good study to try and address the question, which we don't always very keen, like clear to nearly answer on, how does exercise compare to antidepressant medication? And I think despite the short term follow up and some of the methodological considerations, I think this is a really important study to guide where exercise, in particular running, can play a role in mental health promotion as a frontline treatment. So I think it's a really nice, novel, important study, and I think much more work should be done to build upon this.

• 55:10David Puder?

  I think that, you know, you said antidepressants usually can take longer with anxiety. At six weeks, usually we see kind of where we're going to be at. And so I think the antidepressant drop in anxiety from, it looks around like 27 with the Beck Depression Inventory down to like a, around an 18 at week six.

• 55:34David Puder?

  That's a significant drop and can take the edge off. So that's an important drop. Running, it seemed to decrease from around 25 to 20 by the end of the study at 16 weeks. So there's a drop as well. But yeah, the antidepressant seems to do a little bit better job specifically on that. But then I'm also aware of, like, we're throwing in people who were fairly noncompliant into that mix as well. Right? And so you have to imagine, if you're a patient listening to this and you're like, okay, what should I do? Yeah, if your compliance is higher, probably going to have better effects.

• 56:17David Puder?

  And, you know, I was looking at like the treatment for the running was two or more times per week. And so to have 50 people not do two or more times a week is significant. 50% of the time, they're not doing two or more times a week. So they're doing like one time a week or zero times a week sometimes. Nicholas, any thoughts on like the level of noncompliance?

• 56:39Speaker 01

  No, I think it's an important thing to discuss when we look at these kind of analysis. And I think that's why sometimes studies take that intention to treat analysis where they keep people where they're randomized to and look at it for more of kind of that real world setting. Because I think even though it kind of clouds the data from that side of things, it also can provide you with more of that kind of realistic picture of the patient, maybe not the individual patient in front of you, but the larger group of patients that you may be seeing. And perhaps, not that you expect noncompliance, but that it wouldn't be maybe perfect at the beginning. And to set those expectations, because I do agree that if you have an intervention group for exercise, where there's a large amount of people that aren't actually adhering to the intervention,

• 57:24Speaker 01

  of course, you won't see kind of the effects that you would hope to or expected to see. But at the same time, I think it kind of goes back to the point where it's so important and it's an important point to discuss with your patients too about, you know, even in the studies, we see people that are not adhering when they have more supports and stuff in a real world setting. So to not discourage people and say, hey, this might be hard, especially if you're just starting running. It is not something you've done before. But goes to show that even if you're not fully adhering to it, that you're still seeing the benefits to that are comparable to the antidepressants, which I think is a promising sign. And sure, if you had perfect adherence in both arms, maybe there would be a leg up in the running side of things. But I think even without the perfect adherence, it's still a very, very promising thing.

• 58:11David Puder?

  Nice. Okay, let's keep going. Internet-based cognitive behavioral therapy compared to exercise.

• 58:17Speaker 01

  Yeah, so we're almost there. I think two more RCTs and then we'll get into more different content. So for this study, I thought it would be important to kind of discuss CBT more so and comparing it to exercise because before we've been speaking more heavily about medications. So the objective of this RCT was to compare the effectiveness of exercise, internet-based CBT and usual care for depression. So this was a three-group parallel RCT with assessment at three months, so post-treatment, and 12 months, which is their primary endpoint. They included a pretty large sample, so 740 adults with a mean age of 43, 73% being female, with 56 receiving usual care,

• 58:59Speaker 01

  49 receiving exercise, and then 42 receiving CBT. And again, they fell into mild to moderate depression. And they were recruited from a primary healthcare center. So it's important when you kind of apply these findings elsewhere to, to what patient population were they looking at? And again, this is a 12-week intervention. So the difference groups that they were assigned to first was a supervised group exercise. So patient in the exercise group were actually further randomized into three different conditions. So there was a light exercise, which was stuff like yoga or stretching classes. There was moderate exercise, which was like an intermediate aerobics class. Then there was vigorous exercise, which was a higher intensity aerobics

• 59:43Speaker 01

  and body weight strength training class. And participants were requested to complete three 60-minute sessions per week for 12 weeks total. And these sessions typically included five to 20 participants. So important point to mention there, it's in a group too, right? So it's not just the exercise, there's also the social component as well. Then with the internet-based CBT, this involved people working through a self-help manual available in the form of online modules.

• 1:00:13Speaker 01

  I think this is very interesting too, because the the other arm was usual care by a physician. And I think when you hear usual care, you wouldn't expect this to be kind of what it is. But they were followed by their primary care physician. But most instances, usual care also consisted forty five to sixty minutes of CBT, delivered by a psychologist or counselor. So oftentimes, patients, when you hear usual care, you wouldn't actually have the therapy arm put in with that. So I think it's an important point to discuss as well, too. Now, the authors found that the mean difference in the Yamadra score at twelve months was pretty much the same between all of them. You see small differences in the numbers, but the error bars overlap, so it's not statistically significant.

• 1:00:57Speaker 01

  So the CBT or Internet-based CBT decreased by twelve point one. Exercise was eleven point four and usual care was nine point seven. So they found that exercise and ICBT had pretty much equal effects, which was greater than the treatment as as usual. And from that, the authors conclude that the long-term treatment effects reported suggest that prescribed exercise and clinician-supported ICBT should be considered for the treatment of mild to moderate depression in adults.

• 1:01:33Speaker 02

  There's a couple of points I'll pick up on, just to say on that excellent summary. And just a bit of context of this, so some of the criticisms, the fair criticisms of exercise as an intervention for depression have been that the trials have been relatively short-term follow-up, you know, twelve weeks, sixteen weeks. And we don't know if the long-term effects hold. And this is a really nice study that really looks at that long-term follow-up. And that's helpful to address some of those concerns around or or or helpful comments. Do these effects maintain over the long period of time? So it's very helpful for that, for the context. And also, many of the exercise trials are relatively few numbers, so often less than a hundred people.

• 1:02:16Speaker 02

  So this study also does a great job of adding the power, sort of confidence that we have in these findings because of the larger numbers of people. So it really helps to add some credibility points for those two key and important, you know, criticisms or critiques of the exercise intervention literature for depression.

• 1:02:36David Puder?

  One thing to add, if you look at the study, specifically at the mattress score, which is like the severity, most groups start around 20 and most groups end around 10. So you're really getting a halving of the symptomology. So what does this mean in my sort of like real life practice, right? This is a step forward, right? If you can halve someone's symptoms, that's fantastic. As an outpatient provider, you're not done. You're going to continue to work with them. You know, like a couple of months of therapy may not be enough. Couple of months of exercise may not be enough. Like, okay, so now they're doing exercise.

• 1:03:21David Puder?

  They're at half the depression rating, but they're not doing therapy. We may add in the therapy at that point. And, you know, basically try to get them to zero, right? Our goal is complete remission or just absolute thriving in life. So this is just some thoughts there. But the halving is still very significant and it's great. So, yeah, great study.

• 1:03:48Speaker 01

  And I think as you mentioned, like having it can create that momentum to have that change or additional stuff. So whether you started with exercise or whether you started with CBT, maybe you can add the other, maybe you can start both at the same time. But having it can really give someone maybe that additional push or the, maybe their a motivation that they were experiencing from their depression has got to a point where they're able to engage in either the therapy or exercise arm, which I think is really important for a clinician to consider when you have a patient seated in front of you.

• 1:04:20David Puder?

  A hundred percent. And also I tell, you know, I used to run an IOP partial track, backed out of that at this point in my life. A couple of months ago, I stepped out of that role. But in that role, I would tell patients like, hey, the more, you know, if you can exercise... It's going to increase things in your brain which are positive, which is going to maximize the hard work that you're doing in group. You know, you're in group three hours a day, five days a week. You know, and so if you can get the exercise on top of that, it's going to give your brain that good stuff that it needs to make those changes, to make the the new links and stuff like that. So, um, so, yeah, I'm not, I'm not surprised that it's only a half decrease. I think that's excellent.

• 1:05:03David Puder?

  And I think from what I expressed before, like psychotherapy studies, it's a dose response. So it's, it's not going to be, you know, 10 episodes like an insurance company will pay for to make someone better. It's going to be 50, 100 sessions, you know? Like, that's probably what's going to get someone to a better place. And if they have a lot of issues and personality issues, it's maybe it's going to be more. Right? And so, okay. Let's see, what's the next study here that we have?

• 1:05:34Speaker 01

  This one's pretty similar. I can give, um, the one interesting point of it, rather than going through it again and going through another RCT of it.

• 1:05:43Speaker 01

  If that's okay.

• 1:05:43David Puder?

  Yeah, just give, give the, the highlight of your takeaway and then people can read more if they want on the website.

• 1:05:49Speaker 01

  Yeah, so this one is, again, it's another study looking at exercise plus medications and CBT. This one was interesting because they showed very similar findings to, as we discussed before, about the benefits and reduction in depressive symptoms. But the other thing that I, I found interesting was they actually took blood levels in the study as well, too. So it goes to the point that you spoke about speaking to patients about changing levels in your brain with exercise and everything of that sort, where the exercise group had a significant increase in BDNF, which is what we discussed before, the brain-derived neurotrophic factor,

• 1:06:23Speaker 01

  which I think is important. And that mediated both improvements in depression score and in sleep quality. So that BDNF not only increases, but we see associations with things that you see in depression. So the depressive symptoms, but also sleep quality is something that's heavily impaired in, in someone with depression. So you see these actual blood-based markers having differences, which I think is, is important. And again, conclusion was the same as we've kind of discussed for some of the other ones. But I think it's an interesting point to, when, when the patient can see that there is a change physically because of that exercise, and it's associated with some of the symptoms that they're experiencing.

• 1:07:01David Puder?

  Yeah, that's super interesting.

• 1:07:05David Puder?

  It seems from this study that you could say exercise was better at antidepressants

• 1:07:12David Puder?

  at increasing brain derived autophoric factor. Is that, is that what you're saying? Or is it the exercise increased in?

• 1:07:19Speaker 01

  Yeah, it seems like from what the study concluded here, the exercise did have a significant increase relative to the other arms in the study.

• 1:07:28David Puder?

  So was the exercise added on to antidepressant medication and cognitive? And in a second group, the exercise was added on to cognitive behavioral therapy.

• 1:07:37Speaker 01

  Yeah, so I think, yeah, there's eight, it was a very small trial, but eight patients that had antidepressants performed an eight week exercise intervention in addition to the cognitive behavioral group therapy. And then eight medicated patients attended only the cognitive behavioral group therapy alone. So there is both of them, the medications and the exercise together compared to the therapy. And the variable that's changing is that, the exercise portion. But nonetheless, I think it's a small sample, but interesting findings from that front.

• 1:08:11David Puder?

  Cool. And so, yeah, exercise add on improves treatment, improves BDNF, which is kind of like what I was saying before, brain derived autophoric factor. Like if we have things in our brain that are healthy, when we're doing the work of psychotherapy, the psychotherapy is going to work better. Especially when we're treating more complicated issues, more severe issues, more protracted issues. I don't see where that isn't the case in all of the data that I've seen. Okay. How about multi-system benefits of exercise? I mean, the, yeah, and this is kind of, this is kind of where I get excited. It's like, we're not just treating depression.

• 1:08:57David Puder?

  We're treating tons of things. I mean, this is where I've like talked about in previous episodes on like mortality reduction, you know, heart disease reduction.

• 1:09:09David Puder?

  It's the most potent thing that I know to decrease dementia risk. Sauna would probably be up there, right next to it. I don't know if you saw my episode on that, but 60% reduction and people were using it four times a week. Incredible. Okay, so yeah, tell me about this. Tell me about your thoughts on this.

• 1:09:33Speaker 01

  Yeah, so I think for this one, we don't necessarily have to get too into the study itself, but I think, like you mentioned, the major benefit of exercise is that multi-system benefit. And the other thing is the bidirectional relationship between depression and some of these physical ailments. So an example would be someone that has a heart attack is at a higher risk of developing a depression. And it goes the other way, too. Someone with depression is at a higher risk of having the heart attack, sort of thing. So that's the case for a lot of different physical health disorders where there's that overlap. So exercise is in this unique position where you can really benefit one's physical and mental health.

• 1:10:17Speaker 01

  And whether the mechanism is mediated through the benefits in the physical health, I think it's besides the point even because you're wanting to treat that patient in front of you, regardless of you're a primary care physician, regardless of you're a psychiatrist. I think it's important that you're treating the whole patient because you want to make sure that you're able to really bolster that. Because as I mentioned, you see so many associations between the two and being able to treat both at the same time is really quite powerful for the patient and it gives them that sense of control as well, too.

• 1:10:52David Puder?

  So good, yeah. And, you know, quality of life, long term, right? Especially us outpatient providers who are seeing these patients over decades. It's like, you know, the ability to holistically reduce burden, the burden of disease in multiple domains. It's like, we know that people with diabetes that are uncontrolled have like much higher rates of mental health issues. We know that people with strokes have much mental, much more mental health issues. We know, you know, all of these diseases increase mental health issues, especially as they get older. And so, yeah, I think it's like.

• 1:11:37David Puder?

  Taking that holistic approach is just satisfying when you see people thriving in their 60s, 70s. Brendan, anything that kind of like, as you have dove into this research, has kind of surprised you?

• 1:11:52Speaker 02

  I think the point is a reflection on clinical. Often, we, people, when we're helping people move, is they've often got aches and pains and other physical concerns. So in terms of motivating people to become interested and want to make a behavior change, which by definition involves effort, this is an important hook. When I'm having a conversation with a person in front of me who's concerned about their heart, concerned about their diabetes management, or is in pain, that you have this dual mind-body approach is really helpful when I'm having conversations with people too. But also with reference to other treatment approaches, for instance, we know that while medication is very helpful for people's mental health symptoms and a vital part for people's

• 1:12:33Speaker 02

  recovery, it does have some side effects for many of these systems for people as well. I know there's systems put in place to cover that, but I think that's one of the added benefits of exercise in conjunction with other approaches.

• 1:12:45David Puder?

  Nice. All right, let's talk about antidepressant side effects. I mean, you know, when we think about like, okay, this is kind of like one of those things that I end up treating, right? Long term, someone will come in a severe depression, they get on an antidepressant thing, maybe they get better, but then they have the side effects, right? And you have to deal with those. And I've had this conversation with so many people of like, okay, if you want to have less side effects, we need to do lifestyle things as well, right? We need to get you into therapy, we need to get you exercising. Why don't you take us into this, Nicholas, and kind of, your thoughts?

• 1:13:22Speaker 01

  Yeah, so like, as you mentioned, a big thing with tolerability of any medication, and particularly like psychiatric medications, is what the side effect profile of the medication is. So the expected side effects, and also when they actually occur. So when we look at antidepressants, they are associated with the side effects across a variety of bodily systems. So, you know, cardiovascular, you can see Increases in resting heart rate, decreases in someone's heart rate variability. You could even see increases in blood pressure, particularly when you're using antidepressants that have more of the norephrenephrin component, so SNRIs. You can also see gastrointestinal or GI side effects, so things like constipation.

• 1:14:04Speaker 01

  Metabolically, which is something that is very like a concern for a lot of people is the weight gain perspective as well, too. Sleep, you can also have issues with sleep latency, so how long it takes for someone to get into their REM sleep or insomnia. And then, long term, there are associations with antidepressant use and even increased risk of fractures. So, the interesting point, though, is when you hear that list of side effects that I had described there, when you think of exercise and think some of the studies we've discussed prior to this, there's benefits almost to all of those. So, exercise can help decrease your resting heart rate. It can help increase your heart rate variability, so its ability to adapt to different scenarios.

• 1:14:49Speaker 01

  It can decrease your blood pressure with regards to constipation. Sometimes people just need to get moving to get their bowels moving as well, too. Metabolically, exercise improves, you know, weight, waist circumference. Sleep, if you're exercising more, you can get better sleep at night. And then with increased risk of fractures, like particularly in elderly individuals, when you're looking at things like resistance training, that's one of the best ways to reduce someone's risk of having a fracture, which can have detrimental consequences for them from both a morbidity and mortality perspective. So, again, just to highlight the point we discussed before, where although in a lot of the studies, antidepressants and exercise have very similar effect sizes for the treatment

• 1:15:31Speaker 01

  of depression, it's important to look at the whole picture and the physical health side, too, where there are side effects with antidepressants, there are benefits to exercise. So, something for the clinician to be aware of when either you're choosing either intervention or if you're using both together, that exercise might be helpful in mitigating some of those side effects or reducing it. And having that discussion with the patient, I think, is quite important and being able to allow them to make an informed decision with regards to that.

• 1:16:02David Puder?

  Yeah, and I would just add, you know, we listing off a bunch of side effects from antidepressants. Obviously, you know, if you're on an antidepressant and you're hearing this, you may want to check your specific antidepressant because this is kind of like maybe not applying to all antidepressants, may apply to some, not others. So, so, you know, if any of those words freaked you out, go, you can talk to your doctor. You can get a specific list with your prescribing guide of certain medications and what their risks increase and stuff. But I think that the idea is well put, Nicholas, that a lot of the things that you mentioned, I think specifically that exercise helps. And so just to even decrease the burden of side effects through exercise, I think is

• 1:16:47David Puder?

  potent. Even just walking, think about walking decreases constipation, a lot of these things, you know, like sleep, exercise increases, improves sleep.

• 1:16:59David Puder?

  You know, strength training, best way to strengthen your bones long term. Yeah. Brendan, anything jump out or anything that you've specifically gotten questions about in your career or just kind of like seen?

• 1:17:12Speaker 02

  I think what I've seen this done, done, done well in clinical practice, when clinicians have prescribed medication, I've seen the consideration of the side effects, the ongoing monitoring, and then also the incorporation of lifestyle management alongside that in conjunction with the person. So I think that that's just a really important holistic way to approach support person. If we do know that this medication is going to help improve someone's mental health, but it is associated with increased risk of these factors, then I think it's quite an integral and important aspect that this lifestyle management included there too.

• 1:17:49David Puder?

  Cool. Okay, so let's talk about what is the optimum amount of exercise to improve depressive symptoms? We've touched on this a little bit before, but let's go back through it a little bit.

• 1:17:59Speaker 01

  Yeah, so for this study, again, not to get lost in the the details of it, but I thought it would be an interesting kind of discussion to highlight some main points. And this was by Tian et al. in 2024. So again, a very recent study, which was a systematic review and again, network meta-analysis, which brought together different RCTs to examine the effect of four major types of exercise. So aerobic, resistance, mixed, and mind-body on depression, and to look at that dose-response relationship. So again, they included people 18 and older with a diagnosis of depression.

• 1:18:34Speaker 01

  And they or they had a score above a specific threshold by a validated measure. And what they found was they included 46 studies, so just over 3,000 people. And they found again, just to highlight the main point, that all exercise types did improve depressive symptoms. So aerobic had a SMD of negative 0.93. And here, negative is a good thing. It's it's reducing depressive symptoms. Mind-body was negative 0.81. Mixed was negative 0.77, and resistance was negative 0.76. So they're all clustered very close together. And you'll probably see, if you went through all the studies we discussed, sometimes they flip-flop between one another, where resistance is higher, aerobic is higher. And I think, just to take it with a grain of salt, it really depends on how these studies are put together, how what the inclusion criteria is, and then that really can change the effect size ever so smallly.

• 1:19:27Speaker 01

  But the important part of this is to speak about like the dose. And that's kind of the point of this study, where before we talk about doses, I think it's important to speak about what how you kind of quantify that. And one method that they use in this study was called the MET, or the metabolic equivalent of task. So it's essentially a ratio of the rate at which a person expends energy relative to the mass of that person. And For those that are listening, if you go online, you can see kind of a chart that kind of breaks down some of the different examples of what activity would be at what METS. So like yoga would be something that's 2.5 at the lower end, whereas something like competitive cycling would be at the higher end of 16.

• 1:20:10Speaker 01

  But that concept is just to explain kind of the dose-response relationship. And what they found was they set up a curve between exercise dose in METS and they compared it to their dependent variable, which was the change in their depressive symptoms. And the overall trend was they found a U-shaped association for their overall studies. So I think the important point for clinicians for this is what you see, and if you can't see the graph and you're just listening, just to explain it, you see the slope of that graph is quite steep at the beginning. Now, what that means is that at the lower doses of exercise, the slightly more and more that you do, you see greater benefits, and there's a little bit of a diminishing

• 1:20:54Speaker 01

  return as you do more and more when you're getting to the higher and higher amounts of exercise. So I think that's a very reassuring thing for patients when you have a lot of people that are saying, "Hey, I only have 15 minutes to do something. Like, is that even worth my time to try?" And the answer would be yes, because these small amounts have an incrementally beneficial effect on depressive score. And they also stratified further by different types, as I mentioned. So they looked at aerobic, resistance, and mixed. And we won't get into all the specific charts, because they're quite complicated, different dose-response relationships. But they found different associations depending on the exercise type.

• 1:21:34Speaker 01

  But I think the important part to mention is the minimum effective dose was estimated to be 320 metabolic equivalents minutes per week, and the optimal dose was 860. And for those listening, you might be wondering, like, what does that mean? Like, how am I gonna hit 860? Well, it's actually not that much. So to give some examples of what that would look like in a week, that would be equivalent to 245 minutes of walking, so a walking estimated at 3 minutes. .5 m per minute, that could be 140 minutes of moderate intensity aerobic exercise. So that's estimated at six m per minute or 215 minutes of yoga. So four m per minute and that's in just a week, right?

• 1:22:19Speaker 01

  So that's not like a daily thing. I think when you hear the number eight sixty for the optimal amount, that's like, wow, that sounds like a lot. But when you give those examples of what that actually represents, it's not a whole lot to have that quote unquote optimal amount. And then when you look at the minimum effective dose as well, too, it's half of that. It's it's less than half of that. So when you look at those metrics, I think that should be something that you can really speak to your patients about that. Even if you're able to do a little bit, those benefits keep increasing and to reach the optimal. You know, is a goal that is achievable. It's not something where you have to be some Olympic level athlete or something to have those benefits. But you can really get that momentum going. So from this, the authors concluded that clinicians should carefully select the appropriate dose of exercise

• 1:23:03Speaker 01

  based on their individual characteristics and needs, because as we showed based on the breakdown by type, there's not a huge difference and the adherence really comes from getting that patient invested into something that they enjoy.

• 1:23:16David Puder?

  I I am, I'm not surprised at the U shaped curve. I think this is a great example of why you can't just do a correlation. Correlation is just a linear line, you know? And so looking at this U shaped curve is so helpful because, you know, as because I've seen professional athletes who come and they're not getting an antidepressant effect from exercise. Actually, exercise is it's like draining them. And when you do it at the highest levels, it's it's going to take almost everything from you. You know, think about like people training for like a bodybuilding competition in the last couple of months. As they're cutting, they're absolutely miserable in the midst of doing exercise because they're losing weight and they're starving themselves.

• 1:24:01David Puder?

  And they're, you know, all these other things. So, you know, at the high, whenever you do something at the highest level, you're going to sacrifice something. And so.

• 1:24:11David Puder?

  Yeah, I found that interesting. I also was thinking to myself, okay, how many mets do I expend per week? I don't know if you guys do this calculation for yourself, but I tend to train about two hours of lifting per week and about one and a half hours of total rowing time. And so that ends up being, if you calculate about five mets for both of them, you know, intensity wise, that's about 1,000, 1,050 mets per week, mets per, met minutes per week in that measurement. So yeah, have you guys thought about this for yourself?

• 1:24:47Speaker 01

  Yeah, I haven't done the calculation for myself. Usually what I do is I'm pretty bad with doing the cardio side. I do a lot of resistance. So I probably hit the gym about five times per week for about an hour, hour and a half session. So I'm not sure what mets that works out to, but.

• 1:25:03David Puder?

  Lifting, five, five hours lifting, five times for about.

• 1:25:07Speaker 01

  Yeah, five times.

• 1:25:08David Puder?

  Okay, for about an hour each?

• 1:25:10Speaker 01

  Yeah, about hour each.

• 1:25:12David Puder?

  Okay.

• 1:25:13Speaker 01

  Sometimes I played soccer before.

• 1:25:15David Puder?

  What do you do?

• 1:25:16Speaker 01

  Recently.

• 1:25:17Speaker 02

  I think that goes to the point that the mets is a, is a bit of a confusing measure. And if I go and talk to patients or anyone, just getting the concept of minutes and intensity is quite a complex thing. So talking about mets is really confusing. It's a very sort of specialist sports medicine. So I'm not sure how helpful it is in, in practice when I'm talking to people. I mean, we're all thinking how much, how many mets do we do? And if we look at like guidelines that are recommended for how we do, it all talks about how many minutes do we do and what intensity do we do? So moving mets is confusing people even more away from that and getting really technical. And I think it's just a bit, it's a bit confusing for people when we're talking to, to sort of patients in my experience anyway. And the other sort of thing that I would sort of say on this before I come back to

• 1:25:58Speaker 02

  the findings is that if you put numbers in, in, in, in a paper, you will always get an output, but how good is the data? Getting back to a point I made earlier.

• 1:26:08David Puder?

  Okay.

• 1:26:08Speaker 02

  And knowing the trials and delivering the interventions. Is we're never very sure how many minutes people are doing in certain zones. I mean, when off, very, very rarely do people have, you know, accelerometers on. So they've got very accurate measures for each people put that in. So often this is the here was the intervention. We did three times thirty minutes per week and it was in a group setting. But you know, within a group setting, people work at different intensities. People are stopping and starting. So it's a useful guide. And I think the U shaped curve, for instance, is absolutely uh very, very true. But I'm not quite as confident on some of the numbers per se. And the things that I really took from this is similar to what I mentioned earlier. It's it's reinforcing again, the key point. It doesn't particularly matter about the type.

• 1:26:51Speaker 02

  And that's great news because I guess people can mission to go and find that thing in conversations or individually that you particularly enjoy. But also, again, the point which Nick really mentioned is it doesn't need a lot, particularly if you are, you know, really struggling with depression to get some improvement. And those improvements sort of dissipate the more that you do. And those are sort of real key things for me when I'm talking to people and based on what I, you know, in my experience too.

• 1:27:16David Puder?

  Hmm, okay. So what is your workout routine, Brendan, look like at this point in your life?

• 1:27:23Speaker 02

  I work out five or six days a week. Bit of bit of lifting, a bit of running, maybe running once or twice a week. I try and play badly, a bit of some racket sports, bit of tennis, bit of pedal. And recently a new dad, so I'm picking up and carrying a new baby around quite a bit.

• 1:27:40David Puder?

  Nice.

• 1:27:43David Puder?

  Nice, yeah, I I was jumping on the trampoline this morning with my son. It's it's one of one of his loves. Um, yeah, so I think I think that movement, it's it's interesting how Mets, um, you know, I think with chat G P T, I think it's the easiest way to figure it out. If you just put your workout and just ask it to estimate your Mets. Um, it can do a pretty, or the Mets minutes per per week, you know, can calculate it. But yeah, I agree. It's it's a it's a complicated number. We shouldn't dwell too much on it. But it's interesting. And I think the general takeaway is, you know, half an hour a day, five days a week is probably going to get you there for most people. This isn't a huge, like, you need to be doing this an hour and a half,

• 1:28:27David Puder?

  six days a week type of commitment. This is like, get in, get your workout done. You know, this is what my advice for medical students as well, like, don't give up your workout routine. Get in the gym, do half an hour hard and get out. It's gonna help your brain. And I tell residents that as well, although it's sometimes harder to get the workouts in. Okay, let's talk about the antidepressant mechanisms of exercise.

• 1:28:52Speaker 01

  So yeah, for this one, what I did was I picked a paper that was from 2024 by Hurt et al. It proposed more of a novel mechanism for the antidepressant effects, because I wanted to take a step back first and say, to know the mechanism for the antidepressant effects of exercise suggests that we know the mechanism of depression itself, which we don't yet. Like, we know that there are neurotransmitters implicated. We know that there are deficiencies seen in depression. Now, we don't know if it necessarily causes it. So just taking that step back to say that, you know, there's still that question mark about what's really...

• 1:29:28David Puder?

  Yeah, and I would say, depression itself is like a fever. It's like, do you know what causes the fever? You know, like, all of these things are going on in the brain during a fever, right? So in the same way, we know, I would say, probably about 20 things that are pretty decent explanations for what's going on in the brain during depression. So I don't know, I don't like this idea that we don't know what's happening with depression. We know a lot of things that's happening in depression, and we know tons of things that are linked with worse depression. But I agree that it's like, very complicated. I need to do a whole episode on it and just do a deep dive on like, every single

• 1:30:12David Puder?

  theory and the research behind it, and then where we are today with it, because things have changed, too. But but go ahead. Keep going.

• 1:30:20Speaker 01

  Yeah. So yeah, I completely agree because as we spoke about before, some of the mechanisms for exercise, like we mentioned things like BDNF, we mentioned, you know, increases in neurotransmitters like serotonin, norepinephrine, dopamine. This review was, as I mentioned, just published in 2024, and they took a different lens to it. So they wanted to propose a novel hypothesis for understanding the antidepressant effects of exercise, but this time being more centered on motivation, which I think has utility because it's a large component when you're speaking to a patient about exercise and motivation is a large factor that will influence their ability. So I think this is something that's helpful to talk to your patient about and structure it around this mechanism because it might resonate

• 1:31:03Speaker 01

  with them. So what they stated was that depression is associated with disruptions in several closely related neural and cognitive processes. So as I mentioned, including dopamine transmission and affects brain connectivity, reward processing and motivation. And previous work has shown that there's evidence to suggest that the motivational symptoms of depression, so that a motivation that the patient is experiencing can be related to levels of inflammation. And we know that inflammation in itself is known to reduce the transmission of dopamine, which dopamine is strongly implicated in effort based decision making for reward. And we know that things like exercise, so particularly aerobic exercise,

• 1:31:46Speaker 01

  is known to decrease systemic inflammation. So the hypothesis here, without getting into all the nuances, was that by reducing inflammation and boosting dopamine transmission, exercise can improve what the authors deemed to be, quote, interest activity symptoms of depression. So more the motivational lens of things, namely atidonia, fatigue, subjective cognitive impairment. And by doing this, you increase the patient's propensity to exert effort. So from this, you can kind of reshape how cognitive impairment and depression may be conceptualized through the effort based decision making framework, which may help explain the impact of exercise on cognitive impairment and depression. So I think it's

• 1:32:31Speaker 01

  interesting to frame it this way because it's a new paper. It's interesting to speak to your patient about how Depression, that e-motivation may be preventing you from engaging in exercise, but at the same time, explaining the mechanism to the patient that, hey, maybe the exercise itself can help with that side of things and really get that ball rolling.

• 1:32:51David Puder?

  This is a great paper, great find. They did a wonderful job summarizing very complex, synthesizing very complex things, especially anhedonia, right? Depression, especially anhedonia, they cover looking at how it's associated with increased inflammatory cytokines and other markers of inflammation, disrupts dopamine transmission, reward processing, and how exercise can can help in that. And I think that makes sense to me. And there's a lot of evidence there to support that. So I think I think there's something about exercise. It's like you're doing something. This is what I coming back to like, like the cognitive

• 1:33:32David Puder?

  behavioral approach to treating depression is like you're taking small steps and actually doing something physical. And there's something about that that's very important that we need to embody. Brendan, any, any thoughts on the mechanism or?

• 1:33:49Speaker 02

  I, I think this is a great paper and watch out because John Ross and colleagues who are doing this have a welcome trial where they're looking at the mechanisms. And I think this is a great prequel to their trial, which they're currently doing at the moment. So I think when it comes to looking at the neurobiological and psychosocial mechanisms of the antidepressant effect of exercise is we really only have snippets of different pictures. We've got lots of individual theories and we've got small bits of data from each of these different areas, from the inflammation hypothesis, from neuroplasticity, from changes in structure and function within the brain. And these are correlated with changes in trials in depressive symptoms.

• 1:34:31Speaker 02

  But really, if we think about what's happening when we exercise, so much is happening and we tend to just look at one pathway or another pathway. So bringing these together is really, really powerful. And I think what these authors do really well is tie this together with some of the key components of depressive symptoms. So watch out for John Ross and colleagues at UCL who've got this really, really exciting trial to bring across multiple different systems together. And I really hope it does bear fruit to help us explain the antidepressant effect of exercise.

• 1:35:01David Puder?

  Very cool. You'll have to introduce me to them and maybe I can get them on my podcast eventually. With with both of you to to discuss their paper, that would be fun. All right, let's go into how to prescribe it. I know we've talked about this somewhat, but let's hit on things we haven't hit on. I know we're writing a paper on this as well, so let's talk. Nicholas, you want to take it and go into it?

• 1:35:24Speaker 01

  Yeah, for sure. So for this, we won't get into the super detailed aspects of it, but more so to discuss a framework of how to prescribe exercise for depression. And as you mentioned, we actually published a paper on this in in sports psychiatry of how to prescribe exercise for depression. And the main points to highlight is, you know, as we discussed at the beginning of the podcast, when you're prescribing exercise, you can't just say, hey, go do exercise, come back, see how it's going. Because you wouldn't do that for a medication either. You wouldn't say, hey, you know, take escitalpram. I'm not going to tell you the dose, how to take it, like, just, just take it. It wouldn't be fair to do that sort of thing.

• 1:36:09Speaker 01

  So we took the parameters that are previously published in in terms of how to make a framework where with a medication, you have dose, frequency, the route of administration. With exercise, you have the frequency, intensity, type and time, and that's the FIT framework. So F I T T. And just to very quickly go over some of those parameters. So frequency is how often someone is participating in physical activity. And there's, as we mentioned throughout the episode, you know, a lot of different metrics that you can use in terms of what is optimal, but really discussing with the patient, starting low and building up from there. Intensity is how much energy is expended during the actual physical activity itself. And as we've discussed, you can measure that in a variety of ways,

• 1:36:52Speaker 01

  like how many minutes you're exercising, what your METs are, sort of thing. But a simple, practical way for patients is oftentimes intensity is broken down into low intensity, moderate intensity and vigorous. And something that's useful is called the TALK test. So rather than having your patient monitor their heart rate, monitor their VO2 max, all these complex parameters, you can say, when you're exercising, if you Can talk, you can sing, you're probably at a low intensity. If you're able to talk, but it's getting a little bit harder, like you can't really sing, you don't have the air capacity to do that, you're probably at moderate. And if you're exercising so hard that you can't even get a few words in, you're probably at the vigorous intensity. And that's a good kind of way to measure it, not perfect, but it's very practical.

• 1:37:37Speaker 01

  Um. And then timing wise, as you know, how long are those sessions? And we spoke about different durations for there too. And the principle again is just setting manageable and realistic goals and working up from there. And then the last part is just the type of exercise. So is it aerobic? Is it resistance? Is it mind body? Or is it a mix of them? Um. And as we mentioned before, the importance is selecting enjoyable activities that lead to greater adherence and long-term success. Rather than, you know, specifically picking this exercise because it's the quote unquote optimal for this this condition. Um. But those are kind of the overarching themes. So if anyone has comments with regards to that, um.

• 1:38:16Speaker 02

  Right. Great summary, Nick. I think the thing that that I would do when I'm working with someone is I would, I would just trying to get it personalized and individualized, trying to understand where someone is currently. It's a bit like the the the three or five A's um framework for smoking cessation and where you're asking and you're understanding. I'd have some kind of assessment. So I'd want to understand perhaps using using the frequency, intensity, time and typing, I'd say, how much? How much are you currently doing at the moment? How much walking or movement are you doing? I'd go through some intensity. Hey, I'm currently doing X, so I'm currently walking here or I'm going here and okay, how does that feel when you're doing that? So I get some kind of inclination and then once I'm able to do that, I'd perhaps tailor what I'm doing with that particular person. And often I find what's helpful is

• 1:39:02Speaker 02

  which reflects what we've discussed around the literature, I will talk about the the small amounts are really beneficial for people. Depending on, I mean, if someone comes in and says, hey, I'm doing three hundred minutes per week, then I wouldn't. But for most people who are really struggling and got very low levels of physical activity, which is about fifty percent of people when we've got accelerometers on them with depression. Um. I would, I would emphasize that small amounts, very much with that U-shaped curve we discussed earlier on, that if you're not doing much at the moment, then just doing small amounts is really beneficial and review it next time. I would emphasize that consistency or frequency is the most important thing. I would be saying at this moment, when we're first getting started, intensity. Um. It's less important. We can work on making it harder. Once you've got into a bit of a habit. And importantly, I would start understanding someone's type.

• 1:39:48Speaker 02

  So I'd I'd really focus on understanding what type someone wants to do, which you touched upon. I would say, hey, let's not really worry about intensity at the moment. Let's just get you doing something. Let's get you being consistent with something. And and just get people doing something small or achievable at the first instance. That's kind of how I would work with someone in that in that framework.

• 1:40:07David Puder?

  Okay, um, Brendan, so let's do a little bit of a role play here, okay? And I'll just tell you, tell you how it's been for me lately.

• 1:40:17David Puder?

  Okay, so.

• 1:40:17Speaker 02

  Go for it, David.

• 1:40:18David Puder?

  So, you know, I've been listening to Peter Attia and he talks about zone two. So I bought a lactic acid threshold and I I figured out it, you know, at about two hundred and five watts on the bike, I get to about two millimoles of lactic acid. And so, but lately, for me, getting to that place, like, I can't do it for more than like five minutes. And so I went to one sixty the other day and I did that for thirty minutes straight, but I felt kind of guilty that I wasn't getting up to that two millimoles of lactic acid like Peter Attia recommends. Like, do you have any, like, advice for me?

• 1:40:57Speaker 02

  So how hard did you feel you were working when you did your thirty minutes? I get you're feeling guilty, David, and that's understandable when you're listening to such an eminent expert as Peter Attia. But if you had to rate how hard you felt you were working, so from scale from not, not at all to ten, I was completely flat out, couldn't go anymore. How hard did you feel you were working for that thirty minutes?

• 1:41:17David Puder?

  Uh, it's probably a four or a five. It wasn't, it wasn't too hard. Yeah.

• 1:41:23Speaker 02

  And do you think, do you think you could have, you you could have done that for a bit longer?

• 1:41:28David Puder?

  Yeah. Yeah, I probably could have gone for another thirty minutes.

• 1:41:34Speaker 02

  So I'm not overly concerned, David, about uh the you you're concerned about guilt, but I recognize that's important for you. But what I would suggest is that we increase over the next few days five minutes per day. And we just notch up the intensity that you're going for, because it's much more important to just to just to gradually increase what you're doing.

• 1:41:54David Puder?

  Okay.

• 1:41:54Speaker 02

  And if you start to get above an effort of, say, seven or eight out of ten. Um, and then that's the point at which I want you to kind of like stop and uh that particular point, because we don't want to push and rev you absolutely to the maximum. Because what tends to happen when I'm working with people like yourself or lots of other people, when we start to get to that eight, nine, ten level. People can often tend to sort of drop out, find it difficult and then miss a day and even put themselves at an increased risk of injury. And from talking to you, I get the impression that that's not what you want to be doing to push yourself out hard, that you may well drop out or get an injury. So would that sound like an agreeable plan to you?

• 1:42:31David Puder?

  Sounds sounds good.

• 1:42:34David Puder?

  Sounds good. Um, yeah, that's good. I think I think that it's so individual, right? Because like you're talking to me, I'm obviously someone who's been training and someone who's conscientious and curious. Um, where a lot of patients, it's like, okay, how can we go from one thousand steps a day to one thousand five hundred? You know, and like, let's make that our first goal.

• 1:42:58David Puder?

  Which like I open up my my step app and without even trying, it's like six thousand. So it's like one thousand is barely getting out of bed.

• 1:43:07David Puder?

  Which is some where some people are. So, okay, uh, yeah, any other overcoming barriers to physical exercise? Do you want to talk about that?

• 1:43:17Speaker 01

  Yeah, sure. Yeah, I think like in depression, common barriers barriers to like expect in someone that's experiencing a depressive episode are things that we mentioned before. Like the the low energy, the lack of motivation. Those are important things to talk about with your patient and and setting those realistic goals. But other things that we know is, you know, people that are coming from a lower income or a lower SES. Um, or that have more medical comorbidities are more likely to experience depression too. So it's important to look at that whole picture. So specifically with regards to like low income, we know that. Sometimes exercise, we think it's very accessible, but it may not be accessible to everyone.

• 1:44:00Speaker 01

  So we know that in lower income neighborhoods, green space availability is significantly less available compared to when you look at higher income neighborhoods. So it may be infinitely harder for that person who just wants to go outside for an enjoyable walk, or what you think from as the physician that might be easy. I think it's important to really discuss that with the patient and see what they are able to do in their situation. And there have been some reviews on this topic. And with regards to the motivation side of things as well, too, sometimes setting those early goals is the hardest thing. And a useful strategy that has been shown in the literature is something called the commit 10 approach.

• 1:44:40Speaker 01

  So it's where as a person, you commit just to 10 minutes of physical activity per day, and then you have the option to continue if you're feeling up to it. And this can be a very helpful way to get into things because you're setting a lower goal versus as we spoke about before with the FIT framework, it can be overwhelming when you're a patient. And if your physician's saying, hey, the optimal amount is three to five times per week of 45 to 60 minute sessions, that's a lot of mental burden, but that's also a lot of time out of someone's day who maybe is working 12 hour days. Maybe they have, you know, kids at home, they have a lot of other responsibilities, and it can be disheartening for the patient. So setting that initial lower goal is so important.

• 1:45:24Speaker 01

  And as Brendan mentioned, like that gradual progression over time is so important, too. So you can start with those small achievable goals that allows the person to really build confidence and start incorporating the physical activity into their routines day to day. So it's less of a active mental process to remember, hey, I have to run, or hey, I have to go to the gym or go for a walk, but it becomes part of their day. And again, emphasizing the main point that Any amount of physical activity is beneficial and any setbacks or missed sessions shouldn't be seen as a failure. It's part of life. Like as you saw even in the RCTs where they had so much support, they had different trainers, et cetera, et cetera. The adherence was still not

• 1:46:09Speaker 01

  perfect and that's okay, right? That's what the real world looks like. So not to promote physical activity as this perfect thing where if you're not working out X minutes at X time, it's not worth it. Like any amount is really helpful. And as a physician, you can use some of those motivational interviewing techniques for patients to express their reasons for change and reflect the reasons back to the clinician to really get someone motivated. And then the main thing is involving the patient in setting up that plan and being flexible. And with that, you'll find more success than trying to apply this cookie cutter approach to each person in front of you.

• 1:46:45David Puder?

  Awesome. I think this is a great place to to bring it to a close. Any final thoughts, Brendan? Any any final reflections? Any final sort of summaries that you want to put out there?

• 1:46:57Speaker 02

  For your own personal interest or for the people that you're working with sport, encourage people to go and have fun. I think that's the most important ingredient with all of this, all we're getting moving. Fun is just so important and it should be part of a joyous part of a daily activity. So that would be my main point.

• 1:47:13David Puder?

  Yeah, that's good. Yeah. Nicholas, any final final closing thoughts?

• 1:47:18Speaker 01

  No, I think I echo the same thing. It's similar to any lifestyle intervention. You know, you want to have fun, you want to enjoy it. But at the same time, you want to give it like a go, a fair chance. Because my own personal anecdote was I was someone who my whole life I played soccer. I played at a higher level. And then when I got to med school, you know, it wasn't the same when you're not playing competitive and stuff. So I was apprehensive to go to the gym. I was like a, you know, smaller guy, didn't want to go sort of thing. And then when I first went, I didn't like it as much, but then I got like just addicted to it. I just loved it sort of thing. So I think on top of having fun, being open to experience and just giving it a go, because you'll never know what you really enjoy until you give it

• 1:48:00Speaker 01

  a fair shot. So I think that's one of the biggest, biggest points.

• 1:48:04David Puder?

  That's great. Yeah. Nice. I would just add as well, try to get out in nature and give, give nature a go. Cause there's something about doing exercise in nature that's for me wonderful. Yeah, it's, it's a pleasure. I mean, it's not everyone has green space that's right next to them. But if they do, go, go try to get out there, you know? Beautiful. Well, hey guys, this has been wonderful. I really appreciate you Nicholas, Brendan for coming on. You're true experts on this topic. And I think the handout is wonderful as well. I know you guys are active on Twitter or X. And you can follow up with them there as well for their ongoing research.

• 1:48:45David Puder?

  I think it's a great place to see what, see what's coming out and the very, very active posting. So yeah, we'll leave it there for today. Thanks for coming on.

• 1:48:55Speaker 01

  Thank you for having us.

• 1:48:56Speaker 02

  Thank you.