Zepbound Anhedonia Affecting Pleasure for More Than Food

Added: 2026-05-05

[00:00:01]One of the biggest topics that we have talked about over the last few months here at On the PEN is the topic of anhidonia. That part of your brain that just kind of goes about things other than food on a GLP1.

[00:00:14]If this is something that you have experienced, you're going to really enjoy this conversation as we welcome back uh one of the most outspoken uh physicians on the topic uh online. Uh actually probably the only one that I've really heard talking about this topic.

[00:00:29]Let's welcome back in Dr. Spencer Nadulski. Spencer, welcome back.

[00:00:32]>> As always, a pleasure. Big farm shill right here for you.

[00:00:36]>> That's right. He's joining us from his yacht, the SS Eli Liy, floating out off of the coast of the Atlantic Ocean. So, appreciate you taking a moment to join.

[00:00:44]And this uh satellite internet is working really well, too. I'm sure that >> Lily will get the bill for that, too.

[00:00:50]Um, but yeah, always good to have you here, man. And always appreciate the perspective that you share online. I know that um probably most people in the on the penin community already know who you are. You've been here a couple times and they've probably seen your stuff, but for those who don't know, just a quick introduction, let them know about who you are, where you come from, and why you do what you do.

[00:01:09]>> Yeah. U board certified obesity medicine doctor. Started with family, then did the obesity and actually uh something called lipidology.

[00:01:17]Uh board certification. I'm the guy who started sequence, which got bought by Weight Watchers. I left them, created my a new more evolved program. I would call it called Vineyard. So that's what I'm doing.

[00:01:28]>> It's called It's called Better Than Weight Watchers, which I think is a really good name.

[00:01:32]>> They they they're they're big lawyers may get mad at that, but yeah, something like that.

[00:01:37]>> My name my name, not your name.

[00:01:40]>> So yeah, that's what I'm doing now. I big into resistance training and we're doing a lot of research and body composition while on these medicines.

[00:01:47]But uh that's that's the gist. Yeah.

[00:01:50]>> Yeah. So, so now you're running Vineyard uh and you're you've got a comprehensive program over there. I know a lot of folks from the on the pen community have have tapped into what you're doing over there. So, appreciate the fact that you uh went at it again and kind of brought your your uh perspective to uh to Vineyard and I've I've loved following what you're doing there. So, let's get to this topic of anidonia because first of all, you're you're like maybe the only doctor that I hear really talking about this topic routinely. And I think it's one that has to be like we need to get this one out into the into the discussion, the meta discussion that happens around these drugs because one of the things that I find interesting is the push back. Sometimes you get just the staunch like people who defend GLP1s at all costs as if they have no trade-off whatsoever and universally they're great for everyone. Um I think for the vast majority of people and we talked about this before we even went live like think at some point most people will be on these for one reason or another. But there are trade-offs just like there are with anything. And one of the most interesting things that I found covering the Eli Liy earnings calls for the last four years is that one of the one of the ways that they routinely refer to the class of medications is anti-hedonic medications. So Spencer, first let's talk a little bit about how these drugs they're doing a lot of things metabolically, but they're working in the brain. How specifically are drugs and let's talk about trespathide specifically because I think that's the one that we hear the most about this issue with and you can chime in if you have different experience but how does trepatide work in the brain?

[00:03:23]>> Yeah. Well, so it's both a GLP-1 and GIP called a co-ceptor agonist. Now there's a lot of debate on how much the GIP uh is additive versus synerg synergistic. If you know simaglletide and the ones before it were all just monoagonist mono receptor agonist just GLP-1 well tepatide hits two receptors but there's also this component about it it's a it's a biased GLP-1 receptor agonist meaning it has different downstream effects uh more targeted downstream effects than say saglutide and one of the things that people think about it is that it it actually keeps the receptors from being uh taken in and degraded so that maybe have more receptor sensitivity. I don't know there when I talk to the big- time researchers who are like literally looking at this on a molecular level they even debate about this regardless is the most powerful thing we have right now best to tolerated uh you know until we get retatriutide coming out looks like more weight loss of course but there are receptors in the brain that then have downstream effects further downstream in in the brain and now we talked about this before where yes, it's appetite.

[00:04:43]It's helping people reduce their calorie intake. But it's not just hunger. People feel that satiety or satiation sooner with meals and they have satiety between meals to where they're not as hungry. I mean, everybody knows what that feels like. You're you got this kind of feeling, those hunger pangs in your stomach where it's like, I just I'm just hungry. Then there are cravings where you're like, I could go for some salty, starchy, fatty chips. that that's what I I I like a lot of times or French fries or whatever, something specific. Then you talk about the food noise and that's a little bit different. You've talked about this all the time on your podcast.

[00:05:22]Just thinking about food intrusively though about all sorts of It could be anything. Uh and people get mad whenever I try to explain food noise because they're like, "That's not the way I have food noise." I'm like, "Everybody's a little bit different." But it's it's all kind of similar very intrusively. just constantly thinking about all sorts of different types of foods. And one of the things that about these medicines that it may that maybe they work a lot better than other what we call anorctic uh drugs like fentamine in the past. It's an older drug that came from the in the 50s60s. It's a has an adinuric effect like empmphetamine like effect but it it reduces hunger but it it doesn't work nearly as well as these drugs. These drugs make you not even think about or want the foods anymore. Not only you're not hungry, but people eat when they're not hungry. And and that's a big issue because if you're eating when you're not hungry, it doesn't matter if we reduce your hunger, you're still going to eat.

[00:06:20]Whereas these just kind of I talk about the the scene in the Matrix. Are you a Matrix fan? You're you're probably my >> It's been a few years.

[00:06:29]>> Yeah. Well, Neo, you know, Neo is talking to Morpheus and he's Morpheus is trying to tell him, "You're the one."

[00:06:35]And he's like, "What are you saying? I'm gonna be able to dodge bullets and Morphe is like, "When you figure this out, you you won't even have to." And then in the scene, it shows later it shows u Neo like dodging the bullets and then finally he just kind of like puts his hands up and the bullets fall down.

[00:06:54]The these medicines essentially make it so you don't even have to you don't even have to stay away from the food. you can be around it and you just don't want it anymore.

[00:07:03]So there's the receptors in the brain that and again I'll speak with neurobiologists about okay because every every few months there's a new thing well it looks like these drugs work here and they try to knock knock knock out receptors and do all these things and compare the the two uh in in rats and animals and see where these are working specifically.

[00:07:26]But it no matter what these these are getting to the part of the brain that controlled our like our reward center and and the wanting and the dopamine wanting of things especially food. And so that's that's really how they work.

[00:07:41]They help us just like not eat things that we wanted in the past. It helps us navigate our obesogenic environment to where we just couldn't do it before. It helps us eat. It helps us do all those things. We know what to do but like just couldn't struggled to do them in the past and and there are a lot of different receptors in the brain and it GIP may be a component of that or it may be that the GIP may help synergistically with the GLP-1 do it even better. Again, a lot of debate there.

[00:08:12]>> For sure. I find it interest the whole topic is interesting to me because I spent three years the better part of three years at the 15 milligram dose of Drespatide and I really started to feel towards the end of last year like it had just shut too many things off. Hunger was never really one that it shut off completely for me. That's why I appreciate that the fact that you talked about you know the different types of hunger the the hedonic driven hunger or more of the homeostatic driven hunger the microbiotic driven hunger. So, I don't know if it's that my hunger gets you comes from a different place that these drugs don't touch as much as they do on the hedonic hunger. Uh, but they never really shut that off for me. But they shut pleasure and not not they didn't shut pleasure off, just the desire for it. Um, and so I just found that I wanted to sort of like just wash it out of my system and see how I felt off of it. And the the comp the the comparison was really stark because when you when you live on a drug and a do high high dose of a drug for a very long time, three years is a pretty long time that how you feel is your new baseline. It's your new normal. And so it really wasn't until coming off it like I knew something was not right, but it wasn't until coming off of it that I really noticed a big difference. And it took a few weeks obviously for for that to come back. But uh I found that very interesting. And so we've been talking a lot about about how these drugs work in the brain and the fact that they they do work on the pleasure reward center of your brain and the fact that really there's a lot that we still don't know about how these are working in the brain. Would you agree with that statement?

[00:09:48]>> Yeah. No, I agree. I mean because people, you know, Bill Maher and these other people like we don't even know how these drugs work. It's like, well, no, we we know how they work in a way, you know, high level, but the the places in the brain where we're starting to find where it's getting to, we we no, we we don't know everything about that exactly.

[00:10:08]>> Sure. So when you talk about the fact that these are hormone mimicking drugs and we're talking about trespathide which is a dual aagonist working on two different hormone receptor sites. Can you tell everybody why this is different than than increasing your endogenous like you could just increase your GIP or you could increase your GLP1 endogenously why the effects of these drugs at least as it relates to the brain is so much different.

[00:10:32]>> Yeah. So when we release our own natural GLP-1 and GIP broken down, they're broken down so quickly, they don't even have time to get up into the brain. We do have actually places in the brain that make their own GLP-1. But either either way, the the stuff that we get from a receptor agonist that's not broken down by our natural enzyme called DPP4, uh they are able to get to high levels and get to places in the brain that our own natural stuff would never get to uh in in time until it was, you know, broken down. So that's why that's essentially why I always make fun of these supplements that increase your own natural GLP-1. It's like, okay, it's like pissing in the ocean. It doesn't really matter um for for appetite. It can matter for blood sugar regulation, but um for appetite and that hedonic feeling, you're not going to you're not going to get it.

[00:11:28]>> Yeah. So, at the end of the day, these hormone mimicking drugs that we're taking exogenously are lasting longer, which allows them to penetrate deeper and bind to receptors that they wouldn't make it to. and they're staying there for much longer. So that's like like you said, you could increase take a supplement and increase your natural GLP1. Frankly, you could eat a Cheeto and increase your natural GLP1. It is a nutrient stimulated hormone. So you consume nutrients, your body releases it.

[00:11:56]>> Yeah.

[00:11:57]>> Uh you're never going to get that binding affinity like you do uh orders of magnitude higher with these peptides that have been modified to bind to those receptors for longer and and stay there.

[00:12:07]And so because they're doing that, we don't know everything there is to know about these drug how long these drugs work and what the implications of that are. What we do know again is that the drug companies themselves refer to them as anti-hedonic drugs. That was sort of the the basis of their investigation of these molecules. We do know that the next generation of GLP1 GIP from Eli Liy is called brenipotide.

[00:12:35]And while there are some phase one studies in obesity, it is a once a month that is being tested in all neurological uh things. It's being tested in major depressive disorder, smoking sessation, alcohol use disorder, opioid use disorder, and even asthma, oddly enough.

[00:12:54]And so this is the next generation of these drugs is all neurological. So when you think about a what we don't know because there is a lot of information that we don't know about these medications and what science is starting to point to these things are working profoundly in the brain and anytime and you can correct me if I'm wrong but I I I tend to believe that anytime a drug is penetrating the brain crossing the bloodb brain barrier it's going to work generally the same but people are going to respond to it differently. Is that fair to say?

[00:13:26]>> Yeah. Yeah, I see all sorts of different responses. Yeah.

[00:13:29]>> So, tell me about the first time you started to identify a pattern of folks using GLP-1 therapy and coming to you and saying, "I'm just feeling a certain way." Did you how'd you start to identify that pattern?

[00:13:42]>> Okay. So, do we we all remember when there was a scare of I believe it was saglletide or it might have been luragiders and saglletide a couple years ago when they're like maybe we need to add suicide risk to the label.

[00:13:57]Well, you know, I was I was at sequence at the time doing research and look, you know, compiling thousands and thousands of patient data and I didn't really see I didn't see a signal in in there. I was kind of like looking at everything. I didn't I didn't see anything there. I was like, that's that's interesting.

[00:14:14]Okay. And then there more reports came in. Okay, no suicide risk. We looked at, you know, controls and didn't we didn't see a difference. It's like, okay, we can say there's no suicidal risk as far as we can tell compared to some other type of drug or a placebo, but it was a couple years ago. Uh I've I had a few patients that were like they so I I go for the refills. We talk about it. We're like, "How are you doing? How's your exercise? How are you feeling?" And they're like, "It's all right, but I you know, I just don't feel like I haven't been exercising as much recently." And I'm like,"Well, why not?"

[00:14:51]They're like, "I just don't feel like it." And I was like, "Tell just explain it a little bit more." And the thing is, I wouldn't have known until I just kept kind of digging and asking.

[00:15:03]And it was because of that patient that I started asking more people and they were on the 15. I started asking more patients on the 15. They're like, "How are you doing?" Like, "I'm okay. Do you notice anything?" "No, I'm I'm I'm doing well." I'm like, "Well, what about like your hobbies and like what do you enjoy doing?" like, "Well, now that you say that, I I just thought it was a seasonal effective disorder, my usual depression.

[00:15:23]My doctor increased my SSRI. It didn't really help. I don't know." And I'm like, "Okay." So, this was like a couple years ago. I started reducing their doses and go like, "Just in case, let's just see if this is the medicine because what you're describing is anhidonia."

[00:15:37]Just it was it was not depression. It was like a It was just like they had this lack of motivation to do anything.

[00:15:44]Can you can you camp out just for a second on the difference between the two generally speaking?

[00:15:49]>> Yeah. So, like a depression is truly their mood is is lower and they they don't they it's just I don't know. It's it's is ahidonia they're they're just flat. They didn't have ups either. They didn't have downs. They just felt flat. Whereas like with the depression, they they can feel they just they feel down. Um they they don't they didn't want to do anything and it didn't have anything to do with motivation. They just felt like sad and and down and out and but then sometimes they would have ups too. Um they they'd have their higher moments.

[00:16:30]Whereas with uh the anhidonia, they would they would mention that they just didn't have ups, they didn't have downs, they just kind of I don't know, they just felt like the the one in specifically was like they just loved exercising and they stopped and I was like, well, that's the opposite of what we want. I reduced them to 10 milligrams and they were also in a plateau. I reduced them to 10 milligrams and in a few months they lost like 20 pounds after after being plateaued on 15 for multiple months. We reduced them and they lost I don't know it was like 10 to 15 or 20 pounds something like that.

[00:17:12]They're like I'm back back in swimming and working out again and I feel amazing and I'm like okay maybe just a coincidence but I started doing it with a ton of patients. People are like I hated cooking now. I used to love cooking. I used to love planning events.

[00:17:28]I used to love doing XYZ gardening. And now I just haven't gotten out to do it.

[00:17:32]I just didn't feel like doing it. And every one of these patients, I've dropped them down. And um they don't always lose weight from it, but they feel immensely better.

[00:17:44]>> And it doesn't happen to everybody. It's it's um I wouldn't say it's I it's not it's not it's common but not like I would say maybe 20% of patients on the high doses are start are feeling it but everybody now I ask and the reason I say >> when you say when you say the high doses do you mean 10 to 15 >> 10 to 15 but I once in a while I'll see it at a five and a seven and a half um it's rare but I do see it once in a while at those lower doses Do you see any correlation at those lower doses as people who were hyper respponding early on or is it just kind of all over the place?

[00:18:22]>> It's it's all over the place because some some of these hyper I know because you would think that if they're super sensitive to the drug they they can get it. I haven't know I haven't seen that but again I you know this is just all anecdotal. I'm just kind of trying to monitor. It'd be cool to this is this is where a randomized trial would be really really cool to see. Um I think before this we were talking about how in this article that was just posted up the the companies are like we don't have any data on it. I'm like well yeah I I wouldn't have either. I just had to ask and kind of dig into it.

[00:18:58]There are actually anhidonia um uh questionnaires and they're just slightly different than the usual PHQs that we use for screening for depression because it's it's it's just slight it's it's it's a loss of of like like a loss of pleasure desire. Um I and what describe what you felt because it's >> what you're describing is just kind of it's it's the same thing. I'm seeing it.

[00:19:24]>> Yeah. I I will say uh the article that Dr. Spencer is referencing here is this article that was posted in the Washington Post today and uh Dr. Spencer's also quoted in this article because he's been one of the doctors that's spoken on this. It's also features uh Corey Stevenson from our community. Corey was a big part of our our live show that we used to do and and Corey was probably the first one in the online community that started going ra waving a flag on this and going, "Hey, like I stopped being able at the very high dose of of Zepbound to be to do basic things that I used to really be I used to be really organized and I'd pay all my bills on time and then, you know, like all of a sudden it was just hard to to get motivated to do the things I needed to do." And so, uh, if you get the chance to check out that article, it's called what is ompic personality. I hate the name, but I I get as somebody who has to make thumbnails and write articles, I get it. Uh, but check that out. And, um, and it'll be interesting for y'all to hear her perspective. Uh, but for me personally, I think what I started to notice is there were things when you say when you said hobbies that that jumped out to me because I, you know, I had head down for three years building on the pen right into into my my career basically. And so I was working a full-time job and doing this. So it wasn't as if I was incapable of doing anything which almost was probably a false sense of security because what I did notice is I no longer cared about things that I used to love.

[00:21:02]I used to love Major League Baseball.

[00:21:04]Now I've I've had I don't know if you know Dr. Rachel um psych psychiatrist specializes in obesity. She's been on the Oprah show.

[00:21:12]She's she's great. She just released a book. Um she was on and I was I was like, you know, I I used to enjoy baseball and Cubs baseball and it was like I was an avid fan. I'm not a huge sports guy, but I've been a diehard Cubs fan. Didn't care last couple years. Just didn't care. They had decent teams too for the first time since the World Series. And I just was like, and it she's like, "Well, maybe maybe it was something you used to do when you watch the games and you' enjoy." Well, I used to listen at work. I worked some pretty crappy jobs. So, I don't think it was what I was doing. Maybe it was giving me an escape. But I I generally realized that was maybe one of the first things that I noticed that I just don't have a desire for this anymore. And then I will say there was a natural sort of decline in in libido. Um, again, this is never something that I I never lost pleasure for anything. It was more the drive to seek the pleasure. Does that make sense?

[00:22:03]>> Yep. No, that that's that's right.

[00:22:06]>> And so, and so for me, that's that's really what I started to identify and I thought, you know, I I I don't know what I feel like off this drug anymore because I've been on it for three years.

[00:22:16]And it's it's done a mar I mean I want to be clear when I talk about this because I I talk about my experience and I tend to be animated and dramatic when I talk about it because it's my experience. I've lived it. I'm passionate about it. Passion about everything I talk about. I don't want that to be misconstrued. I this drug is a miracle. It's allowed me to live as a type two diabetic and feel every day like I'm not type two diabetic with normal blood sugars. In the month that I was off GLP 40 days I was off everything. My blood sugars went from running around 98 to 100 on average to peeking over 200 in the morning.

[00:22:51]>> Like it was intense. Now, would that have maybe leveled out a little bit after my body regulated? Maybe. But that was terrifying.

[00:22:58]>> And it was like a reminder like, "Hey Dave, >> you're diabetic." Um, and so now I'm back on with this idea that it's a tool for me. It's never going to be the tool that gets me to skinny, which is probably what I thought three years ago, right? That was what I thought three years ago. I think I needed that time to rewire my brain and and understand that this is a tool in a arsenal of tools and nothing is more important than me feeling good enough to show up for the people that I love because it's not just about being here for longer >> if I'm a zombie. So, I'm I'm playing this very slow titration game and I'm very in like you love the conversation of customized doses and customized formulation compounds, but >> I really I do with the quick pens all the time. So, >> yeah. Yes. Yes. So, I mean, I believe that the clinical trials were designed for the masses, but I think for a lot of people, they would benefit from incremental dosing that doesn't go up quite as much because I think people can respond and that's what I've seen so far. And so, I plan on being at these.

[00:24:06]That's my >> sort of >> yeah, >> take on it.

[00:24:10]>> So, I mean, we're we're publishing a paper on this, but um and I'm not going to be the guy who does the placebolinded randomized trial, but I think so. Here's what I do. I I lower people's doses. If they're on 15, I go to 10. I go, look, if this is what's causing because there could be it could be seasonal effective disorder. It could be regular depression, you know, it could be a few other things that are going on, but I want to get the signal quickly. So, I lower them from 15 to 10, sometimes seven and a half. Um, and then we they'll know within about a month.

[00:24:45]They'll they'll just they'll feel different. If some people though still then their food noise and and their and their hunger comes back. So then I go okay sometimes we inch them back up especially if they have a a quick a quick pen we can go to like 11 milligrams or something like that. Um sometimes we go to 12 and a half and they start feeling it again. So then we go back down to 10 and then I add in like Wellbutrin or something like that.

[00:25:11]uh well wellbutrin is usually the one I go to because it has an effect on dopamine and it can help with weight a little bit. So that's that's usually my easy little protocol. But these um there I I'll bet the farm that there's an effect here. Uh big pharma just needs to actually like ask the patients when they're in these trials. They have to actually you can't you don't know what you're not you know testing. So >> it's kind of like whatever if it's whether it's COVID. No, there's no COVID because we're not testing it like whatever. I don't know. It could be spreading around. I don't I don't know.

[00:25:49]But it's it's like there could be anhidonia. You don't you don't know if you're not asking about and doing the right questionnaires.

[00:25:55]>> Um same thing, you know, kind of the same thing with like the muscle the question of muscle loss. It's like, okay, well, we got to actually study it here.

[00:26:03]>> So, um you need the right way to actually test it. So I I I'll bet the farm that there is there is a clear I mean because it's very clear when we'll go down in the dose and go back up and we we watch and they they can feel it.

[00:26:18]Um ideally again you need a placebo to go against or or um not let them know the dose and start changing it and monitor how they're feeling. But anecdotally uh I will bet I would bet the farm that there's an effect.

[00:26:33]>> Yeah. So when we talk about bipotide, the next generation of GI GLP-1 and GIP from from Lily, do you think when we talk about depression, I could I'm way out of my league here, so so correct me when I'm inaccurate, but when somebody comes in and they're diagnosed with depression and they're put on an SSRI, the the SSRI effectively is leveling out their mood, like it's a mood stabil izer, right? But often times people complain that that they don't get the ups with that. They're not getting the downs, but they're also not getting the ups. It kind of tracks with what you're saying anhidonia does, right? I mean, it's it's not here and it's not there, but is that perhaps why it works?

[00:27:23]>> Yes.

[00:27:24]My it that's actually a really it's a it's a good it could be bringing up the lows while bringing down the highs. I don't I don't know honestly. I this this starts it and this is the thing. I don't think they really know but if they're studying it they they they know there's something clearly if they're looking at it for depression. I mean we see you can see the the they aggregate all the data and they because they've been worried about mental health and it looks like on average less anxiety less depression but again it's anhidonia can be a a component of the depression but it's also it's it can be its own thing um so I do think that they're going to need to look at this very closely and it's it's this is why I do think there are sweet spots talk about like customized dosing >> people will they're gonna be like no if I go higher I mean I I've had a few patients a day like now we got to keep at this dose because if we go higher that's when I start feeling just like I'm not going to do anything anymore. So with um bipotide I'm actually really interested because I'm like are they do they think this isn't going to cause weight loss? It's it's modified in a way. I'm not even sure there >> I I don't either because there are I forever I I was like I can't find any weight loss studies on this at all. I guess there are some phase ones and I think it may have to do with the frequency and and amount of dosing because the those those clinical trials and the neurological issues are a once a month injection or once a month treatment. So it'll be interesting. But I think the point that you brought up is really interesting as well because there was a recent study published in the Lancet uh which followed like 95 96,000 people with uh depression or anxiety and semaglutide was the main one that they were looking at comparing it to some of the older ones but uh reduced the risk of worsening mental illness by like 42%.

[00:29:21]So on balance they know that there is a positive benefit. It's like but I I wonder for a certain subset of the population if there's the counter effect too, right? And and so that's where I where I go. There just needs to be a lot more studying on this. And that's why and I don't I don't know that you necessarily agreed with this, but >> that's why when they removed the FDA went to remove the suicidality warnings from this, I thought I don't know if I love that because we don't know how this works for everyone.

[00:29:54]though we have these studies that kind of point in that direction that it's it's actually protective. Is it for everyone?

[00:30:02]>> Yeah. The way that it's so there's there's not a signal for suicidality, but I the the what I I like to monitor like when when I notice a patient, they're on 15 or they're on like let's say they're 12 and a half of Zepbound or 10 and they start moving up, I always say, "Hey, you know, I'm I'm increasing your dose. We're going to see if we're going to get a little bit more weight loss." But start just start just paying attention to hobbies and how you feel about things. So I think to me I think the label should be more like again they have to study. They're going to say well we don't have a signal for anhidonia.

[00:30:36]It's like well you didn't you didn't look at it. So but they know that there's some effect on mood. So they should probably just say hey uh it would be a good idea to monitor mood. You should you I mean you should no matter what in a primary care setting, but you know we got a lot of tele medicine places just sending it out and uh it would be it'd be good just to have like a quick question. Hey, is your mood changing? Have you noticed anything?

[00:31:01]It's so it's super simple but you don't know until you ask.

[00:31:04]>> I know that I know that Rorow does that by the way. There's there's a monthly >> uh there's a mental health checklist on your monthly check. Um so so they're compiling that data which would be interesting to see long term.

[00:31:17]One of the things Spencer that um you were talking about that kind of stopped me is when we talk about these drug companies and in the clinical trials and and you know not compiling this data on the front end. What I struggle with and and I think this is interesting in light of a news story from this past week.

[00:31:38]What I think is interesting is you got Dave Ricks walking around calling it an anti-hidedonic medication. And anti-hide is literally the word anhidonia.

[00:31:46]there had to be some sort of inclination that this could go the other way for people and probably would have been a good thing to track. And that's where I go to back to this last week. The FDA um basically put out, you know, a memo saying that 70% of the drugs that are currently on the market do not have complete data in terms of all of the negative data that was compiled into clinical trials.

[00:32:16]I got to think that as patients, we ought to be demanding that because everything that we talk about here at On the Pen, again, I'm obviously not a doctor. I have no background in medical to speak of. I'm just a guy trying to figure myself out and sharing the news about medicines along the way, right?

[00:32:31]But I I really believe that in the long run with these medications completely completely lost my train of thought. What was that?

[00:32:47]>> Well, you they should be trans. They should be extremely transparent about this because we don't want to have we we we went through fenfen and I was just a little tikeke back then in the '9s.

[00:32:58]didn't know what the hell is going on, but like everybody's scared that there's a smoking gun here. So, we need all that data to go like to put those fires out or to bring them to light to just to monitor. I I I agree. We need transparency. Otherwise, I'll get man because I'm a I'm a big shill for these medicines as are you.

[00:33:18]I and I'm like backing them up, but it's like if there was something there that like big pharma did for some reason held back and that would make me upset because it's like I don't want to play interference for big pharma. I don't pay me enough for that.

[00:33:33]>> Yeah, I don't I don't neither of us uh neither of us actually have a yacht although I think we're both holding out for one. Um, but yeah, that was thank you for finishing my thoughts because that's what I was trying to bring it back around to was p everything we do here is designed to give patients information so they can take it back to their doctor and go, "Hey, doc, what do you think of this guy on the internet said this? What do you think about this?"

[00:33:54]>> And it's like if we because at the end of the day, patients who are engaged with their doctor, I always say that you are the you are the expert in you and your doctor is the expert in medicine and together you guys should be making these decisions. And so being informed is the most important aspect of that whole process. And how can we be making an informed decision when 70% of what's out there we don't have the full picture on, right? And it may not be that profound in all instances. But in some it is and I think that that's definitely something that needs to be explored more with these medications and why I was eager to have this conversation with you because again as as much as these are life-changing medications and you and I both believe that most people at least I believe I think you'll agree that most people at some point will be on some form at some dose of this medication because they've been proven and are continue to be proven so broadly effective. Right.

[00:34:50]>> Yeah. They're powerful. I agree. I I I think I think they're going to be a quality, you know, quantity of life and longevity uh drugs in the long run. I do.

[00:35:00]>> Yeah. And I'm 100% with you. But that said, uh we should be uh always educating ourselves and always endeavoring to learn everything there is to learn so that everybody can be uh informed to the best level possible. I I just that's where I'm at on this. And so I appreciate the fact that you've highlighted this. Now, you you talked about a couple things. You talked about reducing the dose and then sort of incrementally increasing. You've talked about combining uh the medication.

[00:35:30]One of the things that that I experienced when I first started these medications is I was so fatigued of like 20 years of roller coaster dieting that I was like so eager to shed this idea of the diet culture of of really like to me exercise was always a punishment. Like if you were going to eat this then you're going to go run a mile, right? And and so it was always kind of this you don't deserve to eat that and then if you do you deserve to be punished for it. Like that was the toxic sort of relationship with food that I was ready to break up with. In doing so I was so fatigued I was ready to let the medication do the work. And so for the first few months the medication did the work. I mean I dropped 30 pounds in like four months but I went from 2.5 to 10 in four or 2.5 to 15 in four months.

[00:36:20]>> None of the incremental doses were there. And so like I kind of tapped out pretty early on what the medicine was going to do for me from a weight loss perspective. But then I think by the time I was at that 15 for a few months, I just had no desire to to pick back up the things that I once, you know, was pretty routine at doing like resistance training and and you know, being consistent with my nutrition. And so when I took this last sbatical, I I thought, you know, this is the mental reset that I need because I need to I always intended to come back to True Epide, love the drug, don't love it for me at 15 milligrams necessarily, but love what it does for me at the right dose. And so I want to find the right dose, but incorporate it with all these other things that I've always known how.

[00:37:07]And so that's what I'm trying to balance. The second I feel like I don't want to go to the gym, I don't want to do that. Um, I'm just trying to be very keenly aware. What What would you recommend to folks who maybe like me have been on the medication for a long time and maybe don't even know how to identify anymore that they're they're feeling this? Like what are some of the things that they should be looking for and how can they start that conversation with their doctor without being afraid?

[00:37:31]Because I think most people are like, I don't want to tell my doctor he's going to take me off it.

[00:37:34]>> Yeah. Yeah.

[00:37:35]>> That's people's biggest fear.

[00:37:37]>> Like you said before, just kind of the desire. So like um in just any hobbies and it could be cooking. I mean the thing is we we have these addictive like food. So it's good we dampen down our you know wanting of these things but I I think it dampens it down so much to where all of a sudden like little little hobbies like again a patient said they liked planning parties wasn't that they didn't they didn't want to do it anymore. Someone liked going for walks they they like to do that. Exercise is the is the big one. We always ask about that, but um cooking, playing tennis, hanging out, going to movies, even things things like that. If you started to notice that, that's here's how if you're worried about um the doctor taking you off the drug, I would just say, look, you could even frame it as feeling tired or something like I kind I want to drop down in my dose. And again, you're going to have to talk to your doctor. I can't play your internet uh on the pen, doctor. But like I would I would can talk to them about can I just drop my dose for a month or so and I I would be aggressive about it. Um don't don't stop it. I would I would be taking it back, you know, either two and a half or five to know for sure. I like to drop people by five because it's like, you know, pretty quickly and they don't usually gain a lot of weight or anything in in that month. You just have to have constant contact. Don't don't leave for like six months and be like, "Okay, well, I gained 20 pounds in that time."

[00:39:09]You you be like, "Okay, I gained a few pounds, but I'm feeling a little bit better." Like you you'll want to uh pay attention to that. That's how I would talk to the doctor. Um again, wellbutrin is another option if you need to be on a little bit higher dose, but because of the food noise, but you're also feeling um some of that anhidonia, whereas if you go down a dose, you you just get more and more food noise. Um, so sometimes talking about buprop, it's buproprion as the generic name.

[00:39:39]Definitely just definitely have a chat.

[00:39:40]Hopefully you have a doctor that's like cool. And the thing is so many doctors I'm just I'm hearing but they're like you get to a normal like a a BMI that's like 22 and the doctor's like we got to stop the medicine. It's like no, you want to help them maintain the the weight. So people are people are wild.

[00:39:58]I'm hearing all sorts of wild things out there.

[00:40:00]>> I'm I'm sure you are. That's that's why I I just appreciate doctors that make sure that they're well informed. And I can't think of a better drug in my lifetime that every doctor should spend a good bit of time boning up on and following uh some some doctors that are really knowledgeable in this and treat a lot of patients with them even if you haven't because it's just it impacts so many people probably at least half of your patients by the number probably more. Right. So, uh, I think that's great and I think that's good advice because I think that is what keeps people from talking to their doctor is just the fear of losing the medication.

[00:40:35]And it sounds like what you're saying is for most patients that present to you with some sort of anhidonia like thing, you're able to figure out figure it out without taking the medicine away. Right >> there. There's been one one out of like a hundred or so, one patient couldn't tolerate tepatide or simaglletide. I thought it sag was going to do fine. No, they they couldn't tolerate it. Say, and even at the low doses, but most >> and they couldn't tolerate it from a from a mental health standpoint.

[00:41:04]>> Yeah. Yeah. It was it's they were very sensitive to it. So, we ended up using a non GLP-1 medicine. It's working really well, but um yeah, that but most commonly I can reduce the dose and things clear up.

[00:41:20]>> Awesome. Well, I think that's probably going to be very helpful for a lot of people. really appreciate you taking some time to come to OTP and talk to our community about that. Spencer, where can people follow you?

[00:41:29]>> Uh Instagram, Dr. Nadulski, obviously Vineyard. Joinvyineard.com is my clinic if you want to work with one of my great doctors and dieticians. You can docuft podcast. I got a podcast uh with my brother who's an endocrinologist and obesity doctor. So that's where you can find us.

[00:41:46]>> Awesome. Well, thanks for hanging out with me, man. I appreciate uh nerding out with you on this topic. appreciate your willingness to come on and chat with us and I hope you have a good rest of your day and we'll do it again.

[00:41:55]>> Thanks, man.

[00:41:57]>> Appreciate it.