Research Recap with Skye: The Atomoxetine Trial
Welcome to Hacking Your ADHD. I'm your host, William Curb, and I have ADHD. On this podcast, I dig into the tools, tactics, and best practices to help you work with your ADHD brain. Today, I'm joined by Skye Waterson for our research recap series. In this series, we take a look at a single research paper and dive into what the paper says, how it was conducted, and try to find any practical takeaways.
In this episode, we're going to be discussing a paper called "Atomoxetine treatment strengthens an anti-correlation relationship between functional brain networks in medication-naive adults with attention deficit hyperactivity disorder: A randomized double-blind, placebo-controlled clinical trial." Yes, that's the full study name.
If you'd life to follow along on the show notes page you can find that at https://HackingYourADHD.com/272
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William Curb: Welcome to Hacking Your ADHD. I'm your host, William Curb, and I have ADHD. On this podcast, I dig into the tools, tactics, and best practices to help you work with your ADHD brain. Today, I'm joined by Skye Waterson for our research recap series. In this series, we take a look at a single research paper and dive into what the paper says, how it was conducted, and try to find any practical takeaways.
In this episode, we're going to be discussing a paper called "Atomoxetine treatment strengthens an anti-correlation relationship between functional brain networks in medication-naive adults with attention deficit hyperactivity disorder: A randomized double-blind, placebo-controlled clinical trial." Yes, that's the full study name. It's quite a lot. This study is about the push-pull relationship between the Default Mode Network and the Task Positive Network, and how Atomoxetine treatment can be effective in dealing with that. Let's get into it by jumping into some of these terms we’re going to be talking about.
Skye Waterson: I think we should start with some terms. I will say as well, this paper is from 2015, so it's a bit of an older paper, but it was also the paper that really nailed this topic in terms of being a randomized, double-blind, placebo-controlled study. That basically means they did this well. Let's talk about what it is first, then we'll talk about how they did it. Take us through what the task mode and the default mode are.
William Curb: Okay, the Default Mode Network (DMN)—I've done episodes about this and we've talked about it on the podcast before—is something I think is really interesting to discuss because it's the active part of your brain when you aren't focused. It represents the regions of your brain that "light up" during an MRI, which is what we’re going to be talking about in this study.
It’s active during rest, mind-wandering, and self-referential thoughts. It’s the "I'm chilling out and daydreaming" part of your brain. Then, your Task Positive Network (TPN) is active when you're focused on the external world to solve problems and pay attention.
This is the executive function part of your brain that goes, "We're doing stuff." Typically, in a neurotypical brain, you have this push-pull, seesaw relationship: the default mode network turns on, and the task positive goes down. When you start doing work, the default mode turns off, and the task positive network comes on. This paper talks a lot about how that relationship does not work with ADHD brains, and how they try to treat this with Atomoxetine.
Skye Waterson: Yeah, exactly. And for those of you who are like, "Wait, people have a switch that turns off and on?"—100%. That's one of the reasons why we talk about this stuff so much and why we struggle with this.
The interesting thing here was that by treating it in this particular way—and again, this is an example of what we've talked about before—papers don't always come to us fully formed in a way that is made to support people with ADHD; it's often about how to support medication. In this context, they did a very solid study which shows us that yes, Atomoxetine is helpful, but also that there's definitely a difference between the ADHD brain and the non-ADHD brain. To me, that is almost more interesting because it's hard to get the funding to do such a deep dive into this particular topic. It's particularly hard to work with medication-naive adults—people who have ADHD but haven't taken medication—compare them to normal controls, give half a placebo they don't know is a placebo, and then test the results in an fMRI, which is expensive. That's exactly what they were able to do.
William Curb: Yeah. So they grabbed 48 adults. They had 24 medication-naive adults and 24 controls, matched so you had similar populations. Some were given Atomoxetine and some weren't, and then they were popped into an fMRI. One of the funniest things I saw in there was that they didn't have anything to make sure the participants didn't fall asleep in the MRI machine. Everyone reported they stayed awake, but I'm like, who's falling asleep in an MRI?
Skye Waterson: I know! And it was six minutes. I had the exact same thought. They said nobody napped, and we don't think anyone lied.
William Curb: Yeah, MRIs are intense.
Skye Waterson: It feels like a strange place to take a nap. I also want to say that the participants—they called them "patients," which is an interesting use of terminology—fulfilled the DSM criteria for childhood and current ADHD diagnoses. This was not a "do you think you have ADHD? Pop your hand up" kind of study.
William Curb: They were looking at whether this medication actually reduces this lack of anti-correlation seen in ADHD. Meaning, when we're doing a task, do we see a reduction in our default mode network when taking this medication?
Skye Waterson: Exactly. And they're specifically looking at this because those are our external ADHD symptoms—daydreaming while we’re trying to do something else. I’m very interested in the other way the correlation goes, but there is not a lot of research on how, when you’re trying to relax, your task positive network is still going.
William Curb: I find that to be awful.
Skye Waterson: It’s like the medication holiday conversation we’ve had before. They aren't that interested in what you’re doing with your spare time or how that affects your brain; they mostly want to know how you’re getting tasks done.
William Curb: But yeah, they were looking at this effect and whether the medication worked. It was effective in having some reduction there. I think the more important result here is showing that not only does this correlation exist, but it is a function of ADHD symptoms and it can be reduced.
Skye Waterson: I think that was the key. If it was just about the medication, I don't know if I would've pulled a paper from 2015. But the fact that they were able to showcase that there is a very specific difference in the way your brain works when you have ADHD is so interesting, because for a lot of people, it just feels like a personal flaw.
One of the systems I teach—and actually, if you message me "Task 2025," we’ll give you this paper and the GPT that takes you through the "step into focus" routine—is specifically designed for this network. One of the biggest problems I have is getting people to start it because they think they should just be "white-knuckling" it. People feel like their brain should work like everyone else's and that they are just a "bad person." These papers really help to change that narrative.
William Curb: Yeah. I remember in college, I would go to the library to try and force myself to get through whatever I was working on. I’d tell myself I’d stay for eight hours and it didn’t matter how long it took, I’d just get through the reading. That was such a bad strategy. Especially with this kind of paper, it shows you needed to do something different with your brain to get it to activate in the ways that you wanted it to.
Skye Waterson: Exactly. There are a few things we need to do. I think the best way to describe it is that it's not an automatic switch; it's more like a clunky old dial that we have to hand-crank to actually get into the zone of doing work. The fact that they found this relationship allows them to use the word "causal." They have a lot more ability to make those statements because of the placebo-controlled, randomized nature of the study. It gives us the ability to feel confident saying, "Hey, I work differently and I need different things." I might need more stimulation while I’m working, or less, to help me because my networks aren’t just going to turn off and on automatically.
William Curb: Yeah, I’ve got my fidget here. Whatever I’m on, I have to have something to do with my hands because they need that little bit of extra stimulation. I think the opposite is also true: when we’re trying to relax, we also need a little bit of stimulation to deal with the task positive network part of things. Like watching TV while having a fidget so I’m not constantly going on my phone. If I'm scrolling, I'm not paying attention to the TV, I'm not paying attention to my phone, and I'm not having a good time.
Skye Waterson: That's so true. I've worked with a lot of clients where they’ve ended up taking up knitting or something similar because they need something to do. This comes up a lot with family; people feel bad because they want to spend time with their family and be present, especially during the holidays, but they actually need higher stimulation than just staring at a child playing a game. Maybe we should put some music in the background—just little shifts you can do.
William Curb: Or if you're dealing with an ADHD child and you're trying to play a board game and they're getting up and leaving, maybe they just need a fidget with them to help focus them on what is present.
Skye Waterson: Yeah, and it’s nice that when we have these conversations, we can say that the reason we’re suggesting this is because of papers showing this stuff. Even if they're researching for medication, having the papers show the brain differences is something I can’t get enough of.
William Curb: Absolutely. It’s one thing to understand that your ADHD brain works differently—to just say, "Oh yeah, I do things differently"—and it’s another thing to say, "Here is how it works differently." Because of that, there are specific things we can do.