Navigating ADHD Care Forward: The Future of ADHD

In this roundtable discussion featuring a panel of experts, Dr Gregory Mattingly, Dr Richard Price, and Dr Birgit Amann focus on the evolving future of the ADHD landscape and address current unmet needs in ADHD treatment for both adult and pediatric patients. The panelists discuss the challenges faced in clinical practice, highlighting clinician and patient perspectives. This session emphasizes the current unmet needs in the overall ADHD landscape, prioritizing both clinicians' and patients' perspectives, and highlights concluding key takeaways. 

Dr Greg Mattingly: So let's close by talking about, as we think about the future of ADHD care, what are some of the unmet needs right now as we look towards the future? We think about how do we address those for clinicians out there when we try to move the needle forward for kids, adolescents, college students, adults, seniors with ADHD. Birgit, what would you say are some of the unmet needs right now as you look towards the future for our patients?

Dr Birgit Amann: Well, I would love to see more research with combined stimulant and nonstimulant use, because we are having to do that, your comparison to the benzodiazepines and the SSRIs, but with the stimulants and the nonstimulants, that's real-world. So to see more of that type of data would be helpful.

Dr Greg Mattingly: And I'll borrow from the rest of health care. We've learned in almost every disease state that targeting multiple mechanisms quite often gives you better outcomes than just targeting one mechanism, right?

Dr Birgit Amann: Mm-hmm.

Dr Greg Mattingly: So if you look at blood pressure, not many people just take a diuretic anymore. They take a diuretic plus this, plus that. Not many people with HIV take a single antiviral; they take a combination of antivirals that have multiple mechanisms. Same thing's, true with diabetes, same thing true, starting to be true with depression, where we use augmentation and adjunctive strategies to get better outcomes. We haven't talked much about that with ADHD. So I think one of the places where your literature really helps to move the needle forward is saying, in a real-world practice, does it make sense to sometimes combine? Does it make sense to think about how we start with one agent and then maybe use an agent with a different mechanism of action, complementary, maybe not at the same dose, maybe a little lower dose, to fill those unmet needs. So how would you think about, given some of the learnings from your article, how do we apply those in clinical practice about when to use combination when not to use combination?

Dr Richard Price: Right. So what came out more recently is elucidating the mechanism, potential mechanism of action of viloxazine ER. So it was initially thought to be a norepinephrine reuptake inhibitor, and it is, but it's very mild in that respect compared to atomoxetine and Strattera. It has other effects on serotonin receptors, both antagonistic, which can modulate glutamate, co-modulate serotonin prefrontal cortex. It also has partial agonist effects on serotonin, which can affect norepinephrine, dopamine, and serotonin as well. So once we understand a little bit more that this is just not another NRI, and we understand those mechanisms, then it starts to make sense how viloxazine ER can be used in the ADHD-plus population, which is what we frequently see. And perhaps not having to always use additional agents such as SSRIs for depression/anxiety. We have to remember viloxazine ER, in Europe as viloxazine 3 times a day, was marketed as an antidepressant because that was its first use.

Dr Greg Mattingly: Yeah, they had a hunch that it was helping with mood and anxiety. So that's where it cut its teeth in Europe before it came  here. So I would say an unmet need. I love the combination data. I think that is an unmet need. An unmet need is novel mechanisms.

Dr Richard Price: Yes.

Dr Birgit Amann:  Mm-hmm.

Dr Greg Mattingly: We don't need more of the same thing. I probably don't need a lot more methylphenidates and amphetamines. I got a lot of those already.

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: I need novel agents that touch the brain differently. So the patients that haven't responded to one mechanism, I have something new to offer. And I think that was your gut instinct, when you started seeing viloxazine, you said, Hey, there's something different here,

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: Different with onset, different with symptom improvement, different in these complex comorbid patients I'm taking care of. And you're right, we knew it was more than just norepinephrine, but it took a while to figure out the serotonin piece of the puzzle. Because it's not a serotonin reuptake inhibitor.

Dr Richard Price: Important.

Dr Greg Mattingly: It's not an SSRI plus…

Dr Richard Price: It’s not a dopamine reuptake inhibitor.

Dr Greg Mattingly: Yeah. So it's a norepinephrine reuptake inhibitor, which raises norepinephrine and dopamine, but it directly modulates some specific serotonin receptor subtypes.

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: And we know some of those receptor subtypes get involved with mood and anxiety, but some of those also get involved with cognition.

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: And so it's a very interesting play when you look at it. When you look at areas of the brain that we see those increase, we see that serotonin was increased in the prefrontal cortex, but it was also increased down in the nucleus accumbens, areas of the brain that get involved with reward and pleasure and modulation in a way that we haven't seen with any other ADHD treatment. So it gives us a hunch, your hunch, that there was something different going on here. So I would think about combination data as an unmet need, right? Can I use this with other things? Which your study is one of the pieces. We're doing some other studies right now looking at combination data to say, how do we combine, when do we combine, what's the benefits of combining? I think novel mechanism.

Dr Birgit Amann: Mm-hmm.

Dr Greg Mattingly: I'm a big fan that mechanisms at least gives you a reason to believe, a reason to say does this theory hold true when I start using it with patients? And you mentioned, for example, the substance use population. I think this is a really interesting compound for those people that have mood anxiety plus.

Dr Richard Price: Sure.

Dr Greg Mattingly: if you started self-medicating because they're not doing well, could this be an agent we would use there for some of those patients, right?

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: And then finally, how does this work for those complex comorbid patients?

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: Okay. So I think there's some research that needs to come out that says, listen, let's take a look and actually measure not just your global population of people that have a lot of complex things, let's take a look at people that do have mood disorders, anxiety disorders, stress-induced disorders, sleep disorders. Where do these different agents play? What's the role of viloxazine in that complex group? I think our gut feeling is, it's got a role there, right?

Dr Richard Price: Well, I know it does from my clinical experience, haven't taken the time to put the data together yet. But there were a couple studies that came out this year, which were very interesting. One was ADHD and Alzheimer's.

Dr Greg Mattingly: Yep.

Dr Richard Price: You know that study? Having ADHD was predictive of Alzheimer's, and treating ADHD might favorably impact on Alzheimer's. So I'm thinking about treating my Alzheimer's patients with ADHD meds. I'm thinking about a nonstimulant, but I don't want to cause orthostasis. I don't want to cause falls. I'm using this agent in that population. I'm seeing cognitive benefits. Another interesting study came out this year was ADHD and borderline personality disorder and impulsivity and self-harm, and how treating the ADHD aggressively in borderline personality disorder can favorably impact on the borderline personality disorder if there's other symptoms. So having something that lasts throughout the day, has mood enhancing effects, has anti-anxiety effects, impulsivity effects, and cognitive, executive functioning, planning, using your wise mind over your emotional mind, getting a lot of success in the borderline population as well. So anxiety, depression, borderline, Alzheimer's, substance abuse. We've been using Wellbutrin, very unappealing to people who've been used to high doses of amphetamines, methamphetamines, and other prescribed non-prescribed stimulants. Putting this in fits the depression, anxiety, lasts all day, cuts craving. So I'm seeing this empirically. Haven't taken the time to written all this up yet, but I see a huge role for ADHD plus and viloxazine ER being your go-to.

Dr Greg Mattingly: Yeah, that’s really interesting. There's a couple of really important concepts that you're kind of touching on. We know that mental health conditions when untreated, let's use depression, bipolar, schizophrenia, untreated mental health conditions are damaging to your DNA and also damaging to neural connectivity in the brain. So nerve cells and neural networks become less connected, which makes you less resilient under stress. So untreated depression, untreated schizophrenia, untreated bipolar, damages neural connectivity, which makes you less resilient. We just had an article come out in the last several years from colleagues in Spain that looked at untreated ADHD, and untreated ADHD damaged neural connectivity as well. So an untreated mental health condition where I'm not doing well damaged neural connectivity, which we know has puts you at increased risk of developing secondary mental health comorbidities and decompensating under stress. So I think that's a really important message about the importance of ongoing holistic treatment, not just to feel good in the now, but to feel good in the future, right?

There was another study that just came out this summer, and it touches on something we've all talked about, and it was ADHD untreated was increasing your genetic risk, epigenetically of Alzheimer's disease, higher genetic aging. And so it’s really fascinating not just then to the brain, but your DNA itself causing an increased genetic aging burden with untreated ADHD. One of our topics this year at APSARD, if everybody can hopefully come join us down in Orlando or tune into some of the information we'll be discussing, we're going to talk about ADHD in seniors. And how does ADHD increase the risk of other health conditions as you age?

Dr Richard Price: Mm-hmm.

Dr Greg Mattingly: So what does ADHD by itself do? And then how does ADHD increase your risk of those other health conditions associated with aging?

Dr Richard Price: And how many geriatricians are screening their patients for ADHD?

Dr Birgit Amann: Mm-hmm.

Dr Richard Price: That's a childhood thing.

Dr Greg Mattingly: Correct.

Dr Richard Price. Ask the questions.

Dr Greg Mattingly: Yeah.

Dr Richard Price: Ask the questions.

Dr Greg Mattingly: We did a study, and David Goodman and some of our colleagues did a study looking at memory in aging clinics. So I come in and I'm 60 and I'm having memory issues, focus issues. They're screening for Parkinson’s, Alzheimer’s, whatever. Less than 1 in 5 even had ADHD on their radar screen as a potential cause of cognitive issues in people that were 60+. So saying, listen, it's not just a childhood disorder, it's a life disorder for many of our patients, untreated ADHD becomes complicated ADHD with comorbidities. It's damaging neural networks, which damages resilience. So I'm less resilient under stress, and I'm increasing both my neurologic and my genetic burden of picking up other geriatric illnesses as I age. So I think it's a fascinating world right now. We're always learning what we don't know, but it makes us want to go out and do the things you've been doing about saying, where can I research these things to find answers for the future? Any other parting thoughts for our audience out there, Birgit? As you think about our journey today here over the last couple hours talking about this topic, what are some of the hopeful messages when it comes to treating ADHD and what you see in the future?

Dr Birgit Amann: I think it's just about recognizing that we have very good medication options for our patients and we need to use them properly, appropriately, dose them properly. If we treat them adequately, it gives them hope. It just makes a huge impact on their lives. So working together to find that right medication and other treatments is critical, but we have access to them. Medications like viloxazine can make a huge difference for them.

Dr Greg Mattingly: Okay. Looking to the future, hopeful thoughts for ADHD, what are some of the things we need to think about? What are some of the unmet needs and what's your hope and aspiration for the future?

Dr Richard Price: So my motivation is solely for the welfare of the patients and for the welfare of society. And it doesn't matter how we get to that goal, as long as it's done safely and effectively and quickly. And I think that viloxazine ER, it's like the best kept secret. People don't know about it. They don't appreciate what it can do. Just add to your point about mechanism, it may even have some anti-inflammatory effects that we're beginning to understand and how that impacts on the brain. So I feel that not just in ADHD, because we can't think just categorically anymore about psychiatry. We have to think holistically and dimensionality, executive functioning and mood regulation and anxiety conditions, they often all overlap with one another. And if we can identify an agent with a unique mechanism of action that can, parsimonious way, monotherapy, address many of these things as a new foundational treatment, your first two, your go-to, your first-line treatment, and then we might have ancillary treatments on top.

It's a very safe option. And I think the word needs to get out. And my dream, my vision is that within the next few years, we'll start seeing this reversal. And I think that will be a very impactful public health initiative. And it will help with many other liabilities that come from stimulants that we're facing right now, particularly in the youth. And perhaps forums like this. Get out to TikTok, people discover it and they say, Hey, wait a minute. There's something else out of here. And I'd say, give me 2 weeks and I'll show you the world.

Dr Greg Mattingly: Give me 2 weeks.

Dr Richard Price: And I'll show you the world.

Dr Greg Mattingly: Yeah. So my hopeful message when it comes to ADHD is breaking down barriers and breaking down stigma. When I first started doing this 30 years ago, there were a lot of stigma to ADHD. It wasn't something that we were always taught about in residency. It was maybe put off to the side as a different type of condition, and maybe in patients that had ADHD coming in for help with something that they felt a little shame, a little guilt about. So I think breaking down those barriers, breaking down that stigma, is really a hopeful message for the future. That's led to, I think for all of us, the reason we're ADHD advocates, that if anything we do in mental health care, I think this is one of the places where we make the biggest difference in the lives of our patients.

Dr Birgit Amann: Mm-hmm.

Dr Greg Mattingly: So being a part of their journey. So I think it's a hopeful message. It's an area where we're learning more all the time. And I would say that viloxazine is a step forward, it's maybe a paradigm shift about how we reset our expectations, but there's other agents in development. So it's the first of a new future when we look at these futures for the treatments of our patients.

I want to thank the audience out there for joining us for this roundtable. I want to thank my colleagues for coming here with us – friends, colleagues, researchers, most importantly clinicians who care. So thank you for coming here and sharing this time with us.

Dr Birgit Amann: Thank you.

Dr Richard Price: Thank you.