Targeting Hyperactivity and Impulsivity in Adolescents: A Look at Viloxazine ER

Join Rakesh Jain, MD, MPH, clinical professor of Psychiatry at Texas Tech University and Psych Congress Steering Committee member, as he explores the role of viloxazine extended-release (ER) in targeting hyperactivity and impulsivity in adolescents with ADHD. In this episode, Dr Jain highlights the advantages of viloxazine ER as a nonstimulant with 24-hour coverage, offering consistent symptom control beyond the school day. He discusses its unique mechanism of action involving norepinephrine and serotonin modulation, its low risk for abuse, and its practical benefits for patients who struggle with stimulant adverse effects or require round-the-clock symptom management. With insights drawn from decades of clinical experience, Dr Jain makes a compelling case for considering viloxazine ER as a first-line or adjunct option in adolescent ADHD care. 

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Dr Rakesh Jain: Hello, dear colleagues. This is Rakesh Jain, and I am a clinical professor of Psychiatry at Texas Tech University School of Medicine in Permian Basin and also a very proud member of the Psych Congress Steering Committee. I'm both an adult as well as a child and adolescent psychiatrist. And I'm about to talk with you on an issue and a topic that is of great importance not just to me, but I have no doubt to you as well, as well as to our thousands of patients and their family members. 

And today, we'll talk about “Targeting Hyperactivity and Impulsivity in Adolescents: A Look at Viloxazine ER.” ER, of course, is extended release. So, the objectives are to explore viloxazine ER as a nonstimulant ADHD medication, highlighting its 24-hour coverage and the benefits of continuous symptom management for specific patient populations. 

So, let's dive right into it, shall we? And perhaps before we touch upon viloxazine, we ought to touch upon the very nature of what ADHD is. As we know, ADHD is the single most common neuropsychiatric disorder of human beings. Whether they are children or adolescents or adults, this is by far the most common of all disorders. And like any other neuropsychiatric disorder, it doesn't take a break. It's not merely a disorder of school or work or playground. It really is a continuous challenge for the patient. And classically, DSM-5 defines ADHD as a cluster of 3 sets of symptoms: inattentiveness, hyperactivity, and impulsivity. 

But those of us who practice medicine know that is simply an inadequate definition and explanation of what ADHD looks like in our patients. It is definitely those 3 things. But on top of that, our patients have challenges with behavioral disruption, sleep disruption, and of course, emotional disruption. These are part and parcel of the condition. 

Now, we have been identifying and treating ADHD for decades. The first FDA-approved treatment option for ADHD—a stimulant. The second one—a stimulant. But, in the last few years, there has been a real emergence of the appreciation of the challenges and the limitations with stimulants. And, as a result, nonstimulants have also arrived as added tools for our utilization to help our patients, either as first line, sometimes as a replacement for first line, sometimes even in augmentation situations. And because of the need for coverage of symptoms around the clock as much as possible—and also, perhaps because appreciating that stimulants are far less than optimum treatment options in many patients, perhaps as many as 50% of patients—is the reason why nonstimulants were born. 

And the latest one that I would love to discuss with you in greater detail, of course, is viloxazine extended-release. You might be wondering, what is it? What is the FDA indication? What is the mechanism of action? I think we should talk about those things before we dive into talking about those specific items and the objectives that I had laid out for you. 

Well, it certainly is a medication approved by the FDA for the treatment of individuals who are 6 and older with any type of ADHD. So, even though today we'll be focusing on hyperactivity and impulsivity, it’s very important to remember that viloxazine has indeed demonstrated its abilities in reducing the entirety of the symptoms of ADHD—that being inattentiveness, hyperactivity, and impulsivity—in a wide range of patients, a wide range of ages, all the way from 6 on up. That's the first thing to keep in mind. 

Perhaps the second thing to keep in mind is that its mechanism of action is highly differentiated. It truly is. It's not just a norepinephrine reuptake inhibitor. It also has direct activity on a number of important members of the serotonergic family. It definitely is not a stimulant and therefore does not carry with it a scheduling from the Drug Enforcement Agency. That is, of course, a significant plus, is it not? Therefore, the practicality of using viloxazine ER in our practices is enormous. We don't have to worry about the scheduling aspects. It can be called into a pharmacy. Worries about diversion are minimum. You get the picture, don't you? There's significant benefits there. 

Now, why are we focusing on hyperactivity and impulsivity? And the reason for that, of course, is they are really a card-carrying member of the symptomatology our patients experience, and they can be incredibly impairing. Think about it for a second. Think of all the children and adolescents and adults you have seen with the diagnosis of ADHD where overactivity, the inability to control motoric action, can lead to a lot of problems, even in adults. That can lead to difficulties both at home and at work. Hyperactivity is not to be trifled with. It is not something to just create New Yorker cartoons over. It's a real, significant impairment, as is the impulsivity. Impulsivity, of course, is an individual really knowing better but being unable to stop their responses to a stimuli. So, impulsivity could be in behavior. It could be in money spending. It could be in sexual behavior. It could be in doing things out of turn. And, culture does not forgive those things. There are real consequences to the individual when impulsivity, along with hyperactivity, is a cardinal set of symptoms for the patient to have to deal with. We should also remember these symptoms impair not just our patients, but our patients’ family members, our patients’ educational background, occupational background. Even raising your own children becomes a real challenge when an individual is deeply affected by excess hyperactivity and impulsivity. 

So, coming back to our objectives, we should first explore viloxazine extended-release as a nonstimulant ADHD medication. What does that mean? Why should we care about it? What are the positive and negative consequences of that? Let's dive into it. So, a stimulant medication by DEA and FDA definition is something that perhaps increases release of a neurotransmitter right at the synaptic cleft, almost always norepinephrine and dopamine. That is thought to create quick action. But that is also the reason why in most patients, once the medication leaves, so do the benefits. So, on a stimulant, a patient is very beholden to and tied down to the half-life of the medication. That's a real challenge, because as we have established already, the nature of ADHD is not to be just an 8- to 5- or 8- to 3-o’clock disorder. 

On top of that, many patients on stimulants, as I've said before, tend to have rate-limiting and challenging side effects. Many people live with them because they feel they have no option. But with viloxazine ER, it is a nonstimulant. I've already alluded to its mechanism of action. Nowhere do we have any evidence that viloxazine ER would carry an addiction or diversion potential. And therein lies the reason why the FDA is calling it a nonstimulant. The medical field calls it a nonstimulant. And, of course, the DEA, the Drug Enforcement Agency, chose not to apply a specific labeling in terms of categories of stimulant medications. We simply don't have a scheduling from them. 

So, that's established now, right? We now move on to discussing the need for 24-hour coverage of symptoms. Now, this again, you might say, “But we've known this for a long time.” And you're entirely correct. We've known for a long time. This is one of the most chronic of all disorders we see. It also is one of those disorders that starts very early in life. And by now, in 2025, we have woken up to the realization most individuals who have ADHD as youngsters don't lose the disorder. Hopefully, they adapt to it. But even that, the presence of adaptation to the ADHD symptoms is not guaranteed. 

In fact, let me share with you a worrisome statistic: 50%+ individuals who in their adolescence have ADHD continue to have it in their adult years. And this applies to both men and women. Now, female patients may have less hyperactivity, but you know what? Impulsivity can really dramatically damage the lives of our male and female—but I want to really focus on the female—patient quite dramatically. And the consequences can be lower self-esteem, lower self-confidence, higher rates of depression, higher rates of anxiety, higher rates of insomnia. And you know what's interesting? Even higher rates of obesity. 

So, covering a patient's symptoms 24 hours a day is not a “good” thing to have, but I would say it's a necessity. We should not allow ourselves to be seduced into thinking just because a patient is reporting majority of the symptoms between, say, the hours of 8 and 5, that's all the individual needs. Twenty-four-hour disorders need 24-hour coverage. There, I’ve said it. And, of course, I have a great deal of confidence that you really do agree with me. One of the advantages of nonstimulant medication does tend to be its ability to cover symptoms chronically, continuously through multiple hours. There doesn't appear to be, in the vast majority of patients, an abrupt kick in or an abrupt kick out. That's just because of how the mechanism of action of nonstimulants like viloxazine extended-release is. 

This is in sharp contrast to stimulants, who, by the way, do definitely have the advantage of exerting their therapeutic benefits much earlier. It's not at all unusual for a patient to have taken their medication for a few days or even a week and say, "Oh my gosh, I can absolutely tell the difference." But on the flip side, they're also able to tell you, "Oh my gosh, my medication fades out at 2 o’clock or 3 o’clock or 4 o’clock, and I need another booster dose. And if I take it, then I have trouble with appetite or sleep or rebound irritability. It's hard. It's quite hard in many patients—not all, thank God—but in many patients who take stimulants to thread that needle. That is so much easier to do with a nonstimulant medication, because the awareness that ADHD is a 24-hour disorder and it needs 24-hour coverage of symptoms is by now pretty much accepted wisdom in our field. 

So, what specific population should we be thinking about when it comes to this need for 24-hour coverage of symptoms? And maybe I should flip that question and ponder, who is that one person who simply doesn't need long coverage of symptoms of their ADHD, even though neurobiologically it seems implausible that they only have a disorder for a few hours a day? You see, don't you, that the case to be made for the use of nonstimulant is strong. 

Now, we should also acknowledge that the effect size we get from the use of nonstimulants tends not to match up to the effect size of stimulants. And that is—there is no problem with that. We just have to appreciate that these are very different medications, different abilities and disabilities. And we ought to be quite judicious in our thinking about how to comfortably reduce the symptoms of our patients. But I would like to remind you at this juncture that hyperactivity and impulsivity cause a profound amount of damage in our patients all the way from 6 to 60 and beyond. 

So, engage in this thought experiment with me, will you? So, let's just, for a second, think about a 14-year-old girl, shall we? And look, she's in school, and between the hours of 8 and 4, she's got a lot of adult supervision. She also has a lot of structure. So, you can imagine hyperactivity and impulsivity in a controlled environment with structure and the presence of adults. One hopes the damage caused by challenging levels of hyperactivity and impulsivity are modulated. The damage is not much. But please do this. Think about this very same patient. But think about her from the time when she wakes up at 6:30 before she goes and gets to school at 8 o’clock. Look at all the things she has to do. She has to wake up. She has to make sure she's organized enough to go to school. She has to interact with her family. She has to find some kind of transportation to get to the school. All of these are opportunities for untreated hyperactivity and impulsivity to cause her a lot of damage. 

Now, the same patient. She leaves school at 4. Now, she has to go to band practice. Then, she has to come home, get dinner, interact with her family, interact with her siblings, interact with social media, with her friends. And think about her on weekends, where the structure is even less. You can imagine, can't you, that some of the very hours in the day where our stimulants do not cover our patients, even the best of circumstances—well, those are the hours that our patients, when they don't have adequate coverage or symptoms, get into a lot of difficulty, a lot of friction with society. Perhaps this explains why rates of unintended pregnancy are much higher in untreated or inadequately treated individuals with ADHD. This is the reason why accident rates in teenagers and young adults are higher. And many of these accidents happen first thing in the morning when they're getting to work or afternoons or evenings or even nights. I think I'm hopefully making a pretty persuasive case to you that as much as it's possible, offering patients longer symptom coverage is ideal. 

We should also not deny the obvious fact that diversion of medications in adolescents and young adults has become very common. But we should also be mindful that in our younger patients where growth, gaining weight, and gaining height are major needs. They really are. Well, stimulants can, of course, impact that because of their significant impact on appetite reduction in certain group of patients. 

So, let's collect our thoughts here. Are we saying that nonstimulants replace stimulants? No, we are emphatically not saying that. Stimulants are wonderful medications. We should continue utilizing them. But, by the same token, practicing honesty, real honesty. And appreciating that there are a large number of patients who simply do not get the ideal ratio of efficacy to tolerability, particularly in things like hyperactivity and impulsivity. Their needs should not be ignored, especially because so many of our patients tend to have comorbidities, behavioral disruptions, mood difficulties, anxiety difficulties, sleep difficulties. In these situations, stimulants can, in fact, be a net negative. We must think about nonstimulants such as viloxazine ER as a treatment option both at the very outset—so, if we have a patient who's brand new to us, just brand-new diagnosed, I do not think we should reflexively offer them only one class or the other. I think we should have a deep conversation with the patient and the family about the positives and negatives of both classes of medications. I think with viloxazine we really ought to have a deep conversation about the data in terms of efficacy, onset of action, its ability to control multiple symptoms in multiple age groups, as well as its emerging data on executive dysfunction. All of that should be discussed. 

But, in my very final comments, I would say it's so important to appreciate that nonstimulants are here to help us. Generally speaking, our field tends to underutilize them, and that's not appropriate for our patients. We should utilize them appropriately, right? They could be first-line treatments. They could also be alternatively used in patients who have failed, who have failed, not responded adequately to a stimulant. That is a valid option, too. But the overall theme to this conversation is to appreciate that we really should focus on the 24-hour coverage needs of our patients and the benefits of continuous symptom management. I have to say for nearly every patient population that I can possibly think of.

Well, dear colleagues, thank you so much for letting me share my thoughts over 30 years of practice, in terms of thinking about our patients with ADHD. And, more specifically, this deeper dive in the exploration of viloxazine extended-release as a nonstimulant option for the treatment of ADHD. Goodbye for now.

Rakesh Jain, MD, MPH, attended medical school at the University of Calcutta in India. He then attended graduate school at the University of Texas School of Public Health in Houston, where he was awarded a “National Institute/Center for Disease Control Competitive Traineeship”. His research thesis focused on impact of substance abuse. He graduated from the School of Public Health in 1987 with a Masters of Public Health (MPH) degree.

Dr Jain served a 3-year residency in Psychiatry at the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical School at Houston. He followed that by obtaining further specialty training, by undergoing a two-year fellowship in Child and Adolescent Psychiatry. In addition, Dr Jain completed a postdoctoral fellowship in Research Psychiatry at the University of Texas Mental Sciences Institute, in Houston. He was awarded the “National Research Service Award” for the support of this postdoctoral fellowship.