Advances in the Management of ADHD in Adult Population - Episode 13
Greg Mattingly, MD, and David W. Goodman, MD, discuss the recent approval of viloxazine in children and its clinical profile in the pediatric and adult populations in ADHD.
Theresa R. Cerulli, MD: Dr Mattingly, you were involved in a lot of the trials. I’d love to hear your thoughts on emerging treatment options in ADHD [attention-deficit/hyperactivity disorder]. Can you discuss the recent approval of the noradrenergic reuptake inhibitor, for example, viloxazine? You mentioned this earlier, but let’s hear more about its multimodal mechanism of action and clinical profile.
Greg Mattingly, MD: Certainly. I’ve been involved in ADHD research for about 30 years with a lot of my colleagues. David and I have known each other for over that span. We’ve developed a lot of different stimulant preparations, but the holy grail has been a nonstimulant that offers something different. There’s a product approved for children adolescents called viloxazine extended release. It modulates the norepinephrine receptor, which our other nonstimulants do.
If you go back to some of the pivotal trials, some of the pivotal understanding, it does some unique things. It raises serotonin. It raises dopamine. We see in specific areas of the brain that viloxazine is raising not only norepinephrine but also dopamine and serotonin in the prefrontal cortex. We see robust elevation of all of those. If we go down to some of the areas of the brain that get involved with addiction and a tendency to want to take something more than I should, we see that viloxazine is very sparing with not having as much dopamine properties.
In the studies with the viloxazine, the first thing we saw was there was no habituation—we didn’t build a tolerance to it. If you stopped cold turkey or ran out of it, there were no withdrawal adverse effects associated with it having been in those trials—no habituation, no tolerance, no craving, no withdrawal. We started saying, “What’s the right dose of this medicine that has a multimodal mechanism?” It’s hitting the brain through multiple pathways, so what’s the right dose? In the pediatric studies, the dose range is 100 to 400 mg. The starting dose for kids ages 6 to 12 years old is 100 mg. The starting dose for adolescents is 200 mg, and most kids are going to take between 200 and 400 mg. Very few wind up 100 mg in the long run.
In those studies, a few things offer us some hope. We found that in the pediatric data, most children started improving on the medicine after the first week. You didn’t have to wait a month the way many of our medicines are taken. Within the first week, parents and kids said, “I’m doing better.” Clinicians said the kids were doing better. In adolescents, that’s a little harder place to move the needle. There tends to be more going on in a teenager’s life. But even there, we saw that improvement started within the second week of treatment. One long-term study that we were a part of—somebody referenced it earlier—from that pediatric population said if you stay on the medicine, open label, and come back to the clinic, let’s measure you over of a year. On average, a kid on viloxazine didn’t have a little improvement in their ADHD. They had dramatic improvement in their ADHD symptoms.
Their symptoms were down to what we call minimal or less on average. Parents were rating their kids as doing better. Kids would come in and tell me they were doing better. Is it going to work for everybody? Absolutely not. But it’s giving us a tool approved in children that, with long-term use, we saw significant efficacy. I’ve been a part of adult ADHD trials. This isn’t FDA approved for adults, but those data are sitting in front of the FDA. The trial results were positive. Hopefully, we’ll soon have another option for adults with ADHD.
David W. Goodman, MD: It’s interesting, Greg. The profile on viloxazine to me suggest a number of things. One is we talk about ADHD as a dopamine disorder. That’s like describing the Mona Lisa as a picture of a woman. It doesn’t begin to explain the complexity of the neuroscience. When you say that dopamine goes up if I give this drug, I will then ask, “In what area of the brain are you talking about?” From the viloxazine profiles, you can see that dopamine will increase in some areas and not in others. You’ll see that serotonin goes up in some areas and not in others. The complexity of ADHD is far beyond the reductionistic neuroscience we talk about in regard to this as a dopamine disorder. Every medication we give that’s going to be effective should be a dopamine agent.
Transcript Edited for Clarity