Managing Pediatric ADHD with Viloxazine

Theresa R. Cerulli, MD: Viloxazine is a really exciting, I’m going to say NCE, new chemical entity, as the FDA has categorized it. It’s a novel agent that is a serotonin-norepinephrine modulating agent. Those are my words, not the FDA’s, but the FDA calls it an NCE. Viloxazine has been available and prescribed in Europe for many years as an antidepressant, so it has an interesting history. In the United States viloxazine has been FDA-approved for treating ADHD [attention-deficit/hyperactivity disorder] as a nonstimulant. We haven’t had many nonstimulants; we now have one as of April 2020. Qelbree [viloxazine] has been approved in children and adolescents in the US [United States] for treating ADHD.

What does that mean to have a serotonin-norepinephrine modulating agent, and why did I say this is exciting for us? Well, I mentioned that it was approved in Europe for many years as an antidepressant, so it already tells you there’s something different about this particular drug. Even though in the United States, it’s approved for ADHD, one might look at its mechanism of action to understand better how this may be different as an NCE, new chemical entity. The science behind it, if you look at the pharmacodynamic data and what happens in terms of neurotransmitter shifts for the folks exposed to viloxazine, in the prefrontal cortex, you’ll see elevations in dopamine, norepinephrine, and serotonin. That’s what we mean by a modulating agent of these neurotransmitters. All 3 neurotransmitters that we know have been involved in treating many different conditions in psychiatry over the years—dopamine, norepinephrine, and serotonin—all levels are elevated in the prefrontal cortex.

Historically, when we worry about substance abuse, we worry about levels of dopamine increasing in areas of the brain involved in the reward pathways and the risk of things, whether it’s a gambling addiction or substance addiction or obsessiveness, there’s a rewards pathway in the brain. That’s not the prefrontal cortex. The good news is elevations of dopamine in the prefrontal cortex help with focus and concentration and don’t have the risk of substance abuse. With a nonstimulant like viloxazine, we don’t run the risk of abuse and dependence. There’s no black box warning. It’s why it’s classified as a nonstimulant, and with the neurotransmitter shifts I just described, this really lends itself nicely to looking at the folks with ADHD and comorbid conditions who otherwise might have not done well on a stimulant, and even had the comorbid condition exacerbated by stimulant intervention, in addition to the risk of abuse and dependence. So it’s very exciting. We have not had many options as nonstimulant medications over the years, and we have never had a nonstimulant option that elevates dopamine, norepinephrine, and serotonin in the prefrontal cortex.

For me, when I picture where to integrate viloxazine into my practice, as of now it’s FDA approved for children and adolescents up to age 17. That’s the first patient population I’m looking to. In children and adolescents who do have comorbid conditions, my thought is moving Qelbree, or viloxazine, to more of a first-line agent. That’s because of the pharmacodynamics of this drug. When we talk about viloxazine and elevations of neurotransmitters, where it binds in the brain and the shifts, that’s pharmacokinetics and pharmacodynamics. How do I translate that to clinical practice? It speaks to those patients who need to have those neurotransmitters impacted. It’s instead of an approach that we’ve used previously of a stimulant plus an SSRI [selective serotonin reuptake inhibitor], a stimulant plus an SNRI [serotonin and norepinephrine reuptake inhibitor], a stimulant plus a mood stabilizer. If you have a medication that can in and of itself cause neurotransmitter shifts in all 3 of the neurotransmitters that we’re talking about involved in the comorbidities and the ADHD itself, we may be able with monotherapy to treat this child and adolescent, both the ADHD and the comorbidities, just as we’ve been talking about. The push from the SDBP [Society for Developmental & Behavioral Pediatrics] and the American Academy of Pediatrics is to be able to both diagnose the comorbidity and make sure that we are properly treating the comorbidities in addition to treating the core symptoms of ADHD.

Transcript edited for clarity.