On April 2, 2021, viloxazine, brand name Qelbree, received FDA approval for the treatment of ADHD in children and adolescents ages 6-17 years old. The latest issue of The Carlat Child Psychiatry Report includes a News of Note covering this newly approved medication for ADHD. In this podcast, we discuss the advantages and disadvantages of viloxazine for children and adolescents with ADHD.
Published On: 6/21/2021
Duration: 11 minutes, 55 seconds
Related Article: "Viloxazine (Qelbree): A Faster Strattera?", The Carlat Child Psychiatry Report, April/May/June 2021
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Dr. Feder: On April 2nd, 2021, viloxazine, brand name Qelbree, received FDA approval for the treatment of ADHD in children and adolescents ages 6-17 years old. The latest issue of The Carlat Child Psychiatry Report includes a News of Note covering this newly approved medication for ADHD. In this podcast, Mara and I will discuss the advantages and disadvantages of viloxazine for children and adolescents with ADHD.
Welcome to The Carlat Psychiatry Podcast.
This is another episode from the child psychiatry team.
I’m Dr. Josh Feder, The Editor-in-Chief of The Carlat Child Psychiatry Report and co-author of The Child Medication Fact Book for Psychiatric Practice.
Mara: And I’m Mara Goverman, a Licensed Clinical Social Worker in Southern California with a private practice. So, Dr. Feder, what is viloxazine and how does it work?
Dr. Feder: Viloxazine is a norepinephrine reuptake inhibitor, similar to atomoxetine (Strattera), which was approved in 2008. Viloxazine has been studied for various indications since the 1970s. It originally received an FDA orphan drug designation, which is a less rigorous testing process than the process for drug approval, for narcolepsy and was studied for nocturnal enuresis and depression, though it did not gain approval for either indication.
Mara: Viloxazine is supplied in dosages of 100, 150, and 200 mg extended-release capsules. It takes 2 days for this preparation to reach steady-state blood levels, and there is a ~10% reduction in absorption if viloxazine is taken with a high-fat meal or if the capsules are opened and sprinkled on applesauce.
Dr. Feder: The recommended dosage for children 6–11 years old is 100 mg once daily, titrated as needed weekly by 100 mg increments to a maximum of 400 mg. For 12- to 17-year-olds, the starting dosage is 200 mg and can be titrated weekly in 100 mg increments up to 400 mg.
Mara: The pharmaceutical company that manufactures Qelbree has not yet released the price of their newly approved ADHD medication, but they claim that its price will be competitive with other ADHD medications. So, what’s the evidence supporting the use of viloxazine in ADHD?
Dr. Feder: In their Phase III studies of viloxazine in ADHD, Supernus Pharmaceuticals performed four short-term, six- to eight-week randomized controlled trials. 1,013 children and adolescents (ages 6–17) were randomly assigned to various doses of viloxazine (100–600 mg per day) or placebo.
Mara: The outcome measures included the ADHD Rating Scale-5 (ADHDRS-5), which assessed symptom severity, and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) to assess functional impairment.
Dr. Feder: In one of the studies, patients taking viloxazine 400 mg daily improved significantly more than those assigned to placebo; however, the 600 mg dose did not reach statistical significance.
Mara: Yeah, but what about its magnitude of effect? Can you tell me about viloxazine’s effect size in ADHD?
Dr. Feder: Of course. In the Phase IIb double-blinded, placebo-controlled trial of viloxazine, researchers randomized 222 children, ages 6-12, with ADHD to receive either a placebo or 100, 200, 300, or 400 mg of viloxazine per day. They found that the groups randomized to 200, 300, and 400 mg doses of viloxazine achieved significant improvements in ADHD Rating Scale-IV scores versus placebo. Based on the change in ADHD Rating Scale-IV scores the 200 mg dose had an effect size of 0.547, the 300 mg dose had an effect size of 0.596, and the 400 mg dose had an effect size of 0.623.
Regardless, we will have a better understanding of viloxazine’s effect size in ADHD after more RCTs evaluating its efficacy have been conducted. More studies will allow us to perform meta-analyses of viloxazine in youth with ADHD, which can provide us with a more substantiated effect size of its efficacy in ADHD. Not to mention, non-industry funded studies of viloxazine should be conducted so that we can be more certain of what viloxazine’s effect size in youth with ADHD really is.
Mara: So, what about its speed of response?
Dr. Feder: In one study, patients assigned to viloxazine 400 mg began to show improvement over placebo by week 1—more quickly than most studies of atomoxetine, which generally separates from placebo around week 3.
Mara: Okay, but here’s the million dollar question. Is viloxazine more effective than atomoxetine and other stimulant medications for ADHD?
Dr. Feder: Well, viloxazine has not been compared head-to-head with stimulants or with atomoxetine, so its comparative efficacy is unknown, but it’s clearly slower than stimulants, with a clinically meaningful onset similar to atomoxetine beginning at 2–4 weeks.
Mara: And the preliminary data reported in press releases show that viloxazine may work a little bit faster than atomoxetine. But there’s no reason to expect it to be any more effective in the long run, nor do we expect it to compare favorably to stimulants.
Dr. Feder: The reason why we don’t expect viloxazine to be more effective than stimulants is because atomoxetine is generally less effective, with response rates only about 50%–75% of typical stimulants. Also, studies have shown that the effect sizes of stimulant medications are significantly greater than that of atomoxetine in ADHD.
Mara: As a side note, the viloxazine studies have been criticized for how they analyzed their research data.
Dr. Feder: Yeah, the researchers of the Phase III trial completed the study then used a crossover mapping from the original outcome scales—the ADHD-RS-5 and WFIRS-P—to the Clinical Global Impression Scale. Such “post hoc” analyses often find positive results that may not be valid.
Mara: Now let’s cover viloxazine’s side effects and safety.
Dr. Feder: In the recent Phase III trial, viloxazine’s side effects, like other norepinephrine reuptake inhibitors, included sedation, mania, increased blood pressure and heart rate, and suicidal ideation.
Mara: Six out of the 1,013 patients reported suicidal ideation, 1 reported suicidal behavior, and 2 patients reported both suicidal ideation and behavior for a total of 9 patients, which is 0.9% of the total sample.
Dr. Feder: Two control patients reported suicidal ideation (0.4%), though there were no completed suicides in either group.
Mara: Irritability and insomnia were more common in the viloxazine group, with 4% reporting insomnia (vs 1% in placebo) and 3% reporting irritability (1% in placebo).
Dr. Feder: Viloxazine is a potent inhibitor of CYP1A2 and is contraindicated with duloxetine, ramelteon, tasimelteon, tizanidine, and theophylline.
Mara: To recap, viloxazine is the second norepinephrine reuptake inhibitor to be approved for ADHD. It’s not clear if it has any advantage over atomoxetine, or any of the stimulant medications, though if its reputed faster onset of action is better substantiated, it may be an advantageous treatment option.
Dr. Feder: As with atomoxetine, you should monitor patients for suicidality, mania, and drug interactions. And as more research comes out on viloxazine, we will get a better idea of how it stacks up against atomoxetine and other stimulant medications for children and adolescents with ADHD.
Dr. Feder: The News of Note piece on viloxazine is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully people check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits.
Mara: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry.
Dr. Feder: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us to bring you unbiased information you can trust.
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