Emerging Treatments for ADHD

Andrew J. Cutler, MD: There is a new investigational medication called SPN-812, which may represent a very important advancement in the treatment of ADHD [attention-deficit/hyperactivity disorder]. This is a nonstimulant that has a unique mechanism of action. It has some efficacy as a norepinephrine reuptake inhibitor, but it also binds to certain specific serotonin receptors. This is important because our other available medications to treat ADHD are all working through norepinephrine and dopamine. This medication works through serotonin, which has been a bit of a neglected neurotransmitter in the treatment of ADHD.

SPN-812 has been studied in children and adolescents from the ages of 6 to 17, and it now has 4 clinical trials—2 in children and 2 in adolescents—that demonstrate clear evidence of efficacy for the total symptoms of ADHD using the standard ADHD rating scale and a subset of symptoms of inattention and hyperactivity or impulsivity. 

One of the other qualities that makes it unique is it demonstrated efficacy as early as the first 1 to 2 weeks of treatment. Also, it has a much more straightforward dosing regimen with less complicated titration. We believe this could be an important addition to our treatment armamentarium.

Also, it’s a capsule. Its extended release. If you open the capsule, there are pellets that can be sprinkled on foods like applesauce or yogurt. For those patients who can’t or prefer not to swallow pills, this is the first nonstimulant to have that property.

The safety database has been very impressive. It has been very well tolerated. The most common adverse effects seen were fatigue and nausea. It didn’t cause much in the way of insomnia or decreased appetite. It didn’t seem to cause a lot of irritability, agitation, or anxiety. As a matter of fact, it is derived from a medication called viloxazine that was approved for many years outside the United States as an antidepressant, so it might be effective in treating some of the associated comorbid conditions such as depression and anxiety.

Rakesh Jain, MD, MPH: One of the more interesting and exciting recent developments in the world of ADHD is the study of a new chemical entity called SPN-812. This is a new chemical entity for us in the United States. The study design is straightforward and elegant. It is a randomized, placebo-controlled, multicenter study of individuals who have significant ADHD symptoms. Our goal is to see, through this study, how quickly and how strongly SPN-812 affects the core symptoms of ADHD. The core symptoms are the 18 items that are part of the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, 5th edition] criteria. Of course, the scale that is most commonly used for studies is the ADHD rating scale. 

In terms of adverse effects, the medication has been well tolerated. We shall see what happens in this study, in this evaluation. On occasion, mild degrees of sleep difficulties and mild difficulties of nausea have been noted. But generally speaking, the medication has been well tolerated. Of course, phase 3 data studied in rigorous double-blind fashion tell us the full story. I excitedly look forward to seeing the final results of this study.

Andrew J. Cutler, MD: The medications for ADHD have been looked at for the possibility of disease modification. Unfortunately, we don’t have great evidence that any of them are disease modifying, although there is evidence that appropriate medication in childhood can head off some of the problems later on, such as depression, anxiety, and bipolar disorder, and may improve subsequent functioning. I don’t believe SPN-812 will necessarily be what we call disease modifying. When you stop using medications for ADHD, symptoms come right back. So we’re not necessarily curing patients. We’re managing the condition. I do believe SPN-812 has the potential to be a significant addition to our armamentarium because of this documented efficacy and safety that I mentioned.

I certainly welcome the approval and addition of SPN-812 to my clinical practice, and I see it as an option for patients for whom either a stimulant is not appropriate or contraindicated or if we have a case of parental or patient preference to not use a stimulant. This would probably be 1 of my go-to medications for that situation; or for a patients who I’ve tried a stimulant and they don’t have a good result, a good outcome from an efficacy point of view, or they have trouble with tolerability. One of the big tolerability problems in children is anorexia, or decreased appetite and suppression in growth. I see this as a good addition for patients who have trouble swallowing pills. This would be 1 of my considerations as a go-to medication because it is a capsule that you can open and sprinkle its pellets on soft foods.

I also see this as a potential option for a patient who has ADHD with comorbidities. As I mentioned, the chemical in SPN-812, which is viloxazine, was proven to be efficacious as an antidepressant. It was actually approved for use as an antidepressant around the world. The mechanism of action predicts potential efficacy for anxiety. Also, it does not appear to have potential for worsening tics, which is another issue that can be seen with stimulants.

Transcript Edited for Clarity