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Prodrug Therapy for ADHD
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Transcript:Theresa Cerulli, MD: Just to move the discussion along, I think there is a point that might be confusing right now to listeners. We’re meshing together some mechanism-of-action pieces here with delivery systems. Those are really 2 different categories of topics, right? When we talk about, for example, short-acting stimulants and intermediate-acting stimulants and long-acting stimulants, what changes there?
It’s the delivery system, right? We’re delivering the medication over longer periods of time, when you talk about a long-acting medication by changing, maybe, the coding. Or in the case of something like Mydayis, you’re adding a third bead to that delivery system to make that drug last longer. Mydayis has been shown in studies to be a 16-hour medication. This is probably the longest-acting stimulant that we have in terms of our PK [pharmacokinetic] data.
Then there’s mechanism of action, which is a separate category when you compare something like Intuniv [guanfacine], a nonstimulant that binds to the alpha-2A adrenergic receptor, to a medication that is a stimulant medication either acting as a reuptake inhibitor or enhancing release of norepinephrine and methylphenidate. It is important to distinguish between those 2 things.
I wanted to mention 1 of medications that sometimes takes a little while to explain to clinicians and patients alike, and that’s Vyvanse [lisdexamfetamine]. Vyvanse is the only prodrug stimulant formulation we have available. And as a prodrug, it’s actually an inert substance. In its parent molecule form, Vyvanse actually is not an active amphetamine. It’s not until it’s broken down and acted upon by an enzyme in the body that it splits that molecule for the parent molecule to then release dextroamphetamine. It becomes amphetamine in the body, but in its parent molecule Vyvanse is actually an inert substance.
What does that mean in terms of patient care? Well, patients will often describe that it feels different. It doesn’t feel like that kick, the way some stimulants can feel to them. And they appreciate that they can’t exactly tell you when it starts and stops working. Physiologically, it feels a little more subtle to patients. This is not true in everyone, but that’s an example where when you carefully look at both delivery systems and mechanisms of action, how that translates to mean something to patients.
David W. Goodman, MD: That’s a very important point. To go back to the long-acting stimulants, it’s important for clinicians to know, as Tim [Wilens] mentioned, that there are a variety of preparations. You have long-acting liquids. You have long-acting pills. You have long-acting patches. You have chewables. The way in which you take the medicine is determined by the technology that’s used in that medicine.
And you can move back and forth between a mechanized delivery system, like a mixed amphetamine salt XR, or you can go to a prodrug like Vyvanse and have different delivery systems and different PK curves. The subtleties are distinguishable by the patients. Often, when I try to get them to be on a drug, I say, “Is there anything you don’t like about this?” And their answer is, “No.”
Transcript Edited for Clarity
