Novel Drug Delivery Systems in ADHD and Take-Home Messages


Drs Stephen Faraone, Theresa Cerulli, Craig Chepke, and Andrew J. Cutler discuss novel drug delivery systems and provide take-home messages when treating an adult with ADHD.

Stephen Faraone, PhD: We’re going to talk about novel treatments for ADHD. First thing we’d like to discuss are the benefits and limitations of recently approved FDA therapies with novel drug-delivery systems. Pro drugs, devices, single-pulse sustained-release medications, patches, tablets, and suspensions. What do you all think about this wide array of therapies that the FDA has approved in the last few years?

Craig Chepke, MD, FAPA: It’s great. Like I mentioned earlier, I use every single one, more or less, of the various formulations of stimulants. Any advancement is going to be a one that I welcome. And especially as a chemistry major in college, that’s what lets me really investigate the pharmacokinetics of these different formulations. And they are just so much better, recently. Like I said, an extended release from just 10, 15, 20 years ago is very primitive, compared to what’s coming out today. A lot of clinicians, when they hear that, oh, another extended-release amphetamine, another extended-release methylphenidate, it is very different. It’s like having a V-6 engine in 1969, versus a V-6 in 2022. You’re going to have a lot better parameters for this newer engine than you did for the old one.

Stephen Faraone, PhD: Andy, what’s your take-home message for these new medications? Is there one that pops out to you, that you say, “this came along, and it’s been useful in my practice?”

Andrew J. Cutler, MD: It has been very exciting, and it is very confusing, with all the new medications approved. Most of the ones that have been approved over the past few years are formulations, newer formulations of stimulants. It’s either amphetamine or methylphenidate. That’s not necessarily new. It’s this increased technology that Craig’s talking about. And I completely agree. The newer ones tend to have a lot of superior delivery mechanisms. And that translates into a superior pharmacokinetic profile. We know that, for stimulants, there’s a tight relationship between PK and PD. Meaning the pharmacokinetic profile, or what it looks like in your blood, and the clinical effect or clinical efficacy. I’m very fascinated by the fact that we finally have a prodrug version of methylphenidate available, the serdexmethylphenidate. We’ve had the lisdexamfetamine amphetamine version available for a long time. A new tablet form of an extended-release amphetamine has been just recently approved, and I’m very excited about. It has superior pharmacokinetics, and it’s made by an ion exchange, a coded particle system that’s very advanced. And Craig would understand it better than me, being a chemistry major. And then, of course, there has also recently been an amphetamine patch finally approved. For many years, we’ve had a methylphenidate patch. We now have a methylphenidate and an amphetamine version of both prodrugs and of patches. And that certainly allows us to have a tremendous ability to individualize, as Craig said. It is worth taking a couple minutes to try to familiarize yourself with these different formulations. And finally, the one we’ve all alluded to, viloxazine extended release, was approved for kids in April of this year, 2022, was now approved for adults. And that’s been a significant addition. There is one in development that’s not far away, I’d like to mention. That’s called sentinaphidine, which I’ve been very involved with developing. That’s a triple reuptake inhibitor. It’s very exciting. What we need, of course, are probably some newer mechanisms that go beyond the traditional monoamines of norepinephrine and dopamine. But that’s what keeps us going.

Stephen Faraone, PhD: Theresa, I’m going to turn it over to you, and ask you what you think about some of the new devices that are out there for ADHD.

Theresa Cerulli, MD: The more the merrier. Just allows us to individualize treatment options. It’s never about one thing being better than another. Not a drug, not a device. But like any good relationship, finding the right fit between the individual patient and their treatment needs. That’s my take-home message.

Stephen Faraone, PhD: Absolutely. In a way, it’s a gift to the practitioner that the toolbox is full of tools that can help the patient. And we now have this trigeminal nerve stimulation that Jim McGuff published a paper on. Very good RCT, randomized control trial. Very decent effect size, close to what you would expect for stimulant medication. It needs to be shown how it works in clinical practice, but it’s something people should look at. The FDA also cleared a game for ADHD, called EndeavorRx®. And what the clinician needs to know about EndeavorRX® is that its primary outcome in the clinical trial was a neuropsychological test of attention. It did a good job separating from placebo. But in the clinical trial, although it improved ADHD symptoms a lot, it didn’t separate from placebo. And until we see that happening, we can’t recommend it as a treatment for symptoms of ADHD. But I say keep your eye on this device field. Because my expectation is, in the next 10 years, we’re going to see some creative devices coming out, that are going to be very helpful for kids with ADHD.

Andrew J. Cutler, MD: Steve, there’s devices and then there’s PDTs, prescription digital therapeutics. And that game you’re talking about is a therapeutic video game that’s a prescription digital therapeutic. There are others in development. That device you mentioned from Jim McGuff’s group is interesting. And then the other area- believe it or not, TMS is also being looked at. And there are some newer protocols that appear to be even more efficient in delivering the magnetic pulses, that have some promise, as well. I agree with you. We’re going to go beyond the pills.

Stephen Faraone, PhD: That’s great.

Theresa Cerulli, MD: I will say I’m cautiously optimistic, in that there have been devices in the past. And I have been- and used clinically. What I have found is that, although you may see initial benefits- and that was supported not just clinically but by the data of some of these in the past. The sustained benefit wasn’t there. And 6 months later, a year later. Again, cautiously optimistic. I know we’ve got a long way to go before I’m convinced about the sustained benefits. But hopeful.

Andrew J. Cutler, MD: That’s one of the things that must be worked out. What is the long-term protocol? Do you do a repeat treatment every 6 months, for instance? How does that work?

Stephen Faraone, PhD: That’s right. And for the EndeavorRx® they do have a very nice protocol for long-term treatment. They have thought that through. It will become a template for the future, for how these device-type treatments will be administered. But we’re going to end on that optimistic note, that in the future we’re going to see devices that may replace our drugs, may not. We probably will see more formulations of drugs, more non-stimulants. But practitioners need to know there are a lot of new formulations, new drugs out there, that they should take a close look at. Because it provides you with another tool in the toolbox, that can help your patients with ADHD. Thanks, everybody, for participating. I really enjoyed this discussion with you today.

Transcripts edited for clarity

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