Choosing Between Different ADHD Formulations

Theresa R. Cerulli, MD: Andy, you talked about nonstimulants. I want to bring it back to the patients. Thank goodness we have choices.

Andrew Cutler, MD: Absolutely.

Theresa Cerulli, MD: When I started in this field 20 years ago, we didn’t have much to offer. The evolution has been incredible. These aren’t me-too drugs. They’re different designs in a way that it feels different to the patients. I mentioned my daughter earlier. When we started, she couldn’t tolerate the stimulants that existed. She was young—early in elementary school. Thankfully, we had a nonstimulant option. It wasn’t great. When she hit middle school, it wasn’t quite doing the job on the efficacy side. She had to take a break because she couldn’t tolerate stimulants. Lo and behold, we have some newer formulations. Now she’s a senior in high school, and she’s finally able to take a stimulant.

If you take the exact same molecule—whether it’s methylphenidate or amphetamine, for example—and change the delivery system, it feels different to the patient taking it. In some cases, in sharing this personal experience, this was the difference in being able to take the medication at all. It’s worth re-exploring with patients—perhaps they’ve been afraid to take medications or tried medications and failed—to look at some of the choices we have now that might be a better fit.

Michael Feld, MD: I can tell you that in the adult world, many people come to me who were treated as kids and had bad responses to methylphenidate and short-acting mixed amphetamine. Then they try extended-release [XR] mixed amphetamine, and their mind is set that there’s no way that they want to go back there. With enough confidence and teaching, these newer medications have the same chemical, many of these adults are on meds now that they would have never tried because of their negative experience with what happened when they were kids.

Theresa R. Cerulli, MD: We’re better at screening and diagnosing the disorder and comorbidities, but we also have more options in terms of treatment choices. It’s a very rewarding time. Birgit?

Birgit H. Amann, MD, PLLC: I’d like to make a quick, simple comment that works for me in the trenches because we’ve made so much progress in the way of our treatment options. The science is that I’ve got all these different choices, but there are some differences. To help patients feel more comfortable, I remind them that the art is that I need to come up with the medicine that helps them very well—proper efficacy but also 1 they tolerate well. A lot of times patients think, “I’m going to end up on the highest dose because I have this terrible, awful ADHD [attention-deficit/hyperactivity disorder].” No, we’re going to find that sweet spot, the medication formulation that’s best for you and that you tolerate well. Because of all these options, we’re better able to do that compared with 20 years ago. For sure.

Andrew Cutler, MD: If I could elaborate a little on that. With some of the older formulations, there’s not only inter-individual variability from me to you but also intra-individual. For me, from day-to-day, and some of this is because these various formulations were PH dependent for the extended relation or transit time through the gut. There are 3 newer technologies I want to quickly highlight. One is the prodrug technology, which appears to not be PH dependent and goes farther down the gut before it’s cleaved and then released. The other is the Delexis drug delivery platform technology that Michael talked about. It’s a sophisticated technology. The medicine goes all the way through the gut until it gets to the colon, so it’s colonic absorption and not pH or transit time. The other technology that Michael referred to is 1 company that has 4 different preparations: 2 methylphenidates and 2 amphetamines. This is the LiquiXR technology, which is an ion exchange resin with microparticles that are coated. This has provided a smooth delivery system with a nice duration of action and a nice, gradual decrease—the smooth landing that we talked about.

Theresa R. Cerulli, MD: Alice, what advantages and challenges do different formulations and delivery options present for our pediatric and adult patients? Some examples are frequency of dosing and titratability. What do you think?

Alice Mao, MD: It’s an exciting time to be a psychiatrist because we have many more options for treatment for our children, adolescents, and adults with ADHD. When I graduated from medical school, after residency, there were many short-acting preparations that lasted 3, 4, 5, or 6 hours. However, then there was the development of long-acting medications. Now we have medications that can last 13 hours, and some of them up to 16 hours in a day, depending on the delivery. The mechanism of delivery is very important, and it helps us in terms of helping our patients tailor the medication regimen to the duration that they need to get their work done, as well as the work they have to do at home and in the evenings.

I’m really pleased that the delivery systems have made a huge difference. When kids are young, they often can’t swallow or aren’t willing to swallow. There are medications that really help, oral formulations. We have amphetamine as well as methylphenidate compounds that can come in a long-acting oral suspension, and that allows for a smooth, gradual delivery. What’s really nice is that medications such as Dyanavel [XR] were originally made in a liquid formulation. Now they come in a tablet. Some of the individuals who, as adolescents, had responded very well to long-acting liquid preparation of amphetamines, such as Dyanavel [XR], are saying, “I don’t want to take the liquid anymore because I’m grown up now, Dr Mao. I can swallow pills.”

What’s been really amazing is that there’s a pill with the same gradual delivery system, which allows for sustained release and allows them to get through the school day or workday. It comes in tablet form. It’s been a nice transition in terms of being able to offer the same delivery in a tablet form when they have responded well previously to the liquid. Thus, we have so many more options, and there are so many medications that can last throughout the day. If necessary, we can augment with a short-acting [medication] in the afternoon. But this is life-changing for some of these folks.

Folks often ask me why I use so much of the liquid formulation in children and adolescents. One nice thing about using a liquid formulation is that with 1 prescription you can give several doses. It allows us to give a gradual titration. For example, if a child is taking a medication like Dyanavel [XR], the oral suspension, I can target a dosage of, say, 4 mL a day. Each milliliter is equivalent to 2.5 mg, but I can have them start as low as 1 mL a day and go up to every 3 days if they’re not responding to the lower dosage up to a maximum of 4 mL a day. Of course, we have to make sure that families clearly understand the directions, but we don’t have to write several prescriptions to titrate a child up to the target dose.

I also have kids who have pretty significant appetite loss on medications, but they need the medications to focus and concentrate and do well in school. For some of those kids, the nice thing is that they can take a little higher dosage during the week when they’re attending school, then on the weekends, they can go to a lower dose because they have less structured activities. For instance, I have 1 child who takes 7 mL a day during the week. That’s the dosage he needs to get the duration, get through school, and go to band practice after school. But on the weekends, because he doesn’t have to be concentrating or studying so intensely, he can drop to a dose of 4 mL and do well. There’s nowhere else that we can have 1 prescription that gives that much flexibility in dosing. That’s really important to our families. I’m so grateful that all these formulations are available…unlike when I finished my residency and graduated from medical school.

Theresa R. Cerulli, MD: Does anyone else want to weigh in on that?

Birgit H. Amann, MD, PLLC: All these things are important for the common goal of compliance. What’s my biggest goal? I want to help them function better. We’re constantly coming back to how well someone is functioning. If they have a medication that they have to take a couple of times of day, or they have a long-acting medication but aren’t getting enough duration, then they have to add a short-acting version of the same medication. They might forget to take that or don’t want another co-pay. If it takes a long time to get to the right dose, a lot of them aren’t going to comply. Having easier-to-take options helps that.

Theresa R. Cerulli, MD: An example that comes to mind is that pediatric patients might do better with the liquids, not having to swallow tablets. Thank goodness we have amphetamine XR liquid. Put it into a real-world situation. Maybe Mom and Dad are divorced, and the liquid is going back and forth in 2 households. That may be more challenging and not quite so portable, so it’s nice that there are amphetamine XR tablets. Those are examples people don’t think about. Asking the fit in terms of not only molecule and mechanism of action but also duration of action and the person’s day-to-day life. One thing I’ll say is, “Tell me what your day is like from the time you get up in the morning until the time you put your head on the pillow at night. Walk me through your day.” I ask them to give me an example of weekday and weekend. If there’s a divorce and kids going back and forth in 2 households, so are their books, laptop, and medication—hopefully.

Andrew Cutler, MD: That’s really true. We all agree that adherence is the name of the game with our medications and that all these options could potentially improve adherence. Maybe it’s because we get a longer duration of efficacy or a smoother PK [pharmacokinetic] curve, which might translate into better tolerability, less crash and rebound, an earlier onset of action. Some of the formulations we’ve talked about lend themselves to the ability to adjust the amount of medication you give from day to day, which might translate into a different duration of action. Patients, and certainly parents, like to have that degree of control so they can tailor the medication to the needs of the day, and that helps them take the medication. We all agree that that’s really important.

Transcript edited for clarity