Long-Acting Stimulants for ADHD


Transcript: Theresa Cerulli, MD: Thanks, Ann, for your nice summary on the short- and intermediate-acting stimulant medications that we have available. There has really been an incredible change over the years, since I started in this field 20 years ago. We have so many more options.

David, how about the long-acting stimulant preparations? What else is out there?

David W. Goodman, MD: Well, talking about options, at last count there were 28 different preparations of stimulants available. And so this becomes a very confusing quagmire for clinicians to sort out which medication they should use. So let me sort this out.

There are 28 different preparations, which breaks down into 4 chemical compounds. You have methylphenidate and dexmethylphenidate, which are 2. And amphetamine, which is racemic or a dextroamphetamine. Or you have Adderall, which is mixed salts—4 salts. We think about compounds first and then think about delivery systems.

For each of these compounds, there’s a different delivery system that will extend the duration of action. The technologies you use are various. How do you sort through which medicine you use? It’s generally recommended to start with a long-acting option, whether you want to start with a long-acting methylphenidate or a long-acting amphetamine.

I don’t know, from a patient’s profile, who is going to respond better to 1 versus the other. Based on Dr Sam Cortese’s meta-analysis of 144 studies, research would seem to suggest that an amphetamine is preferential to a methylphenidate. Methylphenidates, however, may be a bit more tolerable in children compared with amphetamines. That’s group data. On an individual patient basis, I have no way of knowing who is going to respond. So the technologies are important because they give you different delivery systems and different durations of action.

They also give you a different PK [pharmacokinetic] curve. And so the duration is based on the PK curve and the delivery system. If you choose a beaded preparation of mixed amphetamine salt XR [extended release], that’s going to give you a different duration and a different PK profile than an amphetamine that’s a pro drug and not a mechanized delivery system. For clinicians, think about compound first. If the patient responds to a compound but has adverse effects, you may want to change that delivery system.

If they don’t respond to the compound, you may want to change the compound and then take a look at the delivery systems. This is very much based on clinical impression. I know Tim can speak to a lot of the research that will help differentiate this, but at the end of the day, the clinician is really left with a lot of choices. That’s great. But the more choices there are, the more confusion that occurs. We want clinicians to choose 2 or 3 options that they’re comfortable with, so that they don’t get overwhelmed and then decide it’s too complicated to treat. So Tim, I wonder if you could just elaborate on the research basis of that?

Timothy E. Wilens, MD: Well, you know, there is now more and more research about how quickly the PK curve changes and how people respond to that, and also the dissolution curves. There’s certainly work that shows that, for example, not all extended releases are exactly the same, and they have different profiles. The analog classroom model that Ann and others have been involved in have actually helped ferret that out—important differences.

Another thing I would say that helps differentiate some of the extended release, at least in kids, is there are certain kids who can’t take a pill. But they can take beads.

They might be able to take a medicine like Adderall XR, for example, where they can open it up. Or Vyvanse, where they can open it up and spread it and take it that way. Some kids can’t even do that. Some need a solution or suspension, for which case they may have to use 1 of the suspension forms of the medication. I think that’s another important differentiation regarding the different extended-release compounds.

David W. Goodman, MD: It’s very interesting that you mentioned that, because in adults there are varying sensitivities. This idea that there’s weight-based dosing in adults is simply not a good way to follow this. I have patients who use low doses and have great responses. I also have patients who are on extremely high doses, and that’s what they need. I know in children you have guidelines for that, but I’ve heard you say that they are guidelines and really should not be the absolute dictation.

Timothy E. Wilens, MD: They are guidelines. A lot of people use up to 2 mg/kg per day of a methylphenidate in a kid, and up to 1 or 1.5 mg of amphetamine. But you’re right. For those people who are on higher doses that are way over FDA-approved doses or if you’re nervous about the dose, you can get levels. You can get levels of amphetamines, and you can get levels of methylphenidates.

Our guidance is to get them at peak. And again they’re optional. These are guidelines. Like Dave said, there is no 1-fits-all approach.

Transcript Edited for Clarity

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