Transcript: Theresa Cerulli, MD: David, when do you switch between drugs of the same class, such as switch from a methylphenidate to another methylphenidate, versus switch from one class to another class of medications, such as switch from a methylphenidate to an amphetamine?
David W. Goodman, MD: This is a very important question for clinicians. When patients don't respond or start having adverse effects, and they say, “Look, I don't really want to continue taking this medicine,” what is the clinician to do? If you have 28 different stimulant preparations, how do you decide, besides throwing a dart at a dartboard? Well, let me give you some parameters for that. For me, if the patient gets better on the compound—let's say they're on a methylphenidate and their symptoms get better, their daily improvement is better—then I'll stay with the same compound.
But if they say they have adverse effects on that compound, then I'm going to look at the technology, the delivery of mechanism into the system. And to sort that out, I'm going to then assess whether those adverse effects occur an hour or 2 after they take the medicine, or 6 hours, where there is a plateau, or whether it's occurring 8 to 10 hours later, when it's wearing off. Depending on when the adverse effect is occurring in the time frame of the duration, then I will alter the technology that I choose—the delivery system.
Let's say the patient is on a beaded preparation, like amphetamine mixed salts XR [extended-release], and their drop off effect is too fast. They get irritable. They get lethargic. They get moody. So now I want to extend the duration. I'm probably going to change to a different duration of action. I'm going to change to a triple beaded option, or I may use lisdexamfetamine as a prodrug that has a different delivery system. To back up, if the patient gets better on a compound but they have adverse effects, then take a look at the timing of the [adverse] effects. See if you can then change your technology within the same compound. If the patient doesn't respond to a compound, then I'll change to a different compound.
I don't go from methylphenidate to dexmethylphenidate. Rather, I'll go from a methylphenidate to a dexamphetamine, or vice versa. I think this is an effective way of sorting it out for clinicians, thinking through the algorithm of choosing, preferably, a long-acting stimulant medication.
Often, what clinicians will do is they'll start with a long-acting medication, titrate it up, and the patient will say, “It's wearing off at 3 o’clock or 4 o'clock.” Then they give the patient an immediate-release booster to get them another 4 or 5 hours. I've been an advocate of not doing that. If you increase the milligrams of the long-acting in the morning, you will extend the duration out. For example, clinically, if using lisdexamfetamine, if I go up 10 mg, I'll get another 2 hours of duration. If I go up 10 mg on mixed amphetamine salt XR, I'll get another 2 hours duration. So if you know that, I would increase the morning dose of the long-acting to increase the duration. Unfortunately, sometimes when you do that the adverse effects will occur on part of the PK [pharmacokinetic] profile. And that's the dose at which the patient can't tolerate the drug. That's the way to think through, do I go from compound to compound, or do I stay within the compound category and change the delivery system for duration of action?
Theresa Cerulli, MD: Thanks for sharing your thought process on that, David. Anyone else have a different approach they might use?
Timothy E. Wilens, MD: Regarding the addition or supplement of using immediate-release with extended-release, I'm probably a little bit more liberal than Dave, I also use it in individuals during the afternoon when they sometimes have to work longer. Sometimes they don't, but that allows them the option to do that.
The other thing I wanted to comment on, to what Dave was saying, is that when you're going within or between different preparations, I think it's important also to remember, are you talking about a racemic mixture or are you talking about am isomeric mixture? If you're moving from dl-methylphenidate to d-methylphenidate, you're going to do that often because you have some efficacy, need a little bit more efficacy, and want to get better adverse effects.
And the same goes with amphetamine. Regarding amphetamine, I think people forget that many of the compounds, such as if you're using the mixed amphetamine salts—Adderall, Adderall XR—that's going to be a D, L preparation. It's not going to be the racemic. It's going to be mixed.
If you go to d-amphetamine, as you were hearing—let's say with Vyvanse or some of the other ones, like Evekeo that have more of a D to L—you're really moving more to the isomeric preparation. That will buy you a bit more efficacy with fewer adverse effects. I think that also becomes sort of nuanced.
Transcript Edited for Clarity