Advances in the Management of ADHD in Adult Population - Episode 9

Different Formulations of ADHD Medications

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Dr Feld highlights several formulations that are available to treat ADHD.

Theresa R. Cerulli, MD: Let’s segue into a question for Dr Feld. What about different formulations in terms of duration of action of ADHD [attention-deficit/hyperactivity disorder] medications?

Michael Feld, MD: I’ll take that to a different level because this is my fascination. I totally believe in the biotechnology. All of us have been on adviser panels for all the companies that have come up with the new formulations. In the last 20 years, the evolution of the delivery of these molecules has made it so that many more patients are more willing to take the meds. They get better length of action, better onset, and less use of immediate-release [IR] stimulants. We’re trying to use them less because of tolerability and abuse potential.

I’ll go across the board. We previously had 1 D-methylphenidate extended-release product. It had a beta IR-delivery system. We have a new D-methylphenidate product, an IR medicine added to a prodrug delivery similar to LDX [lisdexamfetamine dimesylate], or Vyvanse. It’s the SDX [serdexmethylphenidate] of this new medication. The goal of all these new meds is to have quick onset in a delivery system that you have the consistent response day in and day out. A lot of the older delivery systems have failure or some issue where you don’t always absorb it, so you don’t always feel the same way as far as the efficacy and tolerability and length of action. The goals are onset, tolerability, and length of action. As Andy pointed out, the easier drop-off you have, the less aware you are of coming off this med. Not only do you have greater sense of length of action, but you also feel better at the end of the day.

More than anything else, the new delivery systems carry the same risk of adverse events, but everybody experiences them differently. There could be 3 kinds of appetite suppression and 3 kinds of amphetamines. You could be disgusted by the smell of food. You could take 2 bites and be full. You could think, “I’m not really hungry. But if you give me a slice of pizza, I’ll eat the whole thing.”

The 1 adverse event that nobody talks about is that it stops most kids and adolescents from taking meds if they’re feeling blunted, quiet, like they’ve lost their personality. These new delivery systems are all about the continuous release of a molecule. Instead of getting it with a bolus release, you have a more gentle feel. It’s much less blunt, and there’s less of a crash at the end of the day. We prepare patients to be open to these new meds.

What do we have? We have the new D-methylphenidate delivery system, which I described. There are 3 more recent D- and L-methylphenidate products. One is Ritalin. One is a medicine that you take at night, called the Delexis delivery. But because of what happens, it doesn’t kick in for 10 hours. You can time it to wake up with your medication working. With that medicine, if you kick the dose up high enough, you get length of action in the evening.

As Andy pointed out, there’s a preparation called a microparticle delivery, which is made by 1 company. It’s extended-release D- and L-methylphenidate liquid. The cool part about that is there are 24 doses. You can fine-tune the dose, or find the dose you feel the best at. You can flex your dose, so on a different day you take different amounts. You can reverse titrate easily if you overshoot it. There’s an ease from administering a month’s worth and not having to keep refilling early as you titrate. That same product has a chewable tablet that has the same biotechnology. It’s just a different formulation. Another company has a similar but different extended-release methylphenidate product that’s a D- and L-methylphenidate, a different type of microparticle, and it comes in an oral disintegrating tablet [ODT]. Because of that, there are different issues with portability and not having to swallow water. All these meds that we’ve talked about—the evening med, the D-methylphenidate, and the 2 D- and L-methylphenidate—don’t have to be swallowed. They can even be sprinkled. We’re getting away from the concerns about swallowing tablets or capsules.

In the final 1, I said there’s an oral disintegrating tablet that carries good onset, with the same or more consistency and good drop-off. Then you have 2 amphetamine products—2 companies that make different delivery systems of meds. In the amphetamine category, you have 1 simple product that’s fifty-fifty D- and L-methylphenidate. The more common amphetamine product is mixed amphetamine salts. We know that mixed amphetamine salts XR is more of a beta-delivery system of 2 IR doses. There are some limitations with that, even though it’s very common and a fairly well-tolerated med.

There are 2 meds made by 2 companies, the same companies that make the D- and L- methylphenidate liquid and D- and L-methylphenidate ODT. One has the mixed amphetamine liquid, same advantages of the methylphenidate liquid. That same company just developed a tablet, which I know we’ll be talking about. It’s a very cool formulation on a delivery system that’s the exact same chemical structure as mixed amphetamine. It’s the same company that has an extended-release mixed amphetamine oral disintegrating tablet.

You can see that this goes along with your LDX product, which is long-acting dextroamphetamine. You have the mixed amphetamine salt XR product, which we’ve talked about. You have a couple of more common methylphenidate products, like the OROS [osmotic-release oral system] delivery system. You see the evolution of these 6 new meds that I just talked about. They’re game changers in terms of avoiding IR augmentation and getting people to have a quick onset, consistent delivery with a good length of action, and finding a med that they’re more willing to take.

That was a long answer, but it’s truly my passion. It’s what treating ADHD is about right now.

Theresa Cerulli, MD: Thank you for that thorough list of changes we’ve seen in the field with regard to the biochemistry of the stimulant medications.

Transcript edited for clarity