Adult ADHD Treatment: Pharmacological Intervention


Anthony Rostain, MD, MA, provides an overview of stimulants, nonstimulants, amphetamines, and methylphenidates for adult attention-deficit/hyperactivity disorder (ADHD) treatment.

Theresa Cerulli, MD: Moving to a more complicated topic, how is ADHD being treated through pharmacologic interventions? We have so many choices now, it can be overwhelming. Can you give us an overview of stimulants and nonstimulants for ADHD, please?

Anthony Rostain, MD, MA: Sure. Just to summarize for the longest time we've known in studies with children that stimulant medications are highly effective in various domains. And over the last several decades, we now have comparable data in adults to say that stimulants are the first line of treatment because they reduce the symptoms of ADHD and improve functioning in various domains. Obviously, along with stimulants come some problems such as stigma or the possibility of misuse.

And the fact that they don't last around the clock. So as long as they're active in you, the stimulant helps you to do better in a variety of ways. But then when they wear off, you’re back to your baseline ADHD individual self. Nonstimulants have the advantage then of being around the clock. They work 24 hours, and they don't have the abuse potential that most stimulants do. And there's less stigma. On the other hand, there's less data overall. And the other thing about nonstimulant is you do have to take them every day. So, there's less of a take one day, skip another, which sometimes happens when people want to alter their treatment with stimulant medication. So sometimes we use both in combination depending on the complexity of the presenting problems.

And again, we can talk later if you want about the side effects from these different types of treatment. But we tend to prefer using the longer-acting preparations of the stimulants because adults tend to have longer days, and it's much harder to remember throughout the day and to keep a steady effect of the medication if you're using immediate-release stimulants. So, the big change in our way of looking at stimulants over the past decade or so has really been to look at the data and say, we get better adherence and fewer problems when we prescribe long-acting medication preparations.

Theresa Cerulli, MD: So, 2 questions come to mind. The first is, within stimulants there are amphetamines and there are methylphenidates, which can be confusing. How do you decide where to start? Do you have a preference for one category or the other? And if so, why? That's the one question. And it's because patients will ask, all the time, in practice. So, I'm curious how you approach that.

And then secondly, you mentioned some of the different formulations, immediate release, and extended release. Is there any data that helps us think about aids in treatment selection with regard to formulations?

Anthony Rostain, MD, MA: So, let's just start with the basic concept, which is overall methylphenidate has a very simple mechanism of action. It's really a reversible dopamine reuptake inhibitor that doesn't really do much more than block the transporter that's reuptaking the transmitter after it's been released. Amphetamine has a much more complex mechanism of action because it also makes more transmitters available in the vesicle. It also helps from the vesicle into the synapse. It increases the release of neurotransmitters. And we're talking about dopamine and epinephrine here. And it also reduces the breakdown, or the metabolism of the transmitter prismatically.

So, amphetamines are more complex in enacting; when you look at studies overall you could say there's a slightly higher effect size for amphetamines. And when you look at pharmacoepidemiologic data, it looks like about two-thirds of kids are on methylphenidate and only a third are on amphetamine. Around adolescence it's equal. And then in adults, the fractions are reversed. So, roughly, amphetamines are two-thirds to one-third depending on which study you're looking at.

Does that mean you should start with one or the other? I always say to talk with your patient about the difference in the profile. Find out if they've been on the medication before, many of our adult patients were treated as kids and have some remembrances of what did or didn't work and if other family members have been more or less successful on methylphenidate versus amphetamine. I don't like to say, “Well start with X,” because I do think that it really varies from patient to patient. If you're really concerned that a patient is not going to want to do more than one trial, then you're probably better off trying an amphetamine because there's a slightly higher effect size with amphetamines compared to methylate. But once again, you have a greater chance of side effects.

Theresa Cerulli, MD: Exactly.

Anthony Rostain, MD, MA: So, the appetite, suppression, insomnia a feeling of restlessness, a jitteriness, you are more likely to see. Now, with respect to what I think of as the immediate release are just what they sound like. They're released right away, and they're in and out within usually 4 hours.

When we use medications like mixed amphetamine salts extended release, what we have here is a biphasic release where half of the amphetamine is released immediately and the other half, is released about 4 hours later. People get confused with the term XR, extended release, because they think it means it's continuous, but it's really not. With mixed amphetamine salts XR, what you're really doing is giving an immediate and then a delayed release in 2 phases.

And then there are the more continuous-release preparations where you see over time the releases are distributed over, say, 8 to 10 hours and lasting up to 12 to 14 hours. And it's important to think about what the profile of the patient's problems are, and what's their day like. And that's why, for example, the continuous release is probably the one that I find is most widely preferred. But different strokes for different folks.

Transcript edited for clarity

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