Transcript: David W. Goodman, MD: While all of this is self-evident, it puzzles me and everyone in this field that 55% of all stimulant medications are short-acting, and 65% of all prescriptions for stimulants written in the United States are written by primary care physicians. How is it that this message simply doesn't seem to take hold in the prescription practices of many of the physicians seeing individuals with ADHD [attention-deficit/hyperactivity disorder]?
Theresa Cerulli, MD: Is there an evidence-based recommendation for hierarchy in choosing medications to treat ADHD? What can we recommend to our viewers?
David W. Goodman, MD: I suppose we'd have to rely on European guidelines. We don't have guidelines in the United States. I'm part of a working team that's developing these, but we're several years off in accumulating all of the research. The European guidelines, the Canadian guidelines, there are international guidelines that we can recite.
But again, despite reciting these guidelines and lecturing tens of thousands if not hundreds of thousands of prescribers, we still see the perpetuation of immediate-release stimulants. I know it may not be the wish of the clinician to prescribe this way. The incentives both economically and from insurance prior authorizations become major obstacles, and in my opinion, contribute to the ongoing perpetuation of the short-acting stimulant prescriptions being written.
Theresa Cerulli, MD: Ann, did you want to weigh in on the question of the evidence-based recommendation hierarchy for choosing medications?
Ann C. Childress, MD: Sure. If you want to look at adults, the recommendations are to start with an amphetamine. Amphetamines work better than anything else. They work a bit better than methylphenidate. There was a big meta-analysis that looked at more than 50 studies, more than 8000 adults, and what they saw was the effectiveness of amphetamines compared to placebo was highest. Methylphenidate was next, while atomoxetine was lower on the totem pole.
And when they looked at head-to-head comparisons, amphetamines were more effective than modafinil. Then, atomoxetine and methylphenidate. And regarding tolerability, interestingly, modafinil, amphetamine, methylphenidate, and atomoxetine were less well tolerated than placebo. That makes sense, right? Placebo shouldn’t have a lot of adverse effects, although I have had patients who have experienced horrendous adverse events with placebo.
And later, when we unblinded our studies, we found they were on placebo. There were only a few studies that compared dextroamphetamine with other amphetamines, but it's a little better tolerated than other amphetamines. So looking at all outcomes, amphetamines are the first-line choice for adults with ADHD. And I think that prescribing data bear that out in the United States.
Timothy E. Wilens, MD: I appreciate that. But also, as a clinician, I think the differences are nuanced. I think there is enough information on that, and it's really a choice of which one you want to use. Kind of what you were saying about the adverse effects, there may be an advantage in efficacy with amphetamine, or an advantage with methylphenidate for adverse effects and tolerability. And when you look at it in the end, it's pretty similar.
Theresa Cerulli, MD: Yes. Tim, you and I started to discuss the safe use of the stimulant medications. Did you have any comments, in terms of adverse effects and helping patients and clinicians? What is it you're watching for?
Timothy E. Wilens, MD: Theresa, you were mentioning that when you were talking about the contract, part of their contract is, “You're going to be monitored.” And that's actually important. In general, the stimulants have similar class effects. They can reduce your appetite, and they typically do that during the day. In the shorter term, you often will see weight reductions. And even longer term, you'll see continued weight reductions in those people chronically treated with stimulants.
Probably the more controversy comes around height. Is there really a height difference? I think most people would agree if you look at the literature that out 2 to 3 years there may actually be a mild reduction in height velocity. You don't shrink. Rather, you don't grow as fast. But if you look at that beyond 4, or 5, or 6 years, you lose that, there is some type of attenuation with that.
Having said that, you really do want to maintain height and weight examination of kids every 6 months to a year to see how they're doing. You want to keep an eye on those kids who really just stop growing.
In addition to that, Theresa, as you mentioned, you check blood pressure. There could be an increase in heart rate and blood pressure in individuals. Having said that, if you look at studies that were conducted by the FDA and AHRQ [the Agency for Healthcare Research and Quality] that were published in 2011, actually now almost a decade ago, in the best journals, they didn't really show any cardiovascular adverse events associated with stimulant medications over the long term. I think that is really important to know. They didn't show any in kids, and they didn't show any in adults. And in fact, if you saw anything, you saw a slight protective effect. Again, I'm not sure I buy that, but it was positive in terms of not showing real problems.
And finally, mental status issues. There are going to be kids who get more irritable on stimulants. Again, there are slight differences. Maybe a little bit more mood lability is found with the use of amphetamines over methylphenidates. But in the end, I think you're watching for that with all of them.
You can also see sleep issues. Again, as we said earlier, you can see these pre-existing. So it may be that they had a sleep disorder and you're only asking about it when they're being treated. And there, it pops up, but it actually was pre-existing.
The same with mood. It may be that they have a mood disorder and that got unleashed. Or, it actually was there before and you only saw it because you were now asking more systematically when people are on the medications. Those seemed to be the most important. There have really been no long-term effects seen. What you see short term is what you're seeing long term. You're not seeing ominous outcomes long term with these medications.
Transcript Edited for Clarity