Key opinion leaders in sleep medicine discuss the pitolisant studies and their experience using the drug in clinical practice.
Russell Rosenberg, PhD, DABSM: There were 2 pivotal trials with pitolisant that I’m aware of. These were conducted in Europe. The studies primarily focused on the use of the Epworth Sleepiness Scale, as well as a diary for cataplexy. They examined patients who had both NT1 as well as NT2 and who demonstrated significant improvements in both of these realms and had a fairly clean safety profile. Patients tolerated the medications quite well. As long as we’re speaking about Epworth, do you use that in your clinical practice? If so, how?
Margaret Park, MD: Honestly, I use it because I have to. It seems to be an insurance requirement to order tests. Epworth is a good scale. It gives you a common situation. You rank them on a scale of 0 to 3, according to your predisposition for sleep. I like it because I usually preface it by saying that it doesn’t mean you fall asleep. It’s to see if you can fall asleep with these situations. That’s 1 of the more clinically relevant scales that we have, in terms of paper-and-pencil things. The trap is always to make sure you don’t stick to that number. It’s meant to be used as a guide.
I’m in downtown Chicago, where not everyone has a car. One of the questions is, how often do you feel as if you can fall asleep in front of a stop sign or while you’re driving? Some people put 0 because they don’t drive. A lot of times I say, “Let’s pretend you’re driving,” because maybe they haven’t driven in 5 years. What do you do when you’re giving this scale to a 16-year-old? What do you do in someone who doesn’t read at night or doesn’t read in general? There are specific situations where people score 0 because they think it’s not applicable to them. Sometimes, the scores are falsely low. But if you preface it, go over the questions, and do imaginary situations, it can be a good clinical guide.
There has to be a cutoff because it’s a scale. There’s a relative cutoff of 10, meaning that over 10 is sleepy and under 10 is not sleepy. But I always caution people that it’s not a linear scale. When there’s improvement or deterioration 1 way or another, there’s a difference between going from a 24 to a 22 and an 11 to a 9. With anything else, make sure you put it into context with what the patient is doing.
Back in the day, in neurology residency, they were like, “He can’t be having seizures because his antiepileptic level in his blood is normal.” I’m like, “But he’s having a seizure right now. It doesn’t matter what the blood test says.” It’s the same thing with these scales is, make sure that you go over them. Make sure that it’s reflective of what you’re feeling with the patient. I find that using them as a clinical marker over time isn’t as useful because these medications don’t completely eliminate sleepiness. What they do is control sleepiness. You can take the medicine and take a nap. The idea is that if you want to stay awake, it shouldn’t be as much of a fight.
Part of the problem with the scale is that it’s putting it into the context whether you can fall asleep in this situation. Yes, of course I can. Just because they haven’t had movement in the scale doesn’t mean that they’re not treated well. Movement on the scale doesn’t also mean that they’re well controlled. Putting it into context is a good idea. But as a researcher, you have to include these scales because we need some sort of subjective measure. Because most sleep studies use these scales, it’s useful to compare apples to apples.
In the HARMONY studies, they compared the low, medium, and high doses. The therapeutic doses are the medium and high doses. They compared the medium dose of 17.8 mg with the maximum dose of 35.6 mg. Most of these patients had narcolepsy type 1. Most had a very high upward scale. One of the primary end points was movement on the Epworth scale. They wouldn’t have reported it if wasn’t good. It definitely showed statistical significance. That matches clinically. The medication works in modulating sleepiness or lessening that fight of sleepiness in patients who take it.
Russell Rosenberg, PhD, DABSM: What’s your thought about the fact that pitolisant—you’ve mentioned this before—isn’t a controlled substance? Does that make you think about using it in a different way from, say, the scheduled drugs?
Margaret Park, MD: I do. Going back to case 2, it’s not uncommon for people to come in and say they’ve had a history of substance dependence. Maybe not abuse necessarily, but they heavily relied on 1 thing or another at 1 point in time. To me, why poke a sleeping bear, especially if they’re not doing it anymore? Frankly, people say, “I’m a former whatever-substance user.” I like this medication because it gives them something without bringing up these concerns. I also have patients who may not have a substance history, but everyone in their family has a substance history, so, they’re very cautious about entering into that arena. This medication makes them feel a little more comfortable.
Aside from substance-use and substance-abuse history, we also see people who have other medical issues—uncontrolled high blood pressure, eating disorders—where 1 of these other medications may suppress appetite. But when it wears off, the appetite comes back and they start bingeing. In people who have other disorders outside that sleep or substance realm, it’s a nice way of being able to manage something without constantly turning someone on and off. It’s a relief to have something outside the traditional thoughts of how we manipulate sleep and wake.
Russell Rosenberg, PhD, DABSM: Do you find it more difficult to prescribe pitolisant to someone who has been on Adderall or another stimulant already? If they’re going to discontinue those, do you make the switch reasonably easy?
Margaret Park, MD: They do If you set it up the expectation. A lot of times I will continue their medicines for that first 2- to 6-week period, until the pitolisant after can be apparent, because there’s a slow-dose titrating schedule and the effect isn’t apparent immediately. That’s what we tell people: “Continue your medicines for now. Let’s keep updating each other weekly for dose titration. Once you start feeling an effect, then maybe we’ll slowly come down on these other medications.” Sometimes it’s a happy medium. Sometimes we’re able to come all the way off.
If they know it takes some time and that we’re not going to completely stop these medications, then there’s a big fear of losing something when you gained it. For years, if these people were sleepy or had these issues but were then, all of a sudden, able to focus—they’re alert and able to get to their jobs—then maybe you say, “You know what? I’m going to take it away suddenly.” It feels threatening, and it’s difficult. We slow up and slow down to make sure people feel as if they’re in control and that they can understand how these things work and what to expect. A slower process with pitolisant is a very necessary conversation you have to have with patients.
Transcript Edited for Clarity