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Improving Diagnosis and Patient Outcomes in Narcolepsy - Episode 13

Optimal Use of Narcolepsy Medications

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Drs Margaret Park and Russell Rosenberg share considerations for the use of solriamfetol, lower-sodium oxybate, and pitolisant in narcolepsy for various patient populations.

Russell Rosenberg, PhD, DABSM: With solriamfetol and lower-sodium oxybate, I think I know how you’re going to respond to this, but I want to ask you: is there an ideal medication for each patient? Do you always consider all the drugs? How do you do this? It’s probably pretty complex.

Margaret Park, MD: It’s always complex. Is there an ideal situation for anything? There’s not 1 perfect pill. There’s not 1 perfect situation. There never is. I always tell people that if you’re looking for this perfect solution, this perfect magic pill, I don’t have it. Let me know if you because I’d love to take part in it. We’re not going to be able to say that everything is a 100%. But we have to live in this medium of what is better. On the flip side, people say, “I feel better on this medication.” And I say, “Are you still awake during that meeting?” They say, “Yeah. I’m still jabbing my thigh with a pen, but at least that’s working now. It wasn’t working before.” And then we come back to, well, maybe they’re not alert enough, because thigh injury from a utensil isn’t the ideal situation.

We constantly remodulate. On the other hand, if people say, “How come my friends are staying up all night? They get 4 hours of sleep and drive.” Because they don’t have narcolepsy. If you think this medication regimen is going to turn you into that, I’m the wrong doctor for you. I can’t do that. If you find someone who can, let me know. I’ll start referring my patients to them. There’s no magic bullet. There’s no magic pill. It’s a lot of manipulation of what you should expect and what you shouldn’t.

When it comes to the oxybate family, I like this medication a lot. It was a game changer from my perspective because a lot of times we focus on the day and we forget that there’s sleep fragmentation. There’s sleep disruption. Maybe not subjectively, but we do see that on PSG [polysomnography]. We know that from research. The endgame of oxybate is to consolidate sleep, to give you a really deep sleep…so that when you do come up, you feel as if you’ve slept. Your sleep quality is better because. We forget that it’s not just wake and sleep that are disrupted against each other. It’s also within the sleep realm—the different players of sleep are fighting among themselves because there isn’t that orexigenic influence to manage them.

One thing the oxybate family does is it makes them a little more ordered and work a little differently, so that the sleep you get feels as if it has more quality. If you think of all these symptoms—sleepiness, unfocused attention, cataplexy, hallucinations, sleep paralysis—as being intrusions of sleep into wakefulness, the idea is that if you’ve slept, maybe they’ll intrude less.

Even though it’s considered a nighttime medicine, [oxybate] has heavy influence during the day. I find it to be a very good medication for people whose primary complaints are, “I can’t get out of bed. I’m constantly late to work. I need 7 alarms to get up. I need to do complex puzzles to get my system going.” It’s a nice complement to whatever we’re doing for the day. For people who have day issues, whatever medication I give them, whether it’s 1 of the traditional adrenergic medicines or even pitolisant or solriamfetol, if they’re not liking these medicines or if they’re having adverse effects, sometimes the night approach works very well. Oxybate is a very good medication. Do I think it should be the only medication? No, but I often don’t have a lot of people on monotherapy in any realm of medications.

Russell Rosenberg, PhD, DABSM: Pitolisant has been FDA approved for treating both EDS [excessive daytime sleepiness] as well as cataplexy. The same is true with lower-sodium oxybate, but solriamfetol is only for the EDS component. I imagine you consider those: the strengths and weaknesses of each medication. Do you use pitolisant with, say, sodium oxybate?

Margaret Park, MD: I do. It can be safe. Yes, a lot of pharmacokinetic [PK] profiles have come out looking at 1 FDA-approved medication vs another. Outside research reports look at non-FDA-approved medicines that we commonly use for narcolepsy anyway. We find that with the oxybate and daytime medications—at least with the modafinils—there isn’t a PK interaction between them. I don’t think there’s anything up to date with solriamfetol and oxybate. But presuming that it’s within the same line, I don’t think there’s a cross-reaction. In other words, you can take them both safely, as long as you’re being monitored by someone.

The biggest issue with oxybate isn’t so much what I’m giving people during the day. It’s more what they’re doing before bed. Alcohol, especially during the COVID-19 pandemic, has been a big concern. I caution people all the time: you can’t mix alcohol with this medication. People also forget that if you’re sick with this and you need an over-the-counter substance, those substances sometimes have alcohol in them and very frequently have antihistamines. Thus, if you’re taking something over the counter or taking something new, skip the medicine. The nice thing about oxybate is if there isn’t a maintenance thing. You can take it 1 night, skip it the next night, and come right back to it the following night….

I wish that if you had narcolepsy, you were immune to food poisoning, hypertension, cancer, or dementia, but that’s not true. You still have to go get your mammograms and colonoscopies, because it doesn’t make you immune to those things. If there’s a question, skip it. If you had a glass of alcohol and you’re wondering if there was enough time that went by before you can take the oxybate, then skip it. It’s no big deal because you’re not changing your disease management. You can return to it the following night when you haven’t had alcohol.

The other concern is sleep apnea. About 25% of people with hypersomnia disorders, probably more, can also develop sleep apnea, because sleep apnea doesn’t have to be about weight. It doesn’t have to be about snoring. There are metabolic consequences in sleep apnea, and a lot of those metabolic changes occur within that hypothalamic region. That’s right where orexin is affected and where narcolepsy hits you. I always screen people for sleep apnea because oxybate can be a respiratory depressant. We do take a look at that.

The other big other issue with oxybate is mood. I tell people, “You have to be very good about knowing what your mood feels like.” For lack of a better term, this is a heavy downer. I’m pushing you down to sleep. That means that if it’s overworking, then during the day you’re also going to feel pushed down. Depression is a common manifestation, even if you weren’t aware of it before. Subsequently, it’s a serious medicine. You have to have a serious talk with patients, but it can work very well to manage multiple symptoms across the board. Whether you think about it as day or night, it helps stabilize those 2 systems.

Transcript Edited for Clarity