Deciding Which Drug to Use in Narcolepsy

Michael J. Thorpy, MD: There are a number of different medications now available to us for the treatment of narcolepsy. How do we decide how we’re going to treat a patient with narcolepsy? Do you have a particular sort of algorithm you use, Alon, for treating narcolepsy? What would be your first sort of go-to drug for narcolepsy now?

Alon Y. Avidan, MD, MPH: That’s a really important question. I do not have an algorithm that I put the patient through and then that’s the only algorithm I follow, because all of these medications have their pluses and minuses. Patients may present with narcolepsy as a different phenotype, in that some patients may have underlying depression or anxiety. Some may have certain underlying comorbidities for which some of these agents may not be the most appropriate first-line therapy.

As a general rule, for folks who have narcolepsy type 1 and type 2, the most commonly prescribed group of drugs is the wake-promoting agents. And the advantage here: It’s a once-a-day, perhaps twice-a-day formulation. Patients take it in the morning. They may follow with a second dose later in the morning or early afternoon. We may be able to, at that point, assess the patient and evaluate whether to prescribe additional therapy. And for those individuals, if they do feel sleepy at 1 o’clock, 2 o’clock, or if they feel so sleepy that it’s affecting their driving, then a short-acting methylphenidate medication would actually be effective.

Now, the other patient who presents with excessive daytime sleepiness and cataplexy, where the cataplexy is quite frequent, would probably be most appropriately treated with sodium oxybate—and have 1 drug that addresses multiple facets of the disease by being taken at night, with a second dose 2 to 4 hours later. The advantages here are both improvement of daytime sleepiness and very effective improvement of cataplexy. Bear in mind that a lot of patients who have cataplexy may have a few episodes per week or may not require traditional therapy or a specific therapy for cataplexy itself and are able to manage it by avoiding situations—nothing that I would advocate the patients do, but they may not require a specific therapy directed at the cataplexy.

I think that with the new agents—pitolisant, solriamfetol—having the ability now to provide treatments for those who still have daytime sleepiness with the traditional stimulants and the wake-promoting agents—and knowing that 10% to 60% of those patients still experience significant daytime sleepiness that is paralyzing them—providing add-on therapy is probably going to be advocated for. Then we would have to experiment with multiple add-on therapies based on the patient phenotype.