Traditional Treatments for Narcolepsy

Michael J. Thorpy, MD: You really need to have comprehensive management of a patient diagnosed with narcolepsy, and it’s important to deal with the lifestyle, psychosocial aspects as well. With regard to the medications, Alon, what medications do we currently use for narcolepsy?

Alon Y. Avidan, MD, MPH: The traditional medications for narcolepsy have been psychostimulants, which have probably been around the longest. They do work. They work very effectively, but they often have some adverse effects often related to their mechanism of action of being somewhat sympathomimetics.

Michael J. Thorpy, MD: Specifically, you’re talking about the amphetamine agents and methylphenidate, is that right?

Alon Y. Avidan, MD, MPH: Exactly. In the 1990s, we saw the development of 2 medications that share 2 different mechanisms of action. One was a wake-promoting agent. We’re specifically talking about modafinil. And later on, armodafinil, the (R)-isomer of modafinil. The wake-promoting agents have the advantage of being taken once a day without inducing the sympathetic hyperactivity, which is often unique to the amphetamine-type medications.

Sodium oxybate also came around at the same time. Sodium oxybate is very different than the traditional stimulants because it’s not a stimulant and it’s not taken during the day. We give it at night, and it works by fundamentally improving nocturnal sleep. When nocturnal sleep is improved, daytime functioning improves as well. So it is, in fact, a hypnotic, and it does work in consolidating nocturnal sleep. So those were the 4 primary treatments up until recently. With newer ones now available, we have new mechanisms of action and new opportunities for management.

Michael J. Thorpy, MD: Do the traditional stimulants and the modafinils have any effect on cataplexy, or are they just for the sleepiness?

Alon Y. Avidan, MD, MPH: The traditional stimulants do have some effect on cataplexy. The traditional wake-promoting agents do not. That is 1 differentiation, although the wake-promoting agents are not marketed or prescribed specifically to address cataplexy. But if we have someone with narcolepsy type 1 who has more difficulties with cataplexy, certainly a stimulant may have better activity. However, the 1 drug—currently the only drug—in the United States that actually has an impact on cataplexy is, in fact, sodium oxybate.

Michael J. Thorpy, MD: That’s the only one that’s FDA approved. When those stimulants do have a slight effect on cataplexy, do you think it’s mainly because they are affecting the alertness and sleepiness and, therefore, there’s not that pressure for developing cataplexy? Or do you think it’s a more specific effect on cataplexy?

Alon Y. Avidan, MD, MPH: I think it’s more of the former. They do tend to affect alertness and indirectly reduce the propensity for going into REM [rapid eye movement] sleep or inducing a REM intrusion, rather than specifically working on the underlying mechanism of action of cataplexy.

Michael J. Thorpy, MD: Now Kiran, are these same medications used for children?

Kiran Maski, MD, MPH: Yes. For children, I think psychostimulants are probably the most commonly used. The only FDA-approved medications are psychostimulants. And, as of 2 years ago, sodium oxybate. There was a clinical trial showing efficacy, so that’s been added to our regimen.

Michael J. Thorpy, MD: So the modafinils are not approved for children?

Kiran Maski, MD, MPH: Well, modafinil is not approved for children younger than 17 years, but certainly is used clinically and has been shown to be fairly safe. The reason it wasn’t approved for daytime sleepiness is because there were a handful of cases of Stevens-Johnson syndrome. And patients should know that if taken, it can interfere with birth control, so there’s maybe an increased risk of pregnancy. So those are some considerations. Otherwise, for children we use SSRI [selective serotonin reuptake inhibitor] and SNRI [serotonin-norepinephrine reuptake inhibitor] medications to treat cataplexy.

Michael J. Thorpy, MD: You mentioned that sodium oxybate was only just recently approved for children?

Kiran Maski, MD, MPH: Yeah. It was recently approved for the treatment of daytime sleepiness and cataplexy in children aged 7 and older. In those trials, it was shown to be very effective for the treatment of cataplexy and sleepiness. Adverse effects ranged from a whole host of minor things—including nocturnal enuresis, dizziness, feeling unsteady on the feet, and weight loss—to a few cases of more severe adverse effects, such as affected mood and the development of central sleep apnea. There was even a case of suicidality in that cohort.

Michael J. Thorpy, MD: But in general, is it fairly well tolerated in children?

Kiran Maski, MD, MPH: Yes.

Michael J. Thorpy, MD: People have been concerned about sodium oxybate because it’s a derivative of gamma-hydroxybutyrate, and there have been a lot of questions about using that in adults. And yet, this drug is FDA approved for children. So in general, do they tolerate it pretty well?

Kiran Maski, MD, MPH: Yes. So the patients benefit because it treats multiple symptoms of narcolepsy. It treats the daytime sleepiness. It treats the nighttime sleep disruptions. It treats cataplexy. So, in many ways, using fewer medications for the pediatric population is an advantage. And they do tolerate it well. The dosing is different than it is for the adult population. Oftentimes, I’ll slow the titration in the pediatric population. That helps avoid some of the adverse effects that I talked about. But you do have to counsel them and follow them closely for any mood-issue concerns that may develop along the way.