With more therapies available, it’s time to revisit the concerns of people with narcolepsy.

By Sree Roy

Sleep physician Lewis J. Kass, MD, wanted to help his narcolepsy patients who started sleep-eating between the first and second doses of sodium oxybate, a known side effect. 

He adjusted the dosing, increasing the first and lowering the second, which helped. More recently, he switched these patients to a once-nightly version of sodium oxybate to try a simpler solution. Of the eight patients who started LUMRYZ (the once-nightly sodium oxybate the Food and Drug Administration approved in 2023), all stopped sleep-eating within six months; five also lost weight.

Why Ask Now

This small sleep-related eating disorder SLEEP 2025 abstract may not directly translate to the broader narcolepsy population. But it highlights a larger point: with multiple FDA-approved and cleared drugs now available for narcolepsy symptoms, it’s a better time than ever to ask patients about side effects, lingering symptoms, and issues that physicians may have overlooked before. You might finally have options to offer.

“It starts to open up the door for these conversations to take place,” says Jennifer Gudeman, PharmD, senior vice president of medical and clinical affairs at Avadel, marketers of LUMRYZ and funders of Kass’s sleep-related eating disorder study. “There’s been a reluctance of patients to voice the challenges they had with middle-of-the-night dosing, historically, because they didn’t have any other option. Now that there is an option, there’s a much more direct line of communication that’s happening, where patients are willing to talk about things like sleep-related eating disorder or missing doses, taking doses late, taking doses early, et cetera, et cetera.”

More Drug Options

It’s not only middle-of-the-night dosing-related challenges that could potentially be addressed in today’s narcolepsy pharmacotherapy landscape. The growing roster of narcolepsy drugs in the United States brings different indications, side effects, drug interactions, Drug Enforcement Administration scheduling, and approved age ranges.

There are three forms of oxybate (brand names XYREM, XYWAV, and LUMRYZ). There is pitolisant (brand name WAKIX), which is the one FDA-approved option for excessive daytime sleepiness and cataplexy in narcolepsy that’s not a controlled substance. There is a wake-promoting drug that works by increasing the levels of dopamine and norepinephrine in the brain (brand name SUNOSI), as well as several stimulants. On the horizon, there are the orexin agonists.

Specific Topics to Discuss with Narcolepsy Patients

This means sleep physicians can now explore concerns like:

• Continued excessive daytime sleepiness: An interim analysis of Avadel’s REFRESH study found that narcolepsy patients whose Epworth Sleepiness Scale remained high had their scores enter the normal range after switching to LUMRYZ. About half the patients in the real-world study who had previously been on twice-nightly oxybates admitted to sometimes missing doses, says Gudeman, one of the study’s investigators. This could be a good time to either have patients recommit to proper twice-nightly dosing or trial an alternative. 
• Hypnogogic/hypnopompic hallucinations: Even though hallucinations when falling asleep and waking up are a known symptom of narcolepsy, some patients are reluctant to mention these to doctors for fear these events could be misinterpreted as “a sign of psychosis or other psychiatric disorder,” according to Gudeman. The good news is a post-hoc analysis from the phase 3 REST-ON trial of LUMRYZ reports that only half the number of hallucinations where participants felt like they were about to be attacked, flying through the air, and falling in a hole were reported with once-nightly sodium oxybate versus placebo. Also, the study showed a strong placebo effect—so perhaps simply having an open dialog with narcolepsy patients about hypnogogic/hypnopompic hallucinations could stem these events.
• And of course, sleep-eating. Kass’s eight narcolepsy patients likely feel empowered after having this problem recede from their lives. 

By asking patients about their narcolepsy drug side effects, sleep physicians open the door to better medication adherence and outcomes.

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