Simplifying Narcolepsy Treatment: Insights on Once- vs. Twice-Nightly Oxybate

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Once-nightly oxybate (Lumyrz; Avadel Pharmaceuticals), initially approved in 2023 for adults with narcolepsy to treat excessive daytime sleepiness and cataplexy, had its indication expanded in late 2024 to include patients aged 7 years and older.^1,2 Researchers presented new findings from the multicenter observational REFRESH study, assessing the efficacy, satisfaction, and safety of once-nightly sodium oxybate, at the 2025 World Sleep Congress, held September 5-10, in Singapore.³

The goal of REFRESH is to understand more about the real-world experiences with once-nightly sodium oxybate, as well as gain insights for decision-making between twice-nightly and once-nightly solutions. Recently, NeurologyLive^® held a roundtable discussion with 2 sleep experts who talked about the real-world data from the REFRESH study presented at the Congress. Panelists in this conversation included Gerard J. Meskill, MD, the founder and CEO of Tricoastal Narcolepsy and Sleep Disorders Center in Sugar Land, Texas, and Laura B. Herpel, MD, a sleep physician at Bogan Sleep Consultants in Columbia, South Carolina.

In this fourth and final episode, Meskill and Herpel highlighted the clinical impact of simplifying oxybate dosing for patients with narcolepsy. The duo of experts discussed how once-nightly dosing may improve adherence and reduce the burden of waking in the middle of the night, while noting that twice-nightly dosing remains effective for some other patients. Both experts emphasized the need to tailor therapy to individual patient lifestyles and comorbidities, such as sleep apnea or asthma, and the importance of considering treatment switches when patients are not achieving optimal outcomes.

Transcript edited for clarity. Click here to view more of our coverage on sleep disorders.

Isabella Ciccone, MPH: Any other last closing remarks before we close off the conversation?

Gerard J. Meskill, MD: I think that the key thing looking at REFRESH, looking at once-nightly oxybate, we know in clinical medicine, no matter what the agent is, the less complicated the dosing schedule is, the higher the adherence or compliance. Inherently, as effective as it is and as a narcolepsy physician, I use twice-nightly oxybates readily, in addition to once-nightly. But there is an inherent challenge, at least for some people, that you're asking a person of profound sleepiness to wake up in the middle of the night and take a medication and be cognizant enough to know what time it is, how long it has been from the first dose, to not make the mistake of accidentally taking it too soon. Also to be able to wake up in the first place.

There is inherently an easier schedule to follow when you just have to take a medication at bedtime and not a second time in the middle. And I think a lot of the data that we saw with REFRESH underscores that, in terms of people switched over—that they were having improvement in their upward sleepiness scale above and beyond already being on oxybate, that they were having improvement in quality-of-life metrics, in occupational metrics, that 92% said the second dose was burdensome, and that four-fifths were missing doses at least some of the time. These are important data points.

Laura B. Herpel, MD: I think one of the last things that we probably should touch on is, we do use all these medications for our patients. We need them all in our armamentarium to treat this disorder, because every patient is unique, and every patient is different. They need a medicine tailored to what they can do, their lifestyle, and what's going to be the most effective for them.

One of the things that I want to see moving forward is looking at some other comorbidities and the impact of the medication on other comorbidities—patients who have sleep apnea, because it's more common in narcolepsy. Are we safe in using it with sleep apnea? See the patients that have asthma and trial the medication in them? And is there a difference between type one and type two? We don't know those things yet by a lot of this data. But I think the fact that if you have a patient that's not doing up to par, as well as you had hoped on an alternate medication, certainly switching seems to potentially benefit. And if it doesn't work, then you go back. I mean, I think it's definitely worth the trial to see if you can get added benefit for people who are not doing as well as you would hope.

Gerard J. Meskill, MD: Yes, I agree with Herpel on that, too. The bottom line is, even in 2025, where we've got more options for narcolepsy than we ever did before. It's still not that many options. So I would encourage my colleagues—fellow neurologists and sleep specialists who are watching us—not to, out of rote, write off a potential treatment option, a standard of care. The bottom line is, with narcolepsy, one, we don't have a lot of choices. And two, we've got a lot of data on this now, whether it's twice-nightly or once-nightly, that oxybates move the needle for narcolepsy as much or more than anything else that we have.

Isabella Ciccone, MPH: Perfect. Thank you all for answering my questions for this roundtable, but that will conclude this conversation. I appreciate both of you and the insights that you could bring to our audience of neurologists, in case any of them may have missed the World Sleep Congress. This is just a great way to keep them informed. So, thank you very much.

REFERENCES
1. Avadel Pharmaceuticals announces final FDA approval of Lumryz (sodium oxybate) for extended-release oral suspension as the first and only once-at-bedtime oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy. News release. Avadel Pharmaceuticals. May 1, 2023. Accessed November 5, 2025. https://www.globenewswire.com/news-release/2023/05/01/2658536/0/en/Avadel-Pharmaceuticals-Announces-Final-FDA-Approval-of-LUMRYZ-sodium-oxybate-
2. Avadel Pharmaceuticals Announces FDA Approval of LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension (CIII) for the Treatment of Cataplexy or Excessive Daytime Sleepiness in Patients 7 Years of Age and Older with Narcolepsy. News Release. Avadel Pharmaceuticals. Published October 17, 2024. Accessed November 5, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-fda-approval-lumryztm-sodium
3. Avadel Pharmaceuticals to Present New Data on LUMRYZ™ (sodium oxybate) for Extended-Release Oral Suspension at World Sleep 2025. News release. Avadel Pharmaceuticals. September 5, 2025. Accessed November 5, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-present-new-data-lumryztm-sodium-0