Real-World Oxybate Use in Narcolepsy, Tolerability and Reduced Stimulant Dependence

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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 third episode, Meskill and Herpel reviewed REFRESH trial findings, emphasizing that real-world oxybate use in narcolepsy care demonstrated high tolerability, a low discontinuation rate, and meaningful clinical benefits. The duo highlighted that most patients with narcolepsy were already on other medications, including stimulants, and many could reduce or discontinue these therapies while on oxybates. They noted that the flexibility of titration in real-world settings, as opposed to rigid phase-3 trial protocols, likely contributes to lower dropout rates and better individualized patient outcomes.

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

Isabella Ciccone, MPH: Just to wrap up this conversation, do you either of have any closing remarks on this data and how it can help clinicians address some concerns for patients with narcolepsy, whether it be treatment adherence, tolerability, or long-term safety in general?

Laura B. Herpel, MD: I think that the tolerability can be challenging because there can be many adverse effects associated with taking oxybates, right? In the REFRESH trial, they did track the real-world adverse drug reactions or ADRs, that patients had. A lot of patients do have adverse effects, mostly nausea and GI-related symptoms. Typically, if you can work with your patient and educate them while they're taking their medications, then those tend to abate, or you slow down the titration. And I guess you work with your patient on an individual basis to address that.

But what was interesting in the REFRESH study is that they only had 3% of individuals actually discontinue because of intolerability of the medication. So that was impressive to me—to see that small of an amount—because even with adverse effects, patients seemed to tolerate the medication pretty well, and it’s very effective. So that was important to me.

The other factor that was important to me is that—71 or 72% of the individuals were already on other medications when they were placed on oxybates, which includes stimulants. Polypharmacy is huge in narcolepsy; patients are oftentimes on 2 or 3 different medications. How many patients were able to discontinue or decrease their stimulant dose throughout that study was impressive to me. And we know stimulants can have other comorbidities associated with them—the adverse effects of hypertension and tachycardia, and the long-term impacts on psychological issues with stimulants as well—we have to worry about.

So I think about those things when I'm committing my patient to a long-term medication. And because there were good outcomes—53% of patients that switched, and then somewhere around 50% of the non-switch patients were able to decrease their stimulant dose to some degree—that’s huge. That’s huge for me. So I liked that factor, and it does push me a bit more to consider oxybates as more of a first-line therapy for narcolepsy.

Gerard J. Meskill, MD: I think those are great points. One of the things that Herpel said that I’d like to expound upon was the low discontinuation rate in REFRESH. This is something that I talk to my patients about. When you look at the data from phase 3 clinical trials, whether it’s for once-nightly oxybate or one of the twice-nightly oxybates, it’s a pretty rigid schedule that is required to be followed. In the case of the once-nightly oxybate trial, everybody followed the same schedule up to the maximum dosage, so everybody was titrated to the maximum dose in the same timeframe.

In clinical practice, in the real world—which is why this is so great, looking at REFRESH—we don’t have to follow that rigidity. When you get experienced clinicians who participated in this, we did not titrate at uniform speeds. We did it based upon patient tolerance and response. Some people were able to titrate much more slowly and go up to a lower maximum dose. I think that speaks to why there was such a lower dropout rate compared with phase 3 trials, where there wasn’t that flexibility.

Laura B. Herpel, MD: Yes, I love that point. That’s a huge point for any clinical trial, I think. But it was nice to see that approach presented with some of this data.

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