In this special report series from NeurologyLive, leading sleep medicine experts Eric Olson, MD, and Anita Shelgikar, MD—president-elect of the American Academy of Sleep Medicine—offer their perspectives on six late-breaking presentations from the 2025 SLEEP Annual Meeting in Seattle, Washington. With a focus on narcolepsy and hypersomnia, the panel provides timely insights into new and emerging data that could influence future clinical care.
Throughout the series, the discussion covers a range of pressing topics, from cardiovascular safety and high-dose efficacy of low-sodium oxybate to investigational therapies like TAK-861 and ALKS 2680. The panel also unpacks trends in prescribing behavior and the influence of social determinants of health, offering a comprehensive look at the evolving treatment landscape for central disorders of hypersomnolence.
This second episode focuses on early data from the DUET cohort exploring low-sodium oxybate doses above the approved 9-gram ceiling in narcolepsy care. Drs. Olson and Shelgikar discuss reported symptom improvements, tolerability signals, and the potential for individualized dosing in complex cases. They also reflect on the importance of comorbidity management, especially sleep apnea, and consider the need for longer-term data to confirm these initial findings.
Transcript edited for clarity.
Eric Olson, MD: The second abstract to discuss is titled “Effectiveness and Safety of Low-Sodium Oxybate Dosages Greater Than 9 Grams in Study Participants With Narcolepsy.” It’s an interesting concept, because some patients still appear to need additional medication despite maxing out the currently approved sodium oxybate dose.
This study looked at a subset of individuals taking low-sodium oxybate at doses between 9 and 12 grams—9 grams being the current recommended maximum nightly dose. This came from what’s called the DUET cohort, which included 24 participants. The study evaluated the impact on sleepiness, narcolepsy symptom severity, suicide severity scores, treatment-emergent side effects from increasing doses, and importantly, any changes in sleep-related respiratory assessments.
In this group, the mean dose was 11 grams, and patients showed further improvements in symptoms—including lower Epworth Sleepiness Scale scores and reduced narcolepsy symptom severity. Treatment-emergent side effects such as headache, vomiting, and enuresis were reported but at low levels. AHI scores showed minimal change, with a delta of fewer than five events per hour. There were no reports of suicidal ideation or behaviors. So the takeaway is that in this small group, increasing low-sodium oxybate doses above 9 grams appeared to offer further benefit without a major safety concern.
Anita Shelgikar, MD: Thanks for that summary, Eric. I thought this was very interesting because when we manage patients using oxybate, safety is top of mind—especially around dosing, titration, and long-term monitoring. So the idea that we might safely manage symptoms and improve daytime alertness with doses higher than currently approved is really intriguing. I was curious to see that. I did catch that this was an interim analysis, so I’ll be interested to see how things look with the final data.
Eric Olson, MD: Yeah, a couple of questions came up for me. First, I believe the study period analyzed was pretty short—around two weeks—so it makes me wonder how these results would hold up over a longer timeframe. Another point is the effect on sleep-disordered breathing. About a third of participants had comorbid sleep apnea, but we don’t know whether they were being treated. If they were, that could have influenced the AHI data, which didn’t show much change.
A future abstract we’re going to cover looks at concurrent use of alerting agents in patients on oxybates. Clearly, oxybates alone aren’t always enough. So it’s interesting to see that further subjective improvement might be possible by pushing the dose, without a dramatic increase in side effects.
Anita Shelgikar, MD: Absolutely agree. And I think this really speaks to the importance of customizing and individualizing care. You mentioned patients with comorbid obstructive sleep apnea—when does that need to be reassessed? Does treatment for that comorbid sleep disorder need to be revisited to ensure it’s fully effective? I fully agree there are shades of gray and nuance as we manage these patients.