Chenlu Gao, PhD, from Massachusetts General Hospital and Harvard Medical School

Chenlu Gao, PhD

HCPLive Five at SLEEP 2025 

 SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies,

 from June 9 – 11th in Seattle, Washington, to share new sleep medicine data.

As a part of HCPLive’s on-site coverage, the editorial team conducted > 15 interviews on various topics, from new pharmacotherapy treatments for OSA and AI in sleep medicine to changes to the restless legs syndrome (RLS) guidelines and the association between napping and mortality risk in older adults.

In this edition of the HCPLive Five, the team captured the top 5 interviews at the meeting, featuring research on a VeNS device for insomnia and PTSD, latest pharmacotherapy developments for sleep apnea, new RLS guidelines, the link between naps and mortality risk, and AD109 for obstructive sleep apnea (OSA).

VeNS Device Improves PTSD, Insomnia Symptoms in RCT, with Peter Colvonen, PhD

Peter Colvonen, PhD, an associate clinical professor at the University of California, San Diego, presented results from a randomized controlled trial showing that vestibular nerve stimulation (VeNS) significantly improved PTSD and insomnia symptoms. The 12-week trial involved over 380 adults with PTSD, many of whom face years-long waits for 1-on-1 therapy.

VeNS, a non-invasive, at-home device, led to significantly greater reductions in PTSD and Insomnia Severity Index scores compared to a sham. Colvonen emphasized its potential as an interim solution for patients stuck on long waitlists, highlighting VeNS as a scalable option to stabilize symptoms until gold-standard care becomes available.

Latest Pharmacotherapy Developments for Sleep Apnea, with Danny Eckert, PhD

Danny Eckert, PhD, a professor at Flinders University, highlighted emerging pharmacotherapies for obstructive sleep apnea (OSA), addressing both anatomical and non-anatomical causes. The FDA-approved GLP-1 agonist tirzepatide helps reduce OSA in obese patients through weight loss.

For non-obese individuals, AD109, a combination of aroxybutynin and atomoxetine, showed promise in a phase 3 trial, resolving OSA in 25% of patients. Eckert also discussed potassium channel blockers that reset airway reflexes and acetazolamide, which lowers loop gain and reduces OSA severity. These advances mark a shift toward personalized, drug-based OSA treatments, especially for patients who struggle with traditional therapies like CPAP.

RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

John Winkelman, MD, PhD, chief of the sleep disorders clinical research program at Massachusetts General Hospital, discussed the AASM’s updated restless legs syndrome (RLS) guidelines, which now advise against routine use of dopamine agonists due to high augmentation risk. Up to 50% of patients on these drugs may experience symptom worsening over five years. The guidelines recommend iron therapies and alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) instead.

Winkelman emphasized identifying and managing exacerbating factors like antidepressants, antihistamines, or sleep apnea. He advises a slow, careful taper of dopamine agonists over 6–12 months, warning patients of temporary worsening but long-term improvement once off the medication.

Naps at Noon Linked to Mortality Risk in Older Adults, with Chenlu Gao, PhD

Chenlu Gao, PhD, from Massachusetts General Hospital and Harvard Medical School, presented findings linking longer, irregular, and early afternoon naps to increased all-cause mortality in middle-to-older adults. Using UK Biobank data from over 86,000 participants, the study found that greater nap duration, high day-to-day variability, and naps between 11 am–3 pm were associated with higher mortality risk over an 8-year follow-up.

Gao emphasized the study was observational and not causal—napping patterns may reflect underlying health issues like sleep disorders or chronic illness. She advised clinicians to address root causes of excessive napping rather than eliminating naps entirely.

AD109 Improves OSA in Phase 3 SynAIRgy Trial, With Patrick Strollo, MD

Patrick Strollo, MD, from the University of Pittsburgh Medical Center, presented phase 3 SynAIRgy trial results showing that AD109, a once-daily oral neuromuscular modulator, significantly improved obstructive sleep apnea (OSA). In the 26-week trial of 646 participants intolerant of CPAP, AD109 reduced apnea-hypopnea index (AHI) by 55.6% and improved oxygenation measures. More than half of participants had reduced OSA severity, and 22.3% achieved full disease control (AHI < 5).

AD109, a first-in-class combination of aroxybutynin and atomoxetine, works by enhancing upper airway muscle tone during sleep. Apnimed plans to submit an FDA application in early 2026, with additional phase 3 data expected later in 2025.

Articles

Sleep experts gathered at SLEEP 2025 to discuss advancements in sleep medicine, including new treatments and guidelines. Key topics included a VeNS device for PTSD and insomnia, pharmacotherapy for sleep apnea, updated RLS guidelines, and the link between napping and mortality risk. The VeNS device showed promise in reducing PTSD and insomnia symptoms, while new pharmacotherapies like AD109 and tirzepatide offered hope for OSA patients. Updated RLS guidelines advised against dopamine agonists, and research linked irregular naps to increased mortality risk, emphasizing the need to address underlying health issues.

Check out the top 5 interviews from SLEEP 2025.

A study found that frequent, longer, and irregular daytime 

, especially around noon or in the early afternoon, are linked to a greater mortality risk in middle-to-older adults.

Chenlu Gao, PhD, from Massachusetts General Hospital and Harvard Medical School, presented this study at 

SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies

, from June 8 to 11 in Seattle. HCPLive sat down with Gao during the meeting to discuss the relationship between specific napping patterns, such as occasional or habitual napping, and a greater mortality risk in middle-to-older adults.

“We did not specifically examine each specific cause of death, and I think that's [a] great direction for future research in terms of the strength of the associations,” Gao said. “They were statistically significant, but relatively small in magnitude, meaning that napping patterns only explained a small proportion of mortality risk.”

Gao and colleagues sought to determine whether actigraphy-measured objective daytime napping behaviors predict all-cause mortality in middle-to-older aged adults in the US. Leveraging UK Biobank data, the study included 86,565 participants (57% females) with a mean baseline age of 63 years. Participants did not have a shiftwork history.

Participants completed 7-day actigraphy monitoring and had data linked to mortality registries. Investigators used the Cole-Kripke algorithm to identify daytime sleep episodes from actigraphy and tracked the following metrics: mean nap duration between 9 am – 7 pm, intra-individual variability across days in nap duration, and times of any 2-hour naps between the hours of 9 – 11 am, 11 am – 1 pm, 1 – 3 pm, 3 – 5 pm, and 5 – 7 pm.

The team assessed the associations between napping patterns and all-cause mortality through Cox proportional hazard models, adjusted for demographics, body mass index (BMI), smoking, alcohol consumption, comorbidities, nighttime sleep duration, and chronotype.

The study found mean nap duration was 0.40 hours/day (IQR, 0.19 – 0.77), and intra-individual variability of nap duration was 0.39 hours (IQR, 0.19 – 0.67). When it came to napping behaviors, 34% of participants took naps between 9 – 11 am, 10% between 11 am – 1 pm, 14% between 1 pm – 3 pm, 19% between 3 pm – 5 pm, and 22% between 5 pm – 7 pm.

During the 8-year follow-up, 3.4% of participants died, with an average survival time of 4.19 (range, 0.03 – 8.15) years after baseline. The analysis showed that longer nap duration (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.16 – 1.24;

 < .0001), greater intra-individual variability (HR, 1.14; 95% CI, 1.10 – 1.18; 

 < .0001), and more naps between 11 am – 1 pm (HR, 1.07; 95% CI, 1.03 – 1.11; 

 = .0005) and between.1 – 3 pm (HR, 1.07; 95% CI, 1.03 – 1.12; 

Gao noted that, despite these findings, the analysis did not provide direct evidence that 2-hour naps or early afternoon naps pose a mortality risk, since this study is merely observational and did not show causation. However, the study did demonstrate the association between certain napping behaviors and an increased mortality risk.

“We think it's more likely that napping patterns reflect underlying health conditions,” Gao said. “For example, excessive and irregular napping could be a result of poor nighttime sleep, sleep disorders, circadian disruption, or other health conditions, such as cardiovascular disease, metabolic disorders, mood disorders, or early neurodegeneration. I think if clinicians were to do any interventions, they should be targeting the causes of excessive napping rather than simply trying to eliminate napping itself.”

Chenlu Gao, Ruixue Cai, Xi Zheng, Lei Gao, Kun Hu, Peng Li, 0350 Objectively-Assessed Napping Behaviors Predict Mortality in Middle-to-Older Aged Adults, 

, Volume 48, Issue Supplement_1, May 2025, Page A152, 

https://doi.org/10.1093/sleep/zsaf090.0350

Videos

A study presented at SLEEP 2025 found longer and more variable napping patterns are associated with increased all-cause mortality in middle-to-older aged adults.
