Once-Nightly Oxybate in Narcolepsy: Real-World Outcomes Primary Care Should Know

Narcolepsy affects an estimated 1 in 2,000 people in the United States and is associated with significant functional impairment extending well beyond excessive daytime sleepiness. Depression and anxiety co-occur in at least 40% of patients, and many require stimulant therapy that carries risks of tolerance, withdrawal, and potential long-term cardiovascular consequences. These comorbidities complicate management and highlight the need for real-world evidence on how available therapies perform outside the controlled conditions of randomized trials.

The REFRESH trial was designed to address that gap. The prospective, observational study enrolled patients with type 1 or type 2 narcolepsy who were initiating once-nightly sodium oxybate (Lumryz) or switching from a twice-nightly oxybate regimen. Participants completed the Epworth Sleepiness Scale, the Narcolepsy Severity Scale, the Sheehan Disability Scale, and a 7-item symptom questionnaire rating the severity of depression, anxiety, brain fog, and fatigue at baseline and again at 16 weeks. More than 50% of enrollees were already on stimulant therapy and antidepressants at study entry, a population more representative of real-world clinical practice than participants in typical randomized controlled trials.

At 16 weeks, both oxybate-naive patients and switchers showed improvements in Epworth scores trending toward normalization at 10 or below. Narcolepsy Severity Scale scores also improved, and the Sheehan Disability Scale demonstrated significant gains in social, work, and family functioning. Stimulant use fell by approximately 50% on average, and patients reported trends toward improvement across all 7 symptom domains, including depression, anxiety, and brain fog. Caregiver-reported outcomes reflected similar gains.

Laura B. Herpel, MD, sleep physician at Bogan Sleep Consultants and adjunct assistant professor at the Medical University of South Carolina, presented these findings at SLEEP 2026. Below, Herpel shares her perspective on what the REFRESH data means for clinicians managing narcolepsy in practice.