Survey findings suggest fatigue remains widespread and debilitating across narcolepsy and idiopathic hypersomnia, even among patients taking medications.
By Risa Kerslake, RN, BSN
Fatigue is a symptom commonly reported by patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), and it differs from excessive daytime sleepiness. Patients can experience excessive daytime sleepiness and fatigue separately.
However, past research has been based largely on qualitative, anecdotal evidence, according to Michael Doane, PhD, the head of health economics and outcomes research at Alkermes. This gap prompted Doane and co-investigators to conduct a large-scale survey study to better characterize symptoms such as fatigue and cognitive impairment. “One of the things that stood out was how prevalent these symptoms are and how consistent that is across the different populations we looked at,” Doane says.
Doane and his team presented results from the ASPIRE survey study at SLEEP 2026. The survey study examined the real-world burden of fatigue in 366 adults with a diagnosis of NT1, NT2, and IH. Fatigue severity was measured using the PROMIS-Fatigue Short-Form 6a, with participants grouped by T-score into mild-to-severe (55 or above) and normal (below 55).
Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and health-related quality of life was evaluated using the EQ-5D-5L and EQ-Visual Analogue Scale. Many participants were receiving stimulant and non-stimulant wake-promoting agents at the time of the survey.
The majority of participants (91%) fell into the mild-to-severe fatigue category. Compared to those with normal fatigue, participants with mild-to-severe fatigue showed significantly higher rates of work impairment (59% versus 21%) and activity impairment (66% versus 28%), along with lower health-related quality of life scores.
These results were consistent across NT1, NT2, and IH subgroups, which suggests that fatigue is an underrecognized and substantial unmet need across patients with hypersomnia disorders that current treatments may not adequately address.
“There’s a need to continue looking into new treatment options, and to continue including those symptoms as key outcome measures when it comes to understanding treatment benefit,” Doane says.
One limitation of survey research is that these studies typically enroll patients who are well-connected, healthy, and interested enough to participate in research, which can lead to selection bias. “Individuals who aren’t healthy or doing well related to their condition are unlikely to participate in this kind of research. If anything, we’re probably underestimating just how prevalent and how bothersome these symptoms are,” explains Doane.
Despite participants taking daytime medications for their symptoms, they still describe the impact fatigue has on their lives. It’s one of the reasons for Alkermes’ alixorexton program, an orexin receptor 2 agonist under development in phase 3 Brilliance trials for NT1 and NT2 and a phase 3 Vibrance-3 trial for IH.
“As we look toward the future, we’re excited to bring a potential treatment to patients that can address multiple symptoms, and the symptoms that may not be adequately addressed with some of the medications to date,” says Doane.
Clinicians should consider symptoms beyond excessive daytime sleepiness across patient conditions, given how prevalent symptoms such as fatigue emerged from the study. “It’s thinking about more than that hallmark symptom, knowing that patients experience many other symptoms that are also just as bothersome,” says Doane.
Reference
Michael Doane, Jane Lazar Tucker, Kristen McCausland, et al. 0699 Real-world experience and impact of fatigue in narcolepsy and idiopathic hypersomnia: Survey results from the ASPIRE study. Sleep. May 2026 (suppl_1);49:A311-2.
