Fatigue and Objective Sleepiness Show Distinct Profiles in Patients With Obstructive Sleep Apnea

A recently published cross-sectional study reported that fatigue, measured by Fatigue Severity Scale (FSS), and objective excessive daytime sleepiness (EDS), measured by the mean sleep latency (MSL) on the multiple sleep latency test (MSLT), were uncorrelated in patients with obstructive sleep apnea (OSA). However, the findings, published in Sleep Medicine, showed that each OSA symptom contributed similarly to subjective EDS.¹

Using a cohort of 603 patients from the US and Germany, findings showed that the MSL was not correlated with the FSS overall (r = −.008, P = .85) or by each site. In contrast, results revealed that the FSS and the Epworth Sleepiness Scale (ESS) demonstrated a mild correlation (r = .28, P <.001), with slightly higher correlation in the US cohort (r = .38) compared with the German cohort (r = .25). In addition, authors noted that the ESS and MSL were modestly inversely correlated (r = −.23, P <.001).

“Our finding that subjective EDS is a mix of EDS and fatigue is important for a different reason. We have demonstrated that even if one could reduce the variability of ESS by, for instance, computing a sample mean ESS over a population of patients with OSA, the information in that sample mean about symptoms of OSA would still be an uninterpretable mix of information about two uncorrelated symptoms, objective EDS and fatigue,” senior author Avram R. Gold, MD, associate professor of medicine at the Stony Brook University Sleep Disorders Center, and colleagues wrote.¹

In this study, investigators evaluated the relationship between fatigue and both objective and subjective EDS using the FSS in patients with OSA. The analysis included 80 patients from Somnolab Dortmund in Germany and 223 patients from the Stony Brook University Sleep Disorders Center in the US. The German cohort comprised of patients with a new OSA diagnosis who completed the FSS, ESS, and MSL, excluding those with prior OSA treatment or restless legs syndrome. Authors noted that the recruitment in the German cohort occurred from October 2019 to April 2023 and the US cohort represented a subset of a previously reported series of 302 untreated patients with OSA evaluated from January 2008 through October 2012.^2,3

READ MORE: Sleep Duration and Psychological Distress as Key Drivers of EDS, Study Shows

“The etiology of fatigue in patients with OSA remains poorly understood. Fatigue is sometimes attributed to sleep fragmentation, supported by evidence that CPAP therapy can partially relieve it. Objective EDS is also widely ascribed to the same mechanism. Yet, despite sharing this proposed pathology, our data demonstrate that the two symptoms are completely uncorrelated,” Gold et al noted.¹ “This paradox highlights a critical gap: if both fatigue and EDS stem from sleep fragmentation, how do they remain independent of one another?"

The study population was predominantly middle-aged and men. Authors noted that German patients were near the threshold for obesity, whereas US patients were classified as obese. Overall, approximately half of patients demonstrated clinically significant objective EDS, with similar rates at each site. In contrast, about one-third of patients reported subjective EDS, with a lower prevalence in Germany (27.6%) compared with the US (42.1%). Furthermore, the mean FSS scores were approximately 4 across the overall population and at each site, with at least half of patients at each site experiencing clinically significant fatigue.

All told, a limitation of the current study is its design as a clinical series, with inclusion based solely on the availability of the ESS, FSS, and MSLT and minimal additional restrictions. Researchers reported that the study also lacked an objective measure of fatigue, as no widely accepted objective assessment exists. Although the FSS has demonstrated acceptable validity and reproducibility in other conditions, authors noted that its performance has not been specifically evaluated in patients with obstructive sleep apnea.

“One proposed explanation for CPAP therapy decreasing both fatigue and EDS among patients with OSA without decreasing sleep fragmentation being the sole mechanism is that sleep-disordered breathing generates a form of biologic stress in the brain, producing fatigue independently of sleepiness. In previous work, we have suggested that fatigue in OSA results from this biologically generated neural stress triggered by apneas, hypopneas, and even milder inspiratory airflow limitation. In contrast, sleep fragmentation arising from arousals associated with apneas and hypopneas produces sleepiness through a separate mechanism.”

REFERENCES
1. Gold MS, Stoohs RA, Gold AR. Objective versus subjective excessive daytime sleepiness in OSA: Quantifying the impact of fatigue. Sleep Med. Published online February 25, 2026. doi:10.1016/j.sleep.2026.108867
2. Amdo T, Hasaneen N, Gold MS, Gold AR. Somatic syndromes, insomnia, anxiety, and stress among sleep disordered breathing patients. Sleep Breath. 2016;20(2):759-768. doi:10.1007/s11325-015-1296-6
3. Gold MS, Amdo T, Hasaneen N, Gold AR. Somatic arousal and sleepiness/fatigue among patients with sleep-disordered breathing. Sleep Breath. 2016;20(2):749-758. doi:10.1007/s11325-015-1294-8