Fatigued but not sleepy? An empirical investigation of the differentiation between fatigue and sleepiness in sleep disorder patients in a cross-sectional study.

OBJECTIVE: Sleepiness and fatigue are common complaints among individuals with sleep disorders. The two concepts are often used interchangeably, causing difficulty with differential diagnosis and treatment decisions. The current study investigated sleep disorder patients to determine which factors best differentiated sleepiness from fatigue. METHODS: The study used a subset of participants from a multi-site study (n = 606), using a cross-sectional study design. We selected 60 variables associated with either sleepiness or fatigue, including demographic, mental health, and lifestyle factors, medical history, sleep questionnaires, rest-activity rhythms (actigraphy), polysomnographic (PSG) variables, and sleep diaries. Fatigue was measured with the Fatigue Severity Scale and sleepiness was measured with the Epworth Sleepiness Scale. A Random Forest machine learning approach was utilized for analysis. RESULTS: Participants' average age was 47.5 years (SD 14.0), 54.6% female, and the most common sleep disorder diagnosis was obstructive sleep apnea (67.4%). Sleepiness and fatigue were moderately correlated (r = 0.334). The model for fatigue (explained variance 49.5%) indicated depression was the strongest predictor (relative explained variance 42.7%), followed by insomnia severity (12.3%). The model for sleepiness (explained variance 17.9%), indicated insomnia symptoms was the strongest predictor (relative explained variance 17.6%). A post hoc receiver operating characteristic analysis indicated depression could be used to discriminate fatigue (AUC = 0.856) but not sleepiness (AUC = 0.643). CONCLUSIONS: The moderate correlation between fatigue and sleepiness supports previous literature that the two concepts are overlapping yet distinct. Importantly, depression played a more prominent role in characterizing fatigue than sleepiness, suggesting depression could be used to differentiate the two concepts.

Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the SEGUE study.

STUDY OBJECTIVES: Low-sodium oxybate (LXB; calcium, magnesium, potassium, and sodium oxybates; Xywav) contains the same active moiety as high-sodium oxybates (sodium oxybate [SXB; Xyrem] and fixed-dose sodium oxybate [Lumryz]), with 92% less sodium, and is approved in the US for treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy, and idiopathic hypersomnia in adults. Patients with narcolepsy have increased cardiovascular risk relative to people without narcolepsy. LXB's lower sodium content is recognized by the US FDA in the narcolepsy population as clinically meaningful in reducing cardiovascular morbidity compared with high-sodium oxybates. The Substitution of Equal Grams of Uninterrupted Xyrem to Xywav (SEGUE) study (NCT04794491) examined the transition experience of patients with narcolepsy switching from SXB to LXB. METHODS: Eligible participants were aged 18 to 80 years with narcolepsy type 1 or 2 on a stable SXB dose/regimen. After 2 weeks, participants transitioned gram-per-gram to LXB for 6 weeks, with opportunity for subsequent titration. Assessments included the Epworth Sleepiness Scale (ESS), Patient Global Impression of Change (PGIc), ease of switching medication scale (EOSMS), and forced preference questionnaire (FPQ). RESULTS: The study enrolled 62 participants at baseline; 60 transitioned to LXB and 54 completed the study. At baseline and end of the LXB intervention/early discontinuation, respectively, mean total doses were 8.0 and 8.0 g/night; mean ESS scores were 9.4 and 8.8. Most participants reported improvement (45%) or no change (48%) in narcolepsy symptoms on the PGIc, reported the transition to LXB was "easy" (easy, extremely easy, not difficult at all; 93%) on the EOSMS, and preferred LXB compared with SXB (79%) on the FPQ, most commonly due to the lower sodium content. CONCLUSIONS: Most participants switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition process was easy. Effectiveness of oxybate treatment was maintained on LXB, and most participants preferred LXB to SXB. No new safety or tolerability issues were identified. CLINICALTRIALREGISTRATION: Registry: ClinicalTrials.gov; Name: An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy; URL: https://classic.clinicaltrials.gov/ct2/show/NCT04794491; Identifier: NCT04794491.

Dosing and transition characteristics in people with narcolepsy transitioning from sodium oxybate to low-sodium oxybate: Data from the real-world TENOR study.

OBJECTIVE: The Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR) study assessed the real-world experience of people with narcolepsy switching from sodium oxybate (SXB) to low-sodium oxybate (LXB; 92 % less sodium than SXB). METHODS: TENOR is a patient-centric, prospective, observational, virtual-format study. Eligible participants included US adults with narcolepsy transitioning from SXB to LXB (±7 days from LXB initiation). Longitudinal data were collected from baseline (taking SXB) through 21 weeks post-transition. RESULTS: TENOR included 85 participants with narcolepsy (type 1, n = 45; type 2, n = 40). Mean (SD) age was 40.3 (13.0) years; the majority (73 %) were female and White (87 %). At study completion, wake-promoting agents were the most common concomitant medications (47 %). Mean (SD) SXB treatment duration was 57.8 (52.1) months; 96 % took SXB twice nightly. After transitioning, 97 % continued on twice-nightly regimens. Mean (SD) dose of both total nightly SXB (n = 85) and baseline LXB (n = 84) was 7.7 (1.5) g; SXB-LXB dose conversions at baseline were gram-for-gram in 87 % of participants. The mean final total nightly dose of LXB was 7.9 g. The most common participant-reported reasons for transitioning included lower sodium content for improved long-term health (93 %), physician recommendation (47 %), to avoid cardiovascular issues (39 %), to avoid side effects (31 %), and to improve control of narcolepsy symptoms (18 %). CONCLUSION: Most participants transitioned from SXB to LXB using a gram-for-gram strategy. The most commonly cited reason for transition was long-term health benefits due to lower sodium.