Excessive Daytime Sleepiness In Patients Research Articles

Comparative efficacy, safety and benefit/risk of alerting agents for excessive daytime sleepiness in patients with obstructive sleep apnoea: a network meta-analysis

Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640. Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150mg; effect size [ES]=0.66 [95% CI: 0.36, 0.96]), pitolisant (20mg; ES=0.66 [95% CI: 0.44, 0.88]), and modafinil (200mg; ES=0.54: [95% CI: 0.33, 0.74]); 400mg; ES=0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200mg, modafinil 400mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400mg and modafinil 200mg for benefit-risk ratio. Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Bioprojet.

The role of large muscle movements on excessive daytime sleepiness in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a heterogeneous disorder requiring personalized diagnostic approaches. Restless sleep and excessive daytime sleepiness (EDS) frequently accompany OSA, and are mainly linked to sleep fragmentation secondary to apneas and/or hypopneas. In this study, we aimed to analyze the characteristics of LMMs in OSA and to evaluate interrelationship between LMMs and EDS. Untreated-naïve adult OSA patients, with vs. without EDS were prospectively enrolled. Patients with comorbid neurological/psychiatric diagnosis, usage of drugs/substances known to affect sleep and positive airway pressure therapy were excluded. Routine evaluation of video-polysomnography was followed by LMM scoring. LMMs were compared between OSA with vs. without EDS, and correlations of LMMs with ESS scores and macrostructural sleep parameters were analyzed. Sixty patients were included (median age 43.5 [37.0] years, %78.3 men); 17 had EDS with Epworth Sleepiness Scale (ESS) ≥ 10 (28.3%). Total LMM index in total sleep time (TST) was 7.9 [20.6]. Total LMM index in TST (p = 0.048) and N1 (p = 0.020), and arousal-related LMM index in TST (p = 0.050) and N1 (p = 0.026) were higher in OSA with EDS than those without EDS. ESS scores were positively correlated with total (r = 0.332,p = 0.028) and arousal-related (r = 0.338,p = 0.025) LMM indexes in N1, and abnormal respiratory event-related LMM indexes in N1 (r = 0.440,p = 0.003) and N3 (r = 0.293,p = 0.050) after correction for age, sex, body-mass-index and apnea-hypopnea index. Our study demonstrated that LMMs were more frequent in OSA with EDS than those without EDS. This may have broad implications for the mechanisms of motor restlessness and residual sleepiness in OSA and warrants larger-scale, long-term follow-up studies. No clinical trial registration due to the observational design of the study.

Comparison of the effectiveness of modafinil and methylphenidate in treatment of excessive daytime sleepiness in patients with Parkinson's disease.

Background: A large percentage of patients with Parkinson's disease (PD) suffer from excessive daytime sleepiness (EDS). This study aims to compare the effectiveness of modafinil and methylphenidate on EDS and side effects. Methods: Fifty nine patients with PD and EDS [Epworth Sleepiness Scale (ESS) more than 9] were recruited in a double-blind placebo controlled trial. Twenty-two patients received modafinil 200 mg daily, twenty-six patients received methylphenidate 10 mg daily, and 11 patients received placebo for 6 weeks. Pittsburgh Sleep Quality Index (PSQI) and ESS were filled out at baseline and 6 weeks later. Results: There was no significant difference in demographics, PSQI, and ESS variables at baseline. The mean of ESS scores decreased significantly in modafinil (17.36 ± 5.05 vs. 10.55 ± 4.62, P < 0.001) and methylphenidate (16.27 ± 5.40 vs. 12.23 ± 6.28, P < 0.001) groups after 6-week trial, compared with control group (14.27 ± 4.49 vs. 14.09 ± 4.46, P = 0.710). The effectiveness of modafinil and methylphenidate on improving daytime sleepiness and night sleep of patients was not significantly different. Conclusion: Both modafinil and methylphenidate were effective drugs in improving EDS and quality of sleep without significant difference in efficiency and side effects.

Excessive daytime sleepiness in patients with obstructive sleep apnea: a risk assessment.

Excessive daytime sleepiness in patients with obstructive sleep apnea: a risk assessment.

Effects of high-intensity interval training on subjective sleep quality and daytime sleepiness in patients with obstructive sleep apnea: A secondary analysis from a randomized controlled trial

This study aimed to verify the effect of 12 weeks of HIIT on the perceived sleep quality and excessive daytime sleepiness in patients with obstructive sleep apnea (OSA). For this, a secondary analysis of a randomized controlled trial, including 36 adults with moderate-severe OSA (19 males; 52.2 ± 9.8 years; body mass index = 34.2 ± 5.8; AHI = 42.0 ± 22.9 e/h) was performed. Participants were randomly assigned to HIIT [5 periods of 4 min of walking or running on a treadmill at 90–95 % of maximum heart rate (HRmax) interspersed with 3 min of walking at 50–55 % of HRmax performed three times per week for 12 weeks] or a control group (CG; stretching exercises performed two times per week for 12 weeks). Specific domains of subjective sleep quality and EDS were assessed at baseline and post 12 weeks. Generalized estimated equation were used to verify between groups and times differences. There were no group × time interactions for the domains sleep duration (0.416), sleep efficiency (0.198), sleep disturbance (0.523), and sleep medications (0.915). However, significant group × time interactions were observed for global sleep score (0.022), and for the domains sleep quality (0.001), sleep latency (0.029), and daytime dysfunction (0.012). In addition, there was a significant group × time interaction for EDS (HIIT = −3.4 ± 0.9; CG change = −1.0 ± 1.0; p = 0.023). Thus, in patients with OSA, 12 weeks of HIIT improves perceived sleep quality and daytime sleepiness.

Development and evaluation of the Indian Sleepiness Scale to assess excessive daytime sleepiness in patients with Obstructive Sleep Apnea

BackgroundExcessive daytime sleepiness (EDS), a cardinal symptom of obstructive sleep apnea (OSA) is assessed using Epworth Sleepiness Scale (ESS). Some limitations of ESS include graded responses, inapplicable situations and equal scores for active and passive situations. To overcome these limitations, we developed a novel sleepiness scale and evaluated its performance in patients with OSA. MethodsThe study was executed in multiple phases. After determining applicability of items in the ESS, a 6-item questionnaire was developed comprising OSA symptoms and self-reported ‘sleepy’ situations, dichotomized responses and weighted scoring. After content and face validation by experts, the scale was tested for applicability and its performance was compared with ESS in patients with suspected OSA. ResultsIn phase I, applicability of ESS was tested in 189 participants, of whom 98 (51.8 %) participants found multiple items inapplicable.In phase II, 34 self-reported sleepy situations from 200 participants were narrowed down to a 6-item questionnaire, based on expert validation. This scale was named the Indian Sleepiness Scale (ISS) and was tested for applicability in phase III in 226 participants from diverse literacy backgrounds, who found all situations applicable.In phase IV, ISS and ESS were administered to 335 patients with suspected OSA. OSA was confirmed on polysomnography in 294 (87.7 %) patients. A cut-off score of ≥6 was derived for ISS; at this cut-off score, the ISS which was more sensitive than ESS (71.1 % vs 43.2 %). ConclusionsThe Indian Sleepiness Scale was found to be widely applicable and more sensitive than ESS for sleepiness evaluation in patients with OSA.

Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study.

Low-sodium oxybate (LXB; calcium, magnesium, potassium, and sodium oxybates; Xywav) contains the same active moiety as high-sodium oxybates (SXBs; SXB [Xyrem] and fixed-dose SXB [Lumryz]), with 92% less sodium, and is approved in the United States 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 United States Food and Drug Administration in the narcolepsy population as clinically meaningful in reducing cardiovascular morbidity compared with SXBs. The Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study (NCT04794491) examined the transition experience of patients with narcolepsy switching from SXB to LXB. Eligible participants were aged 18-80 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, Patient Global Impression of change, Ease of Switching Medication Scale, and Forced Preference Questionnaire. 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 Epworth Sleepiness Scale scores were 9.4 and 8.8. Most participants reported improvement (45%) or no change (48%) in narcolepsy symptoms on the Patient Global Impression of change, reported the transition to LXB was "easy" (easy, extremely easy, not difficult at all; 93%) on the Ease of Switching Medication Scale, and preferred LXB compared with SXB (79%) on the Forced Preference Questionnaire, most commonly due to the lower sodium content. 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. 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. Macfadden W, Leary EB, Fuller DS, Kirby MT, Roy A. Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study. J Clin Sleep Med. 2024;20(9):1467-1477.

0970 Real-world Use of Solriamfetol for Excessive Daytime Sleepiness in Patients Reporting Anxiety or Depression

0970 Real-world Use of Solriamfetol for Excessive Daytime Sleepiness in Patients Reporting Anxiety or Depression

Hypocretin-1/orexin-A, sleep and excessive daytime sleepiness in patients with nonconvulsive status epilepticus: A cross-sectional cohort study

Background and objectivesNonconvulsive status epilepticus (NCSE) manifests as a change in mental status without a coma (NCSE proper) or comatose NCSE. Hypocretin-1/orexin-A (H/O) is involved in alertness and sleep maintenance. Sleep impairment and excessive daytime sleepiness (EDS) have a negative impact on cognitive functions and activities of daily living (ADL). MethodsPatients meeting the NCSE criteria underwent cerebrospinal fluid and brain magnetic resonance imaging examinations, polysomnographies (PSG), multiple latency sleep tests (MSLT), and completed Epworth Sleepiness Scale (ESS). Montreal Cognitive Assessment was used to evaluate cognitive functions, and the Barthel Index was used to assess ADL in the acute phase (V1) and three months follow-up (V2). ResultsFrom May 2020 to May 2023, we enrolled 15 patients, eight (53.3 %) women, with a median age of 69 (14) years. The median H/O CSF concentration was 250 (63.6) pg/ml; however, only three CSF samples (20 %) decreased below the borderline concentration of 200 pg/ml. Fourteen out of 15 patients (93.3 %) completed the PSG study. The median of wakefulness after sleep onset was 167 (173.5) min, sleep efficiency (SE) was 62.9 (63) %, sleep latency (SL) was 6 (32) min, REM sleep was 2.85 (7.2) %, and REM first episode latency was 210.5 (196.5) minutes. The medians of the stages N1 NREM were 4.65 (15) %, N2 NREM 68.4 (29.9) %, and N3 NREM 21.8 (35.5) %. MSLT mean latency was 7.7 (12.6) minutes. A significant negative correlation exists between H/O CSF concentrations and the stage N1 NREM (rs = −0.612, p = 0.02), and the proportion of cumulative sleep time with oxygen saturation below 90 % in total sleep time (TST) t90 (rs = −0.57, p = 0.03). MSLT had significant negative correlation with TST (rs = −0.5369, p = 0.0478), with SE (rs = −0.5897, p = 0.0265), with apnea-hypopnea index (rs = −0.7631, p = 0.0002) and with deoxygenation index (rs = −0.8009, p = 0.0006). A positive correlation exists between MSLT and SL (rs = 0.6284, p = 0.0161) and between ESS and t90 (rs = 0.9014, p = 0.0004). The correlation between H/O CSF concentrations and EDS, cognitive performance, and ADL was not proved. ConclusionsPatients after NCSE exhibited sleep impairment and excessive daytime sleepiness. Hypocretin-1/orexin-A concentrations decreased only in 20 % of these cases.

Excessive Daytime Sleepiness in Patients With Hypertension: A Systematic Review.

We must remember that there are many subclinical cases of obstructive sleep apnea (OSA), even if the patient or family members typically become aware of it through symptoms such as snoring and excessive daytime sleepiness (EDS). EDS is a common symptom among hypertensive patients.This interesting and remarkable systematic review aims to comprehensively survey the current literature on the prevalence and association of EDSamong hypertensive patients.PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI (Rayyan Systems Inc., Cambridge, MA) was employed throughout this comprehensive process.This review included nine studies with a total of 58,517 patients, and 34,398 (58.8%) were males. EDS prevalence among hypertensive patients ranged from 12.1% to 88.3%. This reviewstated that individuals with hypertension (HTN) had EDS that was worse than that of patients with normotension. In one of the studies included in this analysis, sympathovagal imbalance was noted alongside EDS and HTN. Older age, primary education, being overweight, working, obesity, depression, and having had the condition for longer are all associated with EDS in HTN patients.

Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary.

Narcolepsy is associated with disrupted nighttime sleep (DNS). Sodium oxybate (SXB; Xyrem®), administered twice nightly, is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7years or older with narcolepsy. Recently, low-sodium oxybate (LXB, Xywav®; for people 7years of age and older), which contains 92% less sodium than SXB and is dosed twice nightly, and sodium oxybate for extended release (SXB-ER; Lumryz™; for adults), which contains equal sodium to SXB and is dosed once nightly, have also been approved to treat cataplexy or excessive daytime sleepiness in narcolepsy. This paper reviews the evidence regarding the overall impact of oxybate administration, and impact of different oxybate dosing regimens (once nightly, SXB-ER; twice nightly, SXB), on DNS in narcolepsy utilizing polysomnographic data from five clinical trials (three assessing SXB in adults [referred to here as SXB trials1, 2, and 3], one assessing SXB in children [referred to as the pediatric SXB trial], and one assessing SXB-ER in adults [REST-ON]). Both once-nightly and twice-nightly oxybate regimens similarly improved symptoms of DNS. Regardless of dosing regimen, people with narcolepsy treated with oxybate experience roughly 42-53 arousals and 9-38 awakenings each night, with one of these awakenings on twice-nightly oxybate being due to the second dosing requirement in studies of SXB. Additionally, for SXB, but not SXB-ER, polysomnographic data has been analyzed by half of the night, demonstrating a greater positive impact on sleep architecture in the second half of the night, which might be related to its nonlinear pharmacokinetic profile. We conclude that while once-nightly and twice-nightly oxybate dosing regimens differ in their pharmacokinetic profiles, both improve DNS in patients with narcolepsy to a similar degree.

Positive Pressure Ventilation Treatment Based on Daytime and Night-time Titration in Patients with Obesity Hypoventilation Syndrome: A Randomized Controlled Trial.

Objectives The aim of the present study was to investigate the improvements of gas exchange and excessive daytime sleepiness in patients with obesity hypoventilation syndrome (OHS) in daytime and night-time split polysomnography (DSPSG and NSPSG). Materials and Methods In the present randomized controlled trial, patients with OHS were enrolled in two DSPSG (51 patients) and NSPSG (50 patients) groups in the Bamdad respiratory and sleep research center in Isfahan, Iran. In both groups, the diagnostic polysomnography (PSG) and titration were conducted in one session according to the guidelines of NSPSG. SpO2, PaCO2, and the Epworth Sleepiness Scale (ESS), were measured initially and 12 weeks after treatment. Furthermore, the PSG parameters and the type of treatments for the two groups were recorded and analyzed. Results A total of 101 OHS patients (age: 62.02 ± 12.4 year old; 61 females [60.4%]) were evaluated. There were no significant differences regarding BMI, gender, and AHI between groups ( p > 0.05). Primary SpO2, PaCO2, and ESS were not significantly different between the two groups. After 12 weeks of treatment by continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP), there were significant improvement of SpO2, PaCO2, and ESS score ( p < 0.001). The amount of change of these variables was not different between groups. Among all variables, only the lower SpO2 and higher PaCO2 were associated with response to BiPAP. Discussion There were no significant differences in the number of changes of SpO2, PaCO2, and ESS by treatment in the DSPSG and NSPSG groups. Therefore, DSPSG may be considered as a valuable alternative method for the diagnosis and titration in OHS patients. Clinical Trials IRCT20170512033930N2.

Factors correlated with excessive daytime sleepiness in patients with Parkinson's disease: A polysomnography study.

To explore the factors correlated with excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD). A total of 239 PD patients were divided into two groups based on the presence of EDS (Epworth Sleepiness Scale score≥10) (PD-EDS vs. PD-non-EDS). Participants underwent an extensive assessment to determine demographic features, disease severity, polysomnography characteristics, and nonmotor symptoms. Of the 239 patients, 56 patients (23.4%) were classified as having PD combined with EDS. Binary logistic regression analysis showed that fatigue (Fatigue Severity Scale [FSS] score ≥4) (odds ratio [OR] [95% CI]=4.897 [2.376-10.095], p<.001) and the respiratory-related microarousal index (OR [95% CI]=2.063 [1.085-3.923], p=.027) were independent risk factors for EDS in PD patients. A priori-determined stratified analysis showed that after adjustment for confounding factors, the association of the respiratory-related microarousal index with EDS was significant (OR=4.404, 95% CI 1.673-11.592, p trend=.036) in patients with respiratory arousal index scores in the highest quintile compared with those with scores in the lowest quintile. Our data revealed a close association among the respiratory-related microarousal index, FSS scores, and EDS. It can be speculated that fragmented sleep and pathological abnormalities of the central nervous system resulting in changes in arousal are major influencing factors of EDS in PD.

Effect of Subthalamic Nucleus Deep Brain Stimulation Treatment on Non-motor Symptoms and Sleep Quality in Parkinson’s Disease Patients

Aim: To evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS), sleep quality, and excessive daytime sleepiness in patients with Parkinson’s Disease (PD). Method: Sixteen PD patients, who had undergone bilateral STN-DBS surgery were enrolled. The patients were assessed at the baseline and 12 months after surgery using the Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire (PDQ-39), Beck Depression Inventory-II (BDI), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Non-Motor Symptom Questionnaire (NMS-Quest). Results: The mean age of the patients at the time of surgery was 53.5±3.6 years. There were significant improvements in the levodopa-equivalent daily dose, UPDRS-part-II, UPDRS-part-III, and UPDRS-part-IV at 12 months post-DBS surgery. The NMS-Quest total score at baseline was correlated with the disease duration of the patients (p=0.005 R:0.66). The PSQI score at baseline was significantly associated with a high total UPDRS and HADS score (p=0.03, p=0.004 respectively). There were no significant differences in terms of NMS-Quest total and subdomains thereof and PSQI total score and subdomains thereof, UPDRS-part I, BDI-II and HADS scores between baseline and 12 months post-DBS surgery (p&amp;gt;0.05 for all of them). Conclusion: STN-DBS surgery did not change subjective sleep quality, excessive daytime sleepiness, and NMS although it improved motor symptoms, motor fluctuations, and the health-related quality of life

Residual excessive daytime sleepiness in patients with sleep apnea syndrome receiving continuous positive airway pressure in Japan: A single-center study

Excessive daytime sleepiness (EDS) is a symptom of sleep apnea syndrome (SAS). In some patients with SAS who undergo continuous positive airway pressure (CPAP) therapy, EDS persists (residual EDS). However, knowledge of residual EDS in Japan is limited. Therefore, we examined EDS as defined by the Japanese version of the Epworth Sleepiness Scale (a score of ≥11) before and after long-term (≥1 year) CPAP therapy in 490 patients with SAS. Good adherence to CPAP therapy was defined as its use for at least 4 h during 70% of the nights. The prevalence of residual EDS was 9.4%. Residual EDS was negatively associated with good adherence to CPAP therapy. Furthermore, the longer the CPAP therapy duration after initiation, the lower the prevalence of residual EDS. Therefore, the findings on the prevalence of residual EDS and its association with CPAP therapy in Japan are probably similar to those of other countries.

0611 Treatment Satisfaction and Preferences in People With Narcolepsy Transitioning From Sodium Oxybate to Lower-Sodium Oxybate

Abstract Introduction Lower-sodium oxybate (LXB; Xywav®), which contains the same active moiety as higher-sodium oxybate (SXB; Xyrem®) but with 92% less sodium, is approved by the US Food and Drug Administration (FDA) for treating cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy. LXB is recognized as clinically superior to SXB in narcolepsy by the US FDA due to lower chronic sodium exposure; however, real-world data describing patient preferences and satisfaction are lacking. Methods Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR; NCT04803786) was a patient-centric, prospective, observational, noninterventional, virtual-format study of US adults with narcolepsy (type 1 or 2) transitioning from SXB to LXB within the previous/upcoming 7 days. Longitudinal data collected during transition and for 21 weeks thereafter included responses to the Ease of Switching Medications Scale (EOSMS), Forced Preference Questionnaire (FPQ), and Treatment Satisfaction Questionnaire for Medication-version II (TSQM-vII). Results The mean (standard deviation [SD]) age of the 85 participants (narcolepsy type 1, n=45; narcolepsy type 2, n=40) was 40.3 (13.0) years; most were female (73%) and White (87%). Mean (SD) time on current SXB regimen was 57.8 (52.1) months. Nearly all participants took SXB (82/85, 96%) twice nightly prior to transition and LXB (82/84, 98%) twice nightly after transition. Most participants (61/73, 84%) reported that switching from SXB to LXB was “extremely easy, not difficult at all” or “easy” on the EOSMS, and most (59/73, 81%) preferred LXB to SXB on the FPQ. Among participants who preferred LXB, lower sodium content (56/59, 95%) and fewer cardiovascular issues (27/59, 46%) were cited as the most common reasons. There were minimal mean (SD) changes in TSQM-vII scores for global satisfaction (1.1 [18.6]), satisfaction with effectiveness (1.0 [16.8]), side effects (4.1 [23.7]), or convenience (−3.9 [15.2]) after transitioning from SXB to LXB. Conclusion Overall, most participants indicated that switching from SXB to LXB was “easy” or “extremely easy.” Most participants preferred LXB to SXB, primarily because of its lower sodium content. Satisfaction with oxybate treatment was maintained following transition to LXB. Support (if any) Jazz Pharmaceuticals

0598 Patient-Reported Sleep Quality in People With Narcolepsy Transitioning From Sodium Oxybate to Lower-Sodium Oxybate

Abstract Introduction Lower-sodium oxybate (LXB; Xywav®), which contains the same active moiety as higher-sodium oxybate (SXB; Xyrem®) but with 92% less sodium, is approved by the US Food and Drug Administration (FDA) for treating cataplexy or excessive daytime sleepiness in patients ≥7 years of age with narcolepsy. LXB is recognized as clinically superior to SXB in narcolepsy by the US FDA due to lower chronic sodium exposure. Real-world data related to sleep quality following transition from SXB to LXB are lacking. Methods Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR; NCT04803786) was a patient-centric, prospective, observational, noninterventional, virtual-format study of US adults with narcolepsy (type 1 or 2) transitioning from SXB to LXB within the previous/upcoming 7 days. Longitudinal data collected during transition and for 21 weeks thereafter were based on daily and weekly questionnaires and sleep diaries instructing participants to rate the quality of their sleep and how refreshed they felt upon waking, and to record their sleep latency, wake after sleep onset (WASO), time in bed (TIB), and total sleep time (TST). Results The mean (standard deviation [SD]) age of the 85 participants (narcolepsy type 1, n=45; narcolepsy type 2, n=40) was 40.3 (13.0) years; most were female (73%) and White (87%). Almost all participants took SXB (82/85, 96%) twice nightly prior to transition and LXB (82/84, 98%) twice nightly after transition. Most participants rated their sleep quality as “good” or “very good” at baseline (45/84, 54%) and end of study (38/71, 54%), while 24/84 (29%) and 30/71 (42%) reported feeling “well-rested” or “very well-rested” at baseline and end of study, respectively. At end of study, changes (n=71) in mean (SD) sleep latency, WASO, TIB, and TST were −10.5 (16.2), −14.8 (56.6), 7.6 (67.7), and 33.0 (93.8) minutes, respectively. Conclusion Although participant-reported sleep quality was generally unchanged during the study, a greater percentage of participants reported feeling refreshed at end of study (on LXB) than at baseline (on SXB); however, there was no non-transitioning arm for comparison. Small changes were noted at end of study in sleep parameters, including sleep latency, WASO, and TST. Support (if any) Jazz Pharmaceuticals

0591 Effectiveness and Optimization of Lower-Sodium Oxybate in Participants With Narcolepsy Switching From Sodium Oxybate (SEGUE)

Abstract Introduction Lower-sodium oxybate (LXB, Xywav®) contains 92% less sodium than higher-sodium oxybate (SXB, Xyrem®) and is approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy (≥7 years of age) and idiopathic hypersomnia in adults. The SEGUE study examines the safety, tolerability, effectiveness, and treatment optimization in participants with narcolepsy transitioning from SXB to LXB. Methods Eligible participants in this multicenter, open-label study were adults with narcolepsy type 1 or 2 who were on a stable dose (maximum 9 g/night; no single dose &amp;gt;6 g) and regimen (once, twice, or thrice nightly) of SXB. After 2 weeks on a stable SXB dose/regimen (baseline period), participants switched to the same dose/regimen of LXB (intervention period; 6 weeks). If needed, LXB dose/regimen was titrated to optimize efficacy/tolerability. Assessments included the Patient Global Impression of Change (PGIc), a forced preference questionnaire (FPQ), an ease of switching medication scale (EOSMS), and the Epworth Sleepiness Scale (ESS); all collected at end of treatment or early discontinuation. Results Of 60 participants who entered the intervention period, a majority were female (62%) and White (88%); mean (SD) age was 43.9 (15.33) years. Starting and ending (end of treatment or early discontinuation) median total nightly doses of LXB were 8.5 g and 9.0 g, respectively. In terms of regimen, most took LXB twice nightly (93% at both time points). Fifty-six participants completed the transition period; mean (SD) time to stable dose was 2.5 (4.82) days, and median (range) number of changes in dose/regimen was 0.0 (0, 1). At end of treatment or early discontinuation, most participants reported improvement (very much/much/minimal; 45%) or no change (48%) in narcolepsy symptoms on the PGIc, preferred LXB over SXB on the FPQ (79%), and reported the transition to LXB was easy, extremely easy, or not difficult at all on the EOSMS (93%). Mean (SD) change from baseline on the ESS (n=55) was −0.7 (2.31). Conclusion Most participants with narcolepsy switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition process was easy. Effectiveness of oxybate treatment (ESS) was maintained after transition, and most preferred LXB over SXB. Support (if any) Jazz Pharmaceuticals.

0609 Samelisant, Histamine 3 Receptor Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy

Abstract Introduction Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant. Methods Samelisant is currently being evaluated in a double blind, Phase-2 proof of concept study in USA and Canada for narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). The study is recruiting subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of &amp;lt; 12 min. A total of 171 subjects are expected to be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio. Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Key secondary endpoint is change in ESS from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by data safety monitoring committee. As the study is still recruiting, demographics and baseline characteristic data for the currently enrolled subjects is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results At the data cutoff date of Nov 30, 2022, a total of 155 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-57 years) with mean BMI of 28.5 kg/m2 (range: 18.3- 43.9 kg/m2). Overall, 57% subjects were of narcolepsy type-1, 71% were female and 71% were Caucasian. Mean (SD) baseline values of MWT and ESS scores were 6.1 (4.4) and 17.2 (2.8), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q2 2023. Support (if any)

Health-related impact of illness associated with excessive daytime sleepiness in patients with obstructive sleep apnea

ABSTRACT Objectives This real-world study aimed to characterize the impact of illness of excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) who are adherent to continuous positive airway pressure (CPAP). Methods This cross-sectional study surveyed participants in Evidation Health’s Achievement app (November 2020–January 2021), a mobile consumer platform that encourages users to develop healthy habits and provides incentives to participate in research. Participants were US-resident adults who self-reported a physician diagnosis of OSA and adherence to CPAP (≥4 hours/night, ≥5 nights/week) for≥6 months. The survey included the Functional Outcomes of Sleep Questionnaire-Short Version (FOSQ-10), Epworth Sleepiness Scale (ESS), and questions regarding comorbidities, CPAP use, caffeine consumption, and physical activity. EDS was defined as ESS score >10. There were more female than male participants; therefore, data were reported separately for females/males. Results In total, 476 participants (female, n = 283 [59%]; mean [SD] age, 49.7 [10.8] years; obese, 74.4%) completed the survey; 209 had EDS (mean [SD] ESS, 13.8 [2.5]) and 267 did not (mean [SD] ESS, 6.3 [2.5]). Self-reported duration of CPAP use was consistent between the EDS/no EDS cohorts, with most participants using CPAP for 7 to 9 hours/night, 7 nights/week. Participants with EDS commonly reported anxiety ([EDS/no EDS] males: 31.5%/20.0%; females: 53.7%/39.5%), depression (males: 35.6%/24.2%; females: 55.9%/44.9%), and insomnia (males: 19.2%/6.7%; females: 25.7%/12.9%) and showed impairment on the FOSQ-10 ([EDS/no EDS] males: 80.8%/35.0%; females: 91.9%/53.1%). Participants with EDS reported that sleepiness ‘very often’ prevented physical activity and influenced dietary choices. Conclusion EDS influences choices related to physical activity, caffeine consumption, and diet in patients who are adherent with CPAP. More research is needed to understand the association between EDS and choices of CPAP-adherent patients. Future research should explore the health-related consequences of residual EDS associated with OSA and whether they can be mitigated by improving EDS.