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Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management.

ABSTRACT: Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.

SUBMITTER: Lal C

PROVIDER: S-EPMC8086534 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study objectivesExcessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea.MethodsEfficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation).ResultsA systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events.ConclusionsThe results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea.CitationRonnebaum S, Bron M, Patel D, et al. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Project description:Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

Project description:BACKGROUND:Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient's health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. METHODS:Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. RESULTS:Over three-fifths of study participants (n?=?26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n?=?14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n?=?1, 2%) or were treatment naïve (n?=?1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ?1?year, with an average duration of 11.4 (median 8.0, range 1-37) years before seeking medical attention. Several (n?=?7, 32%) considered their symptoms to be "normal," rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n?=?20, 67%); their own concern about particular symptoms (n?=?7, 23%); and/or falling asleep while driving (n?=?5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n?=?40, 95%); work productivity (n?=?38, 90%); daily life functioning (n?=?39, 93%); cognition (n?=?38, 90%); social life/relationships (n?=?37, 88%); and emotions (n?=?30, 71%). CONCLUSIONS:Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

Project description:Excessive daytime sleepiness (EDS) is a hallmark symptom in obstructive sleep apnea (OSA). It is commonly eliminated by obstructive sleep apnea therapy and constitutes a major treatment indication. This study aimed to identify determinants of excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS) scores in the large, representative national obstructive sleep apnea patient cohort of the Swedish Sleep Apnea Registry (SESAR, www.sesar.se). Data from 34,684 patients with obstructive sleep apnea recruited at 23 sites (33% females, mean age 55.7 ± 13.7 years, BMI 30.2 ± 6.3 kg/m2 , AHI 29.1 ± 22.3, and ODI 24.9 ± 21.4 events/h) had a mean ESS score in the mild to moderate excessive daytime sleepiness range (9.7 ± 4.9). The proportion of patients with excessive daytime sleepiness was 41.4% in men and 44.6% in women. Independent predictors of excessive daytime sleepiness included gender, age, and hypoxic markers (high ODI and low mean saturation). Univariate and multivariate analyses were used to identify significant predictors for the ESS score and for excessive daytime sleepiness (ESS ≥10) amongst anthropometric factors, sleep apnea frequency (apnea-hypopnea index (AHI)), markers of intermittent hypoxia (oxygen desaturation index (ODI), mean saturation (mSaO2 )), as well as prevalent comorbidities. Depression was associated with higher ESS scores and hypertension/atrial fibrillation with lower scores. The oxygen desaturation index provided a stronger predictor of excessive daytime sleepiness than the apnea-hypopnea index. The severity of obstructive sleep apnea, captured as the apnea-hypopnea index, was only weakly associated with daytime sleepiness in this representative obstructive sleep apnea patient cohort. Age had different effects in men and women.The impact of obstructive sleep apnea in a wider patient related perspective needs to be determined after the inclusion of factors other than the apnea-hypopnea index.

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Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management.

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