Sleepiness In Obstructive Sleep Apnea Research Articles

Sleepiness in obstructive sleep apnea using hypopneas defined by a 3% oxygen desaturation or arousal but not by 4% or greateroxygen desaturation.

This analysis determined the association between obstructive sleep apnea (OSA) with hypopneas defined by a 3% O2 desaturation or arousal (3%A), but not by a hypopnea criterion of ≥ 4% (4%), and subjective sleepiness. Data were analyzed from Sleep Heart Health Study participants who had polysomnography (N = 6307) regarding OSA and subjective sleepiness scores (Epworth Sleepiness Scale, ESS). The apnea hypopnea index (AHI) was classified based on 3% only, 3%A only, and 4% definitions of hypopneas. Of the 3326 participants without 4% OSA, 67.6% (n = 2247) had 3%A only OSA. The ESS score was higher in 3%A only OSA than in those without OSA (7.44 ± 4.2 vs 7.07 ± 4.3, P = 0.02). Of those without 4% OSA, 40.2% (n = 1336) had 3% only OSA. The ESS score was higher in those with 3% only OSA than those with no OSA (7.72 ± 4.3 vs 7.05 ± 4.2, P < 0.001). A linear regression model demonstrated a trend towards significance for the 3%A only AHI as an independent predictor of ESS when controlled for age, BMI, and sex (P = 0.051). The association of 3% only AHI with the ESS was stronger (P = 0.003). However, 23.3% of the participants with hypersomnia would not qualify as having OSA if arousals were excluded from the definition of OSA. The current study found that the presence and severity of OSA is associated with higher ESS scores in persons with 3%A only OSA. Hence, the use of the 4% hypopnea definition will result in the failure to identify and treat a significant number of individuals with OSA who have subjective sleepiness.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

Excessive 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. Efficacy 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). A 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. The 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. Ronnebaum S, Bron M, Patel D, etal. 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.

Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy.

This post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment. Participants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups. Common early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity. Common early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment. Registry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606. Rosenberg R, Thorpy MJ, Dauvilliers Y, etal. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.

Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea–hypopnea index ≥ 15/h] and ESS score ≥ 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.

The association between beta-blocker therapy and daytime sleepiness in obstructive sleep apnoea

Daytime sleepiness is a cardinal symptom of obstructive sleep apnoea (OSA) and a well-recognised side effect of beta-blockers, therefore patients with OSA under this treatment may have worse sleepiness. However, the interaction between daytime sleepiness and beta-blockers use has not been thoroughly investigated in patients with OSA before. We analysed the data of 2183 individuals (1852 patients with OSA and 331 snorer controls) from 3 countries (Greece, Hungary and Moldova). Medical history, including medication usage and the Epworth Sleepiness Scale (ESS) were recorded. Patients and controls were divided into somnolent (ESS ≥ 11) and non-somnolent (ESS < 11) groups, and the association between-blocker use with the somnolent group was investigated with multivariate logistic regression analysis adjusted for confounders. Sensitivity analyses were performed in each cohort, in the severity subgroups, in patients who did not take statins and in those who had polysomnography as a diagnostic test. There was no relationship between beta-blocker usage and the somnolent OSA (p = 0.24) or control (p = 0.64) groups. These results were similar in sensitivity analyses (all p > 0.05). ESS was related to BMI (ρ = 0.25), total sleep time (ρ = 0.07), AHI (ρ = 0.32), oxygen desaturation index (ρ = 0.33) and minimum oxygen saturation (ρ = – 0.32, all p < 0.05) in OSA, and was higher in patients with hypertension, diabetes and cerebro/cardiovascular disease and those who took statins (all p < 0.05). In general, beta-blockers are not associated with increased daytime sleepiness in OSA. Thus, the diagnosis of OSA should not discourage initiation of beta-blocker treatment, if it is clinically indicated.

A novel parameter is better than the AHI to assess nocturnal hypoxaemia and excessive daytime sleepiness in obstructive sleep apnoea

To evaluate whether the percentage of total sleep time spent with apnoea and hypopnoea duration time (AHT%) is better than the apnoea-hypopnoea index (AHI) for the assessment of nocturnal hypoxaemia and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnoea (OSA). Patients with suspected OSA were enrolled. Polysomnography, Epworth Sleepiness Scale, self-administered surveys and anthropometric measures were performed. The efficiency of AHT% and the AHI was evaluated for nocturnal hypoxaemia and EDS. A total of 160 eligible participants were analysed. The median AHT% in normal, mild, moderate and severe OSA patients was significantly different in the four-group patients with OSA. Spearman rank correlations analysis found that the associations were stronger between AHT% with percentage of total sleep time and O2 saturation of < 90% and minimum nocturnal oxygen saturation than these parameters with the AHI. AHT% had a greater area under the curve than the AHI for predicting EDS in patients with OSA. AHT% was significantly higher in the EDS group. We present a novel parameter, AHT%, to evaluate nocturnal hypoxaemia and EDS in OSA patients. AHT% partially compensates for the shortcomings of the AHI. AHT% is better than the AHI for assessing nocturnal hypoxaemia and EDS. AHT% reflects different clinical characteristics associated with OSA from a new perspective.

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

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.

Profile of Solriamfetol in the Management of Excessive Daytime Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea: Focus on Patient Selection and Perspectives.

Excessive sleepiness (ES) is a symptom of obstructive sleep apnea (OSA) and narcolepsy that has severe consequences. Wake-promoting drugs and stimulants are utilized as accessory treatment in OSA to reduce propensity to sleep but they do not improve sleep-disordered breathing. Solriamfetol is a first-line therapeutic agent to combat sleepiness in OSA and narcolepsy patients that is approved both by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). For excessively sleepy adult patients with OSA despite primary treatment or narcolepsy patients without cataplexy, solriamfetol may be used as initial therapy or as replacement therapy in patients who fail treatment or experience unacceptable side effects with modafinil, armodafinil, pitolisant, or stimulants. It can also be used as add-on therapy in OSA or narcolepsy patients when ES is only partially controlled with modafinil, armodafinil, pitolisant, sodium oxybate, or stimulants. Solriamfetol is a phenylalanine derivative whose wake-promoting action may be mediated through its selective dopamine and norepinephrine reuptake inhibition. This paper reviews the profile of solriamfetol in treating ES associated with OSA or narcolepsy and discusses patient selection and clinical perspectives. Mechanism of action, pharmacology, pharmacokinetics, clinical efficacy, and tolerability of solriamfetol are described. The Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES) solriamfetol trials demonstrated the efficacy of solriamfetol in reducing propensity to sleep and maintaining wakefulness, with significant improvements in mean maintenance of wakefulness test (MWT) sleep latencies and significant reduction in Epworth Sleepiness Scale (ESS) scores compared to placebo. With solriamfetol, significantly higher percentages of patients showed improvement in patient’s and clinician’s global impression of change.

Inspiratory Muscle Training in the Severity of Obstructive Sleep Apnea, Sleep Quality and Excessive Daytime Sleepiness: A Placebo-Controlled, Randomized Trial.

PurposeExercise programs have been considered as an adjuvant treatment in obstructive sleep apnea (OSA). However, few studies have focused on the effects of the inspiratory muscle training (IMT) in reducing the severity and the symptoms of OSA.Patients and MethodsA randomized controlled trial was conducted and approved by the local Ethics Committee. All subjects signed the informed consent form and were randomized into 2 groups: a) IMT group (n = 8), 8 weeks of IMT with 75% of maximal inspiratory pressure (MIP) and b) placebo group (n = 8): subjects performed IMT without load.ResultsIMT group showed reduction in the apnea–hypopnea index (AHI) (p = 0.01), in the Berlin questionnaire score (p = 0.001) and an increase in inspiratory muscle strength (p = 0.018). IMT group demonstrated a reduction in the AHI (31.7 ± 15.9 events/h vs 29.9 ± 15.8 events/h; p <0.001), in the Berlin questionnaire scores (2.6 ± 0.5 vs 1.2 ± 0.5; p = 0.016), Pittsburgh Sleep Quality Index (PSQI) score (7.2 ± 3.6 vs 3.7 ± 1.3; p = 0.008), in the Epworth Sleepiness Scale (ESS) (12.5 ± 4.0 vs 7.7 ± 3.0; p = 0.008) and increase in MIP (83.6 ± 26.5 cmH2O and 127.9 ± 32.5 cmH2O; p = 0.010).ConclusionThe IMT promotes discrete changes in the AHI and improves sleep quality and excessive daytime sleepiness in OSA. Moreover, IMT is a cheap, useful and simple home-based training program and can be considered as an adjunct therapy for OSA patients.

Randomized clinical trials of cardiovascular disease in obstructive sleep apnea: understanding and overcoming bias.

Three recent randomized control trials (RCTs) found that treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) did not reduce rates of future cardiovascular events. This article discusses the biases in these RCTs that may explain their negative results, and how to overcome these biases in future studies. First, sample selection bias affected each RCT. The subjects recruited were not patients typically presenting for treatment of OSA. In particular, subjects with excessive sleepiness were excluded due to ethical concerns. As recent data indicate that the excessively sleepy OSA subtype has increased cardiovascular risk, subjects most likely to benefit from treatment were excluded. Second, RCTs had low adherence to therapy. Reported adherence is lower than found clinically, suggesting it is in part related to selection bias. Each RCT showed a CPAP benefit consistent with epidemiological studies when restricting to adherent patients, but was underpowered. Future studies need to include sleepy individuals and maximize adherence. Since it is unethical and impractical to randomize very sleepy subjects to no therapy, alternative designs are required. Observational designs using propensity scores, which are accepted by FDA for studies of medical devices, provide an opportunity. The design needs to ensure covariate balance, including measures assessing healthy user and healthy adherer biases, between regular users of CPAP and non-users. Sensitivity analyses can evaluate the robustness of results to unmeasured confounding, thereby improving confidence in conclusions. Thus, these designs can robustly assess the cardiovascular benefit of CPAP in real-world patients, overcoming biases in RCTs.

Chronic toxoplasmosis and sleepiness in obstructive sleep apnea: Is there a link?

IntroductionSleepiness is the main clinical expression of obstructive sleep apnea (OSA) syndrome resulting from upper airway collapse. Recent studies have discussed the fact that the presence of T. gondii cysts in the brain and the resulting biochemical and immunological mechanisms could be linked to neurobehavioral disorders. The aim of the present study was to explore the potential impact of chronic toxoplasmosis on sleepiness and on obstructive sleep apnea (OSA) severity in OSA obese patients.Materials and methodsA case control study on obese patients screened for OSA was performed. According to the sleep disorder and matched based on gender, age and body mass index (BMI), two groups of obese patients were selected from our sample collection database. All patients were tested for toxoplasmosis serological status measuring anti-Toxoplasma IgG and IgM levels. Univariable and multivariable logistic regression models were performed to assess the impact of chronic toxoplasmosis on sleepiness and OSA severity.Results107 obese patients suffering from OSA were included in the study (median age: 53.3 years Interquartile range (IQR): [41.9–59.9]; median BMI: 39.4 kg/m2 IQR: [35.5–44.1], apnea-hypopnea index = 27.5 events/h [10.7–49.9]). Chronic toxoplasmosis was present in 63.4% and 70.7% of patients with or without sleepiness (p = 0.48), respectively and was not associated either to sleepiness (OR: 0.76, 95% CI: [0.52; 2.33], p = 0.64) or OSA severity (OR = 1.75, 95% CI: [0.51; 5.98] p = 0.37).ConclusionAlthough chronic Toxoplasma infection in immunocompetent humans has been associated to several behavioral disorders or pathologies in recent literature, we demonstrate here that chronic toxoplasmosis is not associated to sleepiness and to sleep apnea syndrome severity in obese patients suspected of sleep apnea syndrome.

Incidence and duration of common adverse events in 2 solriamfetol phase 3 studies for treatment of excessive daytime sleepiness in obstructive sleep apnoea and narcolepsy

Incidence and duration of common adverse events in 2 solriamfetol phase 3 studies for treatment of excessive daytime sleepiness in obstructive sleep apnoea and narcolepsy

Different associations of obesity with subjective and objective daytime sleepiness in obstructive sleep apnea

Different associations of obesity with subjective and objective daytime sleepiness in obstructive sleep apnea

Indirect treatment comparison of the efficacy and safety of solriamfetol, modafinil, and armodafinil for the treatment of excessive daytime sleepiness in obstructive sleep apnoea

Indirect treatment comparison of the efficacy and safety of solriamfetol, modafinil, and armodafinil for the treatment of excessive daytime sleepiness in obstructive sleep apnoea

Excessive daytime sleepiness in obstructive sleep apnea: implications for driving licenses.

Excessive daytime sleepiness (EDS) while driving is a major international public health issue resulting in a more than doubled risk of motor vehicle accidents (MVAs). Obstructive sleep apnea (OSA) is the most frequent medical cause of EDS. Therefore, the European Union Directive 2014/85/EU determined that "untreated moderate to severe OSA coincident with EDS constitutes a medical disorder leading to unfitness to drive." The paper aims are to provide a brief review of sleepiness and its implications for driving safety, as well as to describe the subjective and objective methods to accurately evaluate EDS in order to assess fitness to drive in patients with OSA. We examined databases including PubMed, Medline, and EMBASE using the search terms "sleepiness at the wheel, excessive daytime sleepiness, sleepiness measure, sleep-wake cycle, obstructive sleep apnea, driving license, fitness to drive." Significant interindividual variability in EDS exists in patients with comparable severity of OSA. Objective methods of measuring EDS are too expensive and time consuming to be suitable for the certification of driving licenses. The reliability of subjective methods depends upon the clinical setting and subjective tools assess only limited aspects of EDS. Objective measures, such as biochemical biomarkers, must, therefore, support subjective methods. Extensive data have supported different subjective and objective methods for the appraisal of EDS in patients with OSA depending upon the clinical and experimental setting. Challenges remain to determine an appropriate tool for the evaluation of fitness to drive.

Microsleep as a marker of sleepiness in obstructive sleep apnea patients.

We hypothesized that: (a) the presence of microsleep (MS) during a Maintenance Wakefulness Test (MWT) trial may represent a reliable marker of sleepiness in obstructive sleep apnea (OSA) patients; (b) the number of MSs will be higher in sleepy versus non-sleepy patients with a borderline MWT mean sleep latency; and (c) scoring MS during MWT analysis may help physicians to recognize patients with a higher degree of sleepiness. We analysed the MWT data of 112 treatment-naïve OSA patients: 20 with short sleep latency (SL, sleep latency <12.8min), 43 with borderline latency (BL, sleep latency between 12.8 and 32.6min) and 49 with normal latency (NL, sleep latency >32.6min). Microsleep was identified in all SL, in 42 BL and in 18 NL patients, with a median latency of 5.6min. Accordingly, patients were classified into two subgroups: group A (n=43) with microsleep latency <5.6min and group B (n=69) with microsleep latency >5.6min when present. The mean sleep latency in the MWT was 14.5±7.5min in group A and 34.6±7.4min in group B (p<0.0001). The number of microsleep episodes during each MWT trial was higher in group A than in group B. Sleep latency survival curves demonstrated different patterns of sleep latency in these groups (log-rank test <0.0001). This finding was confirmed in a Cox proportional hazard analysis: the presence of a mean MS latency <5.6min is associated with an increasing risk of falling asleep during the MWT (RR, 1.93; 95 CI 1.04-3.6; p=0.03). We conclude that the detection of microsleep may help in discriminating OSA patients with and without daytime vigilance impairment.

Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial.

Rationale: Primary treatment of obstructive sleep apnea can be accompanied by a persistence of excessive sleepiness despite adherence. Furthermore, effectiveness of sleep apnea treatment is limited by poor adherence. Currently available pharmacologic options for the treatment of sleepiness in this population are limited. Objectives: To evaluate the efficacy and safety of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, for the treatment of excessive sleepiness in participants with obstructive sleep apnea with current or prior sleep apnea treatment. Methods: This was a double-blind, randomized, placebo-controlled, parallel-group, 12-week trial comparing solriamfetol, 37.5, 75, 150, and 300 mg, with placebo. Measurements and Main Results: Of 476 randomized participants, 459 were included in the prespecified efficacy analyses. Coprimary endpoints (Maintenance of Wakefulness Test sleep latency and Epworth Sleepiness Scale score) were met at all solriamfetol doses (P < 0.05), with dose-dependent effects observed at Week 1 maintained over the study duration. All doses except 37.5 mg resulted in higher percentages of participants reporting improvement on Patient Global Impression of Change (key secondary endpoint; P < 0.05). Adverse events were reported in 47.9% of placebo- and 67.9% of solriamfetol-treated participants; five participants experienced serious adverse events (two [1.7%] placebo, three [0.8%] solriamfetol); none were deemed related to study drug. The most common adverse events with solriamfetol were headache (10.1%), nausea (7.9%), decreased appetite (7.6%), anxiety (7.0%), and nasopharyngitis (5.1%). Conclusions: Solriamfetol significantly increased wakefulness and reduced sleepiness in participants with obstructive sleep apnea and excessive sleepiness; most adverse events were mild or moderate in severity. Clinical trial registered with www.clinicaltrials.gov (NCT02348606) and www.eudract.ema.europa.eu (EudraCT 2014-005514-31).

0569 Incidence and Duration of Common Adverse Events in a Solriamfetol (JZP-110) Phase 3 Study for Treatment of Excessive Daytime Sleepiness in Obstructive Sleep Apnea

0569 Incidence and Duration of Common Adverse Events in a Solriamfetol (JZP-110) Phase 3 Study for Treatment of Excessive Daytime Sleepiness in Obstructive Sleep Apnea

Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea

ABSTRACTIntroduction: Obstructive sleep apnea (OSA) is highly prevalent and constitutes a major health hazard. Current pharmacotherapy is ineffective in correcting sleep-disordered breathing and is used adjunctively to address residual sleepiness. A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients.Areas covered: This review covers drug chemistry, pharmacodynamics, pharmacokinetics, and metabolism of solriamfetol. Results of three Phase 3 trials, Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES 3, 4, 5), relevant to OSA patients are summarized. Published abstracts/articles and a 2017 Jazz Investor Presentation provided data. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.Expert commentary: Solriamfetol shows promise as adjunctive therapy in OSA. It is well tolerated and effective in reducing sleepiness and is an alternative to modafinil or armodafinil. Unlike stimulants like methylphenidate or dextroamphetamine, it does not have cardiac effects, rebound hypersomnia, or withdrawal effects.

0585 Understanding Excessive Daytime Sleepiness In Obstructive Sleep Apnea: The Effect Of Online Medical Education On Neurologists And Pulmonologists

0585 Understanding Excessive Daytime Sleepiness In Obstructive Sleep Apnea: The Effect Of Online Medical Education On Neurologists And Pulmonologists