Introduction Solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, demonstrated robust wake-promoting effects in 12-week studies of excessive daytime sleepiness (EDS) associated ...with obstructive sleep apnea (OSA) or narcolepsy. Efficacy and safety of solriamfetol were evaluated from pooled analyses of these studies. Methods Data from 12-week studies (2 narcolepsy, 1 OSA) were evaluated. Efficacy assessments included change from baseline to week 12 on mean sleep latency on Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score, and patient-reported improvement on Patient Global Impression of Change (PGI-C) scale. Safety was also assessed. Results Compared with participants with OSA (n=113 placebo, 343 solriamfetol combined doses), those with narcolepsy (n=105 placebo, 215 solriamfetol) were younger, with more females, and lower body mass index. Baseline MWT mean sleep latency and ESS scores were more severe for narcolepsy compared with OSA. Change from baseline to week 12 in MWT mean sleep latency increased in a dose-related manner compared with placebo, with least square (LS) mean differences of 2.2, 7.4, and 10.4 for 75, 150, and 300mg, respectively, for narcolepsy, and 4.7, 9.0, 11.1, and 13.0 for 37.5, 75, 150, and 300mg, respectively, for OSA. Dose-related effects were also observed for change from baseline to week 12 in ESS score, with LS mean differences of -1.8, -3.8, and -5.2 for 75, 150, and 300mg, respectively, for narcolepsy, and -2.0, -1.9, -4.5, and -4.8 for 37.5, 75, 150, and 300mg, respectively, for OSA. At week 12, the percentage of participants reported as improved on PGI-C was increased relative to placebo; results were similar between disorders. In the overall population, the most frequent (≥5%) adverse events were headache, nausea, decreased appetite, anxiety, nasopharyngitis, diarrhea, and dry mouth; the incidence was comparable in OSA and narcolepsy. Conclusion Solriamfetol showed consistent efficacy and safety findings in both narcolepsy and OSA subjects. Solriamfetol increased wakefulness and reduced sleepiness in both groups and the adverse events profile was similar for both groups. Support (If Any) Jazz Pharmaceuticals
Introduction Excessive daytime sleepiness (EDS) is a debilitating non-motor symptom affecting patients with Parkinson’s Disease (PD). Solriamfetol has demonstrated wake-promoting efficacy in clinical ...trials in narcolepsy and obstructive sleep apnea (OSA). Methods This was a phase 2, double-blind, placebo-controlled, randomized, 4-week, crossover trial. Eligible participants were 35-80 years of age, diagnosed with mild to moderate idiopathic PD (UK PDS Brain Bank Criteria), with Epworth Sleepiness Scale (ESS) score >11. Participants were randomized (3:3:1) to receive one week of: A) placebo, solriamfetol 75mg, 150mg, and 300mg, B) solriamfetol 75mg, 150mg, 300mg, and placebo, or C) four weeks of placebo. Safety and tolerability were primary objectives and included assessment of adverse events. Efficacy endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT) and ESS score. Results Participants (n=66) were randomized (mean SD age, 64.6 8.5; 68.2% male) and n=62 completed the trial. At baseline, mean (SD) ESS score was 16.1 (2.9), and MWT sleep latency was 15.1 min (10.9). The most common treatment-emergent adverse events (≥5%) reported while taking solriamfetol were nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), and dyspepsia (5.4%). Least Square (LS) mean (SE) change from baseline in MWT (min) was 1.8 (1.9) for placebo, 0.4 (2.1) for 75mg (nominal p>0.05), 2.7 (2.2) for 150mg (nominal p>0.05), and 6.8 (2.1) for 300mg (nominal p=0.0098). LS mean (SE) change from baseline in ESS was -4.8 (0.6) for placebo, -4.8 (0.7) for 75mg, -5.0 (0.7) for 150mg and -5.7 (0.7) for 300mg; for change in ESS, all nominal p>0.05. Conclusion The safety and tolerability of solriamfetol in PD was demonstrated; participants were able to safely titrate to 300mg, and adverse events were similar to narcolepsy and OSA trials. Solriamfetol treatment improved sleep latency on the MWT at 300mg but not at lower doses. While ESS improvement with solriamfetol was not different from placebo, the large placebo response, likely multifactorial in basis, may have confounded interpretation. Support (If Any) Jazz Pharmaceuticals
Introduction Solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, reduced excessive daytime sleepiness (EDS) and increased wakefulness in participants with obstructive sleep ...apnea (OSA) in a phase 3 study. Post-hoc analysis evaluated timing and duration of common, early-onset, treatment-emergent adverse events (TEAEs). Methods Patients (N=474) with OSA and EDS were randomized to 12 weeks placebo or solriamfetol 37.5, 75, 150, or 300 mg. Common, early-onset TEAEs were defined as those occurring in ≥5% of participants in any solriamfetol dose group and greater than placebo during week 1. For TEAEs identified during week 1, incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Analysis included placebo (n=119) and combined solriamfetol groups (n=355). Results Common early-onset TEAEs during week 1 across all solriamfetol doses were decreased appetite (5.6%), headache (5.1%), anxiety (3.9%), nausea (3.7%), feeling jittery (3.7%), and insomnia (3.1%). Incidence was highest at week 1 and decreased over time; at week 12, only headache, nausea, and anxiety TEAEs were reported (all 0.3%). Fourteen of 25 TEAE-related discontinuations on solriamfetol were due to a common early-onset TEAE (1, decreased appetite 0.3%; 1, headache 0.3%; 4, anxiety 1.1%; 3, nausea 0.8%; 4, feeling jittery 1.1%; 1, insomnia 0.3%). Median durations (days; min, max) for common TEAEs were decreased appetite, 57 (5, 91); headache, 5.5 (1, 112); anxiety, 26 (1, 94); nausea, 10 (1, 86); feeling jittery, 4 (1, 49); insomnia, 8.5 (1, 49). Conclusion In a phase 3 clinical trial of solriamfetol for the treatment of EDS in participants with OSA, common early-onset TEAEs were decreased appetite, headache, anxiety, nausea, feeling jittery, and insomnia. Most early-onset TEAEs had a median duration ≤10 days; and while all diminished over time, they accounted for ~50% of TEAE-related discontinuations across the study. This analysis may inform clinician and patient expectations regarding type, course, and duration of common early-onset TEAEs associated with solriamfetol therapy. Support (If Any) Jazz Pharmaceuticals.
Various aspects of human performance were assessed in children after sleep loss.
Sixteen children (7 males, 9 females) between the ages of 10 and 14 years.
Children were randomly assigned to either a ...control (CTRL) group, with 11 hours in bed, or an experimental sleep restriction (SR) group, with 5 hours in bed, on a single night in the sleep laboratory.
Both groups were evaluated the following day with a battery of performance and sleepiness measures. Psychomotor and cognitive performance tests were given during four 1-hour testing sessions at 2-hour intervals.
A multiple sleep latency test (MSLT) documented shorter latencies for SR children than controls. Significant treatment differences were discovered in three of four variables of verbal creativity, including fluency, flexibility, and average indices. There were also group differences found on the Wisconsin Card Sorting Test (WCST), which may be indicative of difficulty learning new abstract concepts. Measures of rote performance and less-complex cognitive functions, including measures of memory and learning and figural creativity, did not show differences between groups, perhaps because motivation could overcome sleepiness-related impairment for these tasks.
Higher cognitive functions in children, such as verbal creativity and abstract thinking, are impaired after a single night of restricted sleep, even when routine performance is relatively maintained.
To assess patterns of pharmacological treatment of insomnia during the period 1987-1996.
Data were obtained from the National Disease and Therapeutic Index (NDTI; IMS America, Ltd., Plymouth Meeting, ...PA) which samples office-based physicians in 24 specialties. Drug mentions, a measure of patient contacts in which drug therapy is recommended, with a physician-indicated desired action of "promote sleep" or "sedative night" were compiled for each year. Z-scores were calculated to determine statistical differences over time for total drug mentions, drug mentions by category (hypnotics, non-hypnotic benzodiazepines, antidepressants, or other), and for some individual drugs.
Total drug mentions for the treatment of insomnia fell 24.4% from 1987 to 1996. From 1987 to 1996 hypnotic mentions decreased 53.7%, antidepressants increased 146%, "other" drugs decreased by 63.2%, and benzodiazepine non-hypnotics remained relatively unchanged.
Since 1987, overall pharmacological treatment of insomnia has decreased substantially although surveys indicate a stable or increasing prevalence of sleep disturbance. There has also been a dramatic shift to use of antidepressants in lieu of hyponotics for the symptomatic treatment of insomnia despite a paucity of data regarding their efficacy and the potential for serious side effects.
Obstructive sleep apnea (OSA) is characterized by decreased breathing events that occur through the night, with severity reported as the apnea-hypopnea index (AHI), which is associated with certain ...craniofacial features. In this study, we used data from 1366 patients collected as part of Stanford Technology Analytics and Genomics in Sleep (STAGES) across 11 US and Canadian sleep clinics and analyzed 3D craniofacial scans with the goal of predicting AHI, as measured using gold standard nocturnal polysomnography (PSG). First, the algorithm detects pre-specified landmarks on mesh objects and aligns scans in 3D space. Subsequently, 2D images and depth maps are generated by rendering and rotating scans by 45-degree increments. Resulting images were stacked as channels and used as input to multi-view convolutional neural networks, which were trained and validated in a supervised manner to predict AHI values derived from PSGs. The proposed model achieved a mean absolute error of 11.38 events/hour, a Pearson correlation coefficient of 0.4, and accuracy for predicting OSA of 67% using 10-fold cross-validation. The model improved further by adding patient demographics and variables from questionnaires. We also show that the model performed at the level of three sleep medicine specialists, who used clinical experience to predict AHI based on 3D scan displays. Finally, we created topographic displays of the most important facial features used by the model to predict AHI, showing importance of the neck and chin area. The proposed algorithm has potential to serve as an inexpensive and efficient screening tool for individuals with suspected OSA.
SUMMARY Hypnotic medication reliably improves sleep during the day, in terms of increasing total sleep time (TST) and reducing awakenings and light sleep. Middle‐aged individuals may benefit more ...than young adults. In addition, the time of day during which sleep is attempted may influence the efficacious dose of short‐acting drugs. Available data suggest that improving sleep during the day may improve alertness/performance at night to a mild degree, but significant circadian‐related sleepiness remains. Hypnotic medication may help minimize the cumulative effects of sleep loss associated with daytime sleep. Use for more than one week has not been adequately studied; however, as most night and rotating workers' schedules allow for night‐time sleep for two or more nights per week, available evidence indicates that hypnotics can be used effectively on an intermittent basis, e.g. for the first 2–4 day‐sleep periods of night shifts. Caffeine has been shown to increase alertness and improve psychomotor performance during usual night‐shift hours when taken between 22.30 and 01.20 hours. Available data indicate that at approximate dosages of 250–400 mg, the beneficial effects persist until at least 05.30 hours. For most subjects, caffeine taken at the start of the night‐shift does not interfere significantly with daytime sleep beginning at 09.00 hours. There is also some evidence that single doses of caffeine at the beginning of a night shift may be more alerting than divided doses. If caffeine is to be used therapeutically, avoidance of social use may be required to avoid tolerance to CNS stimulant effects. Despite the positive results of laboratory research examining hypnotics or caffeine as shiftwork countermeasures, field trials have not been conducted.
Marked sleepiness occurs during typical night shift work hours and this reduced alertness is associated with marked performance deficits. The effect of caffeine (versus placebo) upon sleepiness at ...night was studied using objective measures of physiological sleep tendency and ability to sustain wakefulness. Both measures show caffeine to reduce sleepiness at a single dose roughly the equivalent of two to four cups of coffee. Despite impressive objective differences in alertness with caffeine, subjects did not consistently differentiate between drug conditions on subjective alertness assessments. The use of CNS stimulants to promote alertness during night shift hours should be considered, particularly for occupations for which alertness is critical.
This autoethnographic essay represents the authors' critical reflection on their experiences partnering with Liz Lerman and Dance Exchange (a dance company) artists on a collaborative evaluation of ..."The Matter of Origins", a contemporary art and science dance performance. They describe meaningful moments in their collaboration and reexamine those pivotal experiences in the broader context of scholarly community engagement. Based on their reflections, the authors identified themes including ethnographic approaches to collaboration, shared systems of meaning, and developmental evaluation to understand the complex experiences that took place at the engagement interface. The essay concludes with suggested reflective questions for scholars to consider in their own community engagement activities. (Contains 1 endnote.)
Objective: To examine the hypnotic efficacy of zaleplon 10 mg, a selective benzodiazepine receptor agonist, over a period of 35 nights in primary insomniacs.
Methods: A double-blind, parallel-group, ...placebo-controlled design was employed. Subjects were 113 men and women, ages 18 to 65 years. Polysomnographic and subjective sleep data were collected during baseline, on two nights during each of five treatment weeks, and on the first two nights after discontinuation of active medication.
Results: Sleep latency was significantly shortened with zaleplon 10 mg for all 5 weeks of treatment as assessed by polysomnography and by subjective sleep measures. Total sleep time, whether evaluated with polysomnography or with subjective estimates, was inconsistently affected. Sleep architecture was similar with zaleplon and placebo. There was no evidence of tolerance to the sleep promoting effects of zaleplon during the five weeks of administration, and there was no rebound insomnia upon discontinuation. Adverse events occurred with equal frequency in the zaleplon and placebo groups.
Conclusions: Zaleplon 10 mg is effective in the treatment of sleep onset insomnia over a period of 35 nights, with minimal evidence of undesired effects.
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