A randomized study of solriamfetol for excessive sleepiness in narcolepsy

Objective: Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy. Methods: Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Results: Safety and modified intention-to-treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and −6.4 (SE = 0.7) for 300 mg and −5.4 (SE = 0.7) for 150 mg on the ESS versus −1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI-C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%). Interpretation: Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359–370

Changes in Cataplexy Frequency in a Clinical Trial of Lower-Sodium Oxybate with Taper and Discontinuation of Other Anticataplectic Medications

Correction:Background Lower-sodium oxybate (LXB) is an oxybate medication with the same active moiety as sodium oxybate (SXB) and a unique composition of cations, resulting in 92% less sodium. LXB was shown to improve cataplexy and excessive daytime sleepiness in people with narcolepsy in a placebo-controlled, double-blind, randomized withdrawal study (NCT03030599). Additional analyses of data from this study were conducted to explore the effects of LXB on cataplexy, including the clinical course and feasibility of transition from other anticataplectics to LXB monotherapy. Objective The aim of these analyses was to evaluate cataplexy frequency during initiation/optimization of LXB and taper/discontinuation of prior antidepressant/anticataplectic medications. Methods Eligible participants (adults aged 18-70 years with narcolepsy with cataplexy) entered the study taking SXB only (group A), SXB + other anticataplectics (group B), or anticataplectic medication other than SXB (group C), or were cataplexy-treatment naive (group D). LXB was initiated/optimized during a 12-week, open-label, optimized treatment and titration period (OLOTTP). Other anticataplectics were tapered/discontinued during weeks 3-10 of OLOTTP. A 2-week stable-dose period (SDP; during which participants took a stable dose of open-label LXB) and 2-week double-blind randomized withdrawal period (during which participants were randomized to continue LXB treatment or switch to placebo) followed OLOTTP. Treatment-emergent adverse events (TEAEs) were recorded throughout the duration of the study. Results At the beginning of OLOTTP, median weekly cataplexy attacks were lower in participants taking SXB at study entry (SXB only [2.00]; SXB + other anticataplectics [0.58]) versus participants who were taking other anticataplectics (3.50) or were anticataplectic naive (5.83). Median weekly cataplexy attacks decreased during weeks 1-2 of OLOTTP in all groups. Increased cataplexy frequency was observed in participants tapering/discontinuing other anticataplectics during weeks 3-10 and was more prominent in participants taking other anticataplectics alone compared with those taking SXB plus other anticataplectics. Cataplexy frequency decreased throughout initiation/optimization in anticataplectic-naive participants. Median number of cataplexy-free days/week at the end of SDP (study week 14) was similar in all groups (6.0, 6.1, 6.0, and 6.2 in groups A, B, C, and D, respectively). During OLOTTP and SDP, TEAEs of worsening cataplexy were reported in 0%, 47.8%, 16.7%, and 2.2% of participants in groups A, B, C, and D, respectively; most TEAEs of worsening cataplexy were reported during tapering/discontinuation of other anticataplectics. Conclusions LXB monotherapy was effective in reducing cataplexy and increasing cataplexy-free days. These results illustrate the feasibility of switching from SXB to LXB while tapering/discontinuing other anticataplectics.Peer reviewe

Sleep-disordered breathing and cognitive functioning in preschool children with and without Down syndrome

BACKGROUND: Sleep affects children's cognitive development, preparedness for school and future academic outcomes. People with Down syndrome (DS) are particularly at risk for sleep‐disordered breathing (SDB). To our knowledge, the association between SDB and cognition in preschoolers with DS is unknown. METHODS: We assessed sleep by using cardiorespiratory polygraphy in 22 typically developing (TD) preschoolers and 22 with DS. Cognition was assessed by using the Mullen Scales of Early Learning and behaviour by using the Strengths and Difficulties Questionnaire (SDQ). The MacArthur Communicative Development Inventory (MCDI) measured language level. We predicted that sleep problems would be associated with lower cognitive and behavioural functioning. RESULTS: In TD children, longer sleep duration was associated with higher scores on MCDI expressive language and fewer emotional symptoms such as fear and unhappiness on the SDQ, whilst SDB was associated with increased conduct problems and less prosocial behaviour on the SDQ. Conversely, for children with DS, SDB was associated with increased language understanding and use of actions and gestures on the MCDI. CONCLUSIONS: The findings in the TD group support our hypotheses. We recommend that sleep problems are screened for and treated as even mild SDB may prompt poorer cognition and behaviour. For children with DS, we expect that multiple factors in this complex syndrome mask or mediate the association between sleep and cognitive development and tighter controls are necessary to uncover effects of sleep. We propose longitudinal studies as a necessary tool to assess the precise impact of sleep on cognitive development in accounting for individual differences in DS

Narcolepsy, driving and traffic safety

Driving performance in narcolepsy patients is often affected. This is predominantly caused by excessive daytime sleepiness and disturbed vigilance. To a lesser extent cataplexy and sleep paralysis may play a role as well. This chapter discusses experimental studies assessing driving performance in both treated and untreated patients with narcolepsy. Driving simulator studies, on-road tests in actual traffic, and psychological test batteries show that untreated narcolepsy may significantly impair driving ability and increase the risk of becoming involved in traffic accidents. However, much more research is needed to evaluate the effects of narcolepsy treatment on driving in normal traffic, and epidemiological data on traffic accident risks should be gathered. Relatively few studies have been performed to examine effects of narcolepsy treatment on driving ability. Up to now driving improvement has been demonstrated in patients who are successfully treated with methamphetamine and modafinil. Future driving studies should examine the effect of other treatment options

Use of near-infrared light to reduce symptoms associated with restless legs syndrome in a woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a potential new treatment option for patients suffering from restless legs syndrome. Contemporary treatment for restless legs syndrome consists mostly of dopaminergic drugs that leave some patients feeling nauseated and dizzy. A non-invasive, drug-free option would open new doors for patients suffering from restless legs syndrome.</p> <p>Case presentation</p> <p>A 69-year-old Caucasian woman met International Restless Legs Syndrome Study Group criteria for the diagnosis of restless legs syndrome. She had been afflicted with restless legs syndrome for over 30 years and tried many of the available pharmaceutical remedies without success. For this study she received 30-minute treatment sessions with near-infrared light, three times a week for four weeks. The restless legs syndrome rating scale was used to track symptom changes; at baseline she scored "27" on the 0 to 40 point scale, which is considered to be "severe". Our patient was almost symptom free at week two, indicated by a score of "2" on the rating scale. By week four she was completely symptom free. The symptoms slowly returned during week three post treatment.</p> <p>Conclusions</p> <p>The findings suggest that near-infrared light may be a feasible method for treating patients suffering from restless legs syndrome. Undesirable side-effects from medication are non-existent. This study might revive the neglected vascular mechanism theory behind restless legs syndrome and encourage further research into this area.</p

P003 Randomised, placebo-controlled study of solriamfetol for excessive daytime sleepiness in narcolepsy types 1/2

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Sleep disturbances in an arctic population: The Tromsø Study

<p>Abstract</p> <p>Background</p> <p>Prevalence estimates for insomnia range from 10 to 50% in the adult general population. Sleep disturbances cause great impairment in quality of life, which might even rival or exceed the impairment in other chronic medical disorders. The economic implications and use of health-care services related to chronic insomnia represent a clinical concern as well as a pronounced public health problem. Hypnotics are frequently prescribed for insomnia, but alcohol and over-the-counter sleep aids seem to be more widely used by insomniacs than prescription medications. Despite the complex relationship between insomnia and physical and mental health factors, the condition appears to be underrecognized and undertreated by health care providers, probably due to the generally limited knowledge of the causes and natural development of insomnia.</p> <p>Methods/Design</p> <p>The Tromsø Study is an ongoing population-based cohort study with five previous health studies undertaken between 1974 and 2001. This protocol outlines a planned study within the sixth Tromsø Study (Tromsø VI), aiming at; 1) describing sleep patterns in a community-based sample representative of the general population of northern Norway, and 2) examining outcome variables of sleep disturbances against possible explanatory and confounding variables, both within a cross-sectional approach, as well as retrospectively in a longitudinal study – exploring sleep patterns in subjects who have attended two or more of the previous Tromsø studies between 1974 and 2009. First, we plan to perform a simple screening in order to identify those participants with probable sleep disturbances, and secondly to investigate these sleep disturbances further, using an extensive sleep-questionnaire. We will also collect biological explanatory variables, i.e. blood samples, weight, height and blood pressure. We plan to merge data on an individual level from the Tromsø VI Study with data from the Norwegian Prescription Database (NorPD), which is a national registry including data for all prescription drugs issued at Norwegian pharmacies. Participants with sleep disturbances will be compared with pair-matched controls without sleep disturbances.</p> <p>Discussion</p> <p>Despite ongoing research, many challenges remain in the characterization of sleep disturbances and its correlates. Future mapping of the biological dimensions, natural history, as well as the behavioral and drug-related aspects of sleep disturbances in a representative population samples is clearly needed.</p