sodium-oxybate and Sleep-Wake-Disorders

Sleep and wake are two fundamental states of human existence. Conditions such as insomnia and hypersomnia can have profound negative effects on human health. Many pharmacological interventions impacting sleep and wake are available or are under development. This brief digest surveys early approaches to sleep modulation and highlights recent developments in sleep modulating agents.

Topics: Animals; Humans; Sleep; Sleep Aids, Pharmaceutical; Sleep Wake Disorders; Wakefulness-Promoting Agents

Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of narcolepsy have been described (narcolepsy type 1 and narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with narcolepsy type 1. The pathogenesis of narcolepsy type 1 is hypothesized to be the autoimmune destruction of the hypocretin-producing neurons in the hypothalamus; this hypothesis is supported by immune-related genetic and environmental factors associated with the disease. However, direct evidence in support of the autoimmune hypothesis is currently unavailable. Diagnosis of narcolepsy encompasses clinical, electrophysiological and biological evaluations, but simpler and faster procedures are needed. Several medications are available for the symptomatic treatment of narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions.

Topics: Adjuvants, Anesthesia; Benzhydryl Compounds; Biomarkers; Cataplexy; Genetic Predisposition to Disease; HLA-DQ beta-Chains; Humans; Modafinil; Narcolepsy; Orexins; Quality of Life; Risk Factors; Serotonin and Noradrenaline Reuptake Inhibitors; Sleep Wake Disorders; Sodium Oxybate; Wakefulness-Promoting Agents

Studies examining GABA(B) receptor agonists have reported effects on sleep including decreased sleep onset latency (SOL), increased sleep consolidation and increases in slow wave sleep (SWS). γ-hydroxybutyrate (GHB) is proposed to act as a GABA(B) receptor agonist; however, the mechanism of action of GHB is controversial. In addition, the GABA(B) receptor agonist, baclofen, has also been proposed to exert similar effects on sleep. The aim of this paper is to provide a review of the human clinical studies of sodium oxybate and baclofen regarding sleep and the treatment of sleep disorders including narcolepsy and insomnia, as well as other disorders involving disrupted sleep such as fibromyalgia.

Topics: Animals; Baclofen; GABA-B Receptor Agonists; Humans; Narcolepsy; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Sodium Oxybate

Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that is synthesized within the CNS, mostly from its parent compound gamma amino butyric acid (GABA). GHB acts as a neuromodulator/neurotransmitter to affect neuronal activity of other neurotransmitters and so, stimulate the release of growth hormone. Its sodium salt (sodium oxybate: SXB) was approved by the Food and Drug Administration (FDA) for the treatment of narcolepsy. SXB has shown to improve disrupted sleep and increase NR3 (slow-wave restorative) sleep in patients with narcolepsy. It is rapidly absorbed and has a plasma half-life of 30 - 60 min, necessitating twice-nightly dosing. Most of the observed effects of SXB result from binding to GABA-B receptors.. Several randomized, controlled trials demonstrated significantly improved fibromyalgia (FM) symptoms with SXB. As seen in narcolepsy trials, SXB improved sleep of FM patients, increased slow-wave sleep duration as well as delta power, and reduced frequent night-time awakenings. Furthermore, FM pain and fatigue was consistently reduced with nightly SXB over time. Commonly reported adverse events included headache, nausea, dizziness and somnolence. Despite its proven efficacy, SXB did not receive FDA approval for the management of FM in 2010, mostly because of concerns about abuse.. Insomnia, fatigue and pain are important clinical FM symptoms that showed moderate improvements with SXB in several large, well-designed clinical trials. Because of the limited efficacy of currently available FM drugs additional treatment options are needed. In particular, drugs like SXB - which belong to a different drug class than other Food and Drug Administration (FDA)-approved FM medications such as pregabalin, duloxetine and milnacipran - would provide a much-needed addition to presently available treatment options. However, the FDA has set the bar high for future SXB re-submissions, with requirements of superior efficacy and improved risk mitigation strategies. At this time, no future FDA submission of SXB for the fibromyalgia indication is planned.

Topics: Adjuvants, Anesthesia; Animals; Drug Approval; Fibromyalgia; Humans; Pain; Protein Binding; Receptors, GABA-B; Sleep Wake Disorders; Sodium Oxybate; United States; United States Food and Drug Administration

Gamma-hydroxybutyrate (GHB) is a short fatty acid and physiologic neurotransmitter. Initially, it was synthesized as a GABA agonist and used as a narcotic agent, because it rapidly induces sleep without major cardiovascular or respiratory side effects. Recently, a specific GHB receptor was identified, but while the clinical use of GHB as an anaesthetic was reduced due to putative pro-convulsive effects, it now is used to treat alcohol withdrawal and sleep disorders. Furthermore, GHB was postulated to be a regulator of energy metabolism, and tissue-protective effects were demonstrated in different animal models. Besides its clinical use, GHB (also called "liquid ecstasy") is increasingly consumed in the disco scene because of its mild sedative and euphoric effects. Intoxication from GHB is common with GHB users. For this reason and because GHB is not easy to detect, it is important to be aware of the symptoms of GHB intoxication. Moreover, some recent case reports document the danger of GHB dependence.

Topics: Alcohol Withdrawal Delirium; Anesthetics, Intravenous; Brain; Humans; Neurotransmitter Agents; Sleep Wake Disorders; Sodium Oxybate; Substance-Related Disorders; Treatment Outcome

Narcolepsy is a severely debilitating neurologic disease that is not as rare as many believe, affecting an estimated 140,000 Americans. Despite the sometimes debilitating nature of narcolepsy symptoms, the disease may go undiagnosed without an organized method for evaluating patients with sleep complaints. Many of the classic symptoms of narcolepsy, such as excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations, may be mistakenly associated with other disease states and must be differentiated from other sleep disorders. The results of self-administered sleep-disorder questionnaires are useful and may increase the suspicion of narcolepsy; however, referral to an accredited sleep laboratory for a formal sleep study including overnight polysomnography is necessary for a positive narcolepsy diagnosis. A variety of medications may be used to successfully treat excessive daytime sleepiness and cataplexy, the two most debilitating symptoms of the disease. Primary-care physicians who develop the proper diagnostic skills can play a pivotal role in the accurate diagnosis and long-term management of patients suffering from narcolepsy.

Topics: Adjuvants, Anesthesia; Algorithms; Diagnosis, Differential; Humans; Narcolepsy; Sleep Wake Disorders; Sodium Oxybate; Voluntary Health Agencies

Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce.. To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD.. Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale [ESS] score >10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12).. Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed.. Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale-2), and objective variables of nighttime sleep (polysomnography).. Among 12 patients in the intention-to-treat population (10 men, 2 women; mean [SD] age, 62 [11.1] years; disease duration, 8.4 [4.6] years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, -4.2 points ; 95% CI, -5.3 to -3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P < .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment.. This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation.. clinicaltrials.gov Identifier: NCT02111122.

Topics: Adjuvants, Anesthesia; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Polysomnography; Sleep Wake Disorders; Sodium Oxybate; Treatment Outcome

Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms.. 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing.. Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p≤0.001) and 25% for SXB6 g/night (p≤0.001) versus 0.5% for placebo. Adverse events with an incidence ≥5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema.. These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affords important benefits across multiple symptoms in subjects with fibromyalgia.

Topics: Adjuvants, Anesthesia; Adult; Female; Fibromyalgia; Follow-Up Studies; Health Status; Humans; Male; Middle Aged; Musculoskeletal Pain; Patient Satisfaction; Quality of Life; Sleep; Sleep Wake Disorders; Sodium Oxybate

This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an endogenous compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a ≥30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) (P<0.001 for both comparisons). Relative to placebo, both SXB doses significantly reduced fatigue (with a 100-mm VAS; P<0.001) and sleep disturbance (with the Jenkins Sleep Scale; P<0.001), and resulted in significant improvements in function as measured by the FM Impact Questionnaire (P=0.003 and P=0.001 for 4.5 and 6 g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of "much" or "very much" better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.

Topics: Adjuvants, Anesthesia; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Pain Measurement; Quality of Life; Sleep Wake Disorders; Sodium Oxybate; Treatment Outcome

Cluster headache (CH) manifests with periodic attacks of severe unilateral pain and autonomic symptoms. Nocturnal attacks may cause severe sleep disruption. In about 10%of cases, patients present with a chronic form (CCH), which is often medically intractable. Few attempts have been made to improve headache via pharmacologic modulation of sleep.. In an open-label study, 4 patients with CCH and disturbed sleep received increasing dosages of sodium oxybate (SO), a compound known to consolidate sleep and to increase slow-wave sleep. Response to SO was monitored by serial polysomnography, and actimetry, along with pain and sleep diaries.. SO was effective in all 4 patients as shown by an immediate reduction in frequency (up to 90%) and intensity (>50%) of nocturnal pain attacks and improved sleep quality. These effects were long-lasting in 3 patients (mean 19 months, range 12-29 months) and transient (for 8 months) in one patient. Long-lasting improvement of daytime headaches was achieved with a latency of weeks in 2 patients. SO was safe, with mild to moderate adverse effects (dizziness, vomiting, amnesia, weight loss).. SO may represent a new treatment option to reduce nocturnal and diurnal pain attacks and improve sleep quality in CCH. These data also suggest the interest of treating primary headache syndromes by sleep-manipulating substances.. This study provides Class IV evidence that oral SO at night improves sleep and reduces the intensity and frequency of headaches in patients with CCH.

Topics: Adjuvants, Anesthesia; Adult; Chronic Disease; Cluster Headache; Female; Humans; Longitudinal Studies; Male; Middle Aged; Pain Measurement; Polysomnography; Sleep Wake Disorders; Sodium Oxybate; Young Adult

To determine the effects of sodium oxybate (SXB) on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome (FM).. Of 304 patients with FM (American College of Rheumatology tender point criteria) in the screened study population, 209 underwent polysomnography, 195 were randomized, and 151 completed this 8-week, double-blind, placebo-controlled study of SXB 4.5 g and 6 g/night. We evaluated changes in objective sleep measures and subjective symptoms, including daytime sleepiness [Epworth Sleepiness Scale (ESS)], fatigue visual analog scale (FVAS), sleep [Jenkins Scale for Sleep (JSS)], and daytime functioning [Functional Outcome of Sleep Questionnaire (FOSQ), SF-36 Vitality domain, and Fibromyalgia Impact Questionnaire (FIQ) general and morning tiredness].. Pretreatment screening revealed an elevated incidence of maximum alpha EEG-intrusion > 24 min/hour of sleep (66%), periodic limb movements of sleep (20.1% ≥ 5/hour), and moderate to severe obstructive sleep apnea disorder (15.3% apnea-hypopnea index ≥ 15/hour). Compared with placebo, both doses of SXB achieved statistically significant improvements in ESS, morning FVAS, JSS, FOSQ, SF-36 Vitality, and FIQ general and morning tiredness; both doses also demonstrated decreased rapid eye movement (REM) sleep (all p ≤ 0.040). SXB 6 g/night improved afternoon, evening and overall FVAS, reduced wakefulness after sleep onset, and increased Stage 2, slow-wave, and total non-REM sleep (all p ≤ 0.032) versus placebo. Moderate correlations (≥ 0.40) were noted between changes in subjective sleep and pain measures. Adverse events occurring significantly more frequently with SXB than placebo were nausea, pain in extremity, nervous system disorders, dizziness, restlessness, and renal/urinary disorders (including urinary incontinence).. This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms.

Topics: Adjuvants, Anesthesia; Adult; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Placebos; Polysomnography; Sleep; Sleep Wake Disorders; Sodium Oxybate; Surveys and Questionnaires; Treatment Outcome

Previous studies indicate that nightly sodium oxybate administration reduces nocturnal sleep disruption in narcolepsy. The present study provided an opportunity to further characterize these sleep-related effects in patients with narcolepsy during treatment with sodium oxybate as monotherapy or in combination with modafinil.. This double-blind, placebo-controlled study enrolled 278 patients with narcolepsy taking modafinil 200-600 mg daily for the treatment of excessive daytime sleepiness (EDS). Following a baseline polysomnogram (PSG) and Maintenance of Wakefulness Test (MWT), patients were randomized to receive treatment with: (1) placebo, (2) sodium oxybate, (3) modafinil, or (4) sodium oxybate+modafinil. PSGs and MWTs were repeated after 4 and 8 weeks. Other efficacy measures included Epworth Sleepiness Scale scores and daily diary recordings.. After 8 weeks, significant changes in sleep architecture among patients receiving sodium oxybate and sodium oxybate/modafinil included a median increase in Stage 3 and 4 sleep (43.5 and 24.25 min, respectively) and delta power and a median decrease in nocturnal awakenings (6.0 and 9.5, respectively). No significant changes in PSG parameters were noted in patients treated with placebo or modafinil alone.. In addition to its established efficacy for the treatment of cataplexy and EDS, nightly sodium oxybate administration significantly reduces measures of sleep disruption and significantly increases slow-wave sleep in patients with narcolepsy.

Topics: Adjuvants, Anesthesia; Adult; Benzhydryl Compounds; Central Nervous System Stimulants; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Modafinil; Narcolepsy; Placebos; Polysomnography; Sleep; Sleep Wake Disorders; Sodium Oxybate; Wakefulness

Many patients with Parkinson disease (PD) have excessive daytime sleepiness and numerous nocturnal sleep abnormalities.. To determine the safety and efficacy of the controlled drug sodium oxybate in a multicenter, open-label, polysomnographic study in subjects with PD and sleep disorders. Design, Setting, and Patients Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleep-disordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off ("off") PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started sodium oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an off-medication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD).. We enrolled 38 subjects. At screening, 8 had sleep apnea (n = 7) or depression (n = 1). Twenty-seven of 30 subjects completed the study. Three dropped out owing to dizziness (n = 3) and concurrent depression (n = 1). The mean dose of sodium oxybate was 7.8 (1.7) g per night. The ESS score improved from 15.6 (4.2) to 9.0 (5.0) (P < .001); the Pittsburgh Sleep Quality Inventory score, from 10.9 (4.0) to 6.6 (3.9) (P < .001); and the Fatigue Severity Scale score, from 42.9 (13.2) to 36.3 (14.3) (P < .001). Mean slow-wave sleep time increased from 41.3 (33.2) to 78.0 (61.2) minutes (P = .005). Changes in off-medication UPDRS scores were not significant, from 28.4 (10.3) to 26.2 (9.6).. Nocturnally administered sodium oxybate improved excessive daytime sleepiness and fatigue in PD.. clinicaltrials.gov Identifier: NCT00641186.

Topics: Adjuvants, Anesthesia; Adult; Aged; Antiparkinson Agents; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Parkinson Disease; Polysomnography; Sleep Apnea Syndromes; Sleep Initiation and Maintenance Disorders; Sleep Stages; Sleep Wake Disorders; Sodium Oxybate; Treatment Outcome

Fibromyalgia (FM) is associated with the sleep phenomenon of alpha intrusion, and with low growth hormone secretion. Sodium oxybate has been shown to increase both slow-wave sleep and growth hormone levels. This double blind, randomized, placebo controlled crossover trial was conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain, fatigue, and sleep quality and the objective polysomnographic (PSG) sleep variables of alpha intrusion, slow-wave (stage 3/4) sleep, and sleep efficiency in patients with FM.. Patients received either 6.0 g/day sodium oxybate or placebo for 1 month, with an intervening 2 week washout period. Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements from daily diary entries. Safety measures included clinical laboratory values, vital signs, and adverse events.. Twenty-four female patients were included in the study; 18 completed the trial. TPI was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p = 0.0079). Six of the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003).. Sodium oxybate effectively reduced the symptoms of pain and fatigue in patients with FM, and dramatically reduced the sleep abnormalities (alpha intrusion and decreased slow-wave sleep) associated with the nonrestorative sleep characteristic of this disorder.

Topics: Adjuvants, Anesthesia; Adult; Aged; Alpha Rhythm; Cross-Over Studies; Female; Fibromyalgia; Humans; Middle Aged; Sleep Wake Disorders; Sleep, REM; Sodium Oxybate; Treatment Outcome

To evaluate the effects of using a gamma-hydroxybutyrate (GHB) administered in divided doses at night in 11 patients previously diagnosed with fibromyalgia (FM).. Subjects completed daily diaries assessing their pain and fatigue levels and slept in the sleep laboratory before and one month after initiating GHB treatment. Polysomnographic recordings were evaluated for sleep stages, sleep efficiency and the presence of the alpha anomaly in non-REM sleep.. There was a significant improvement in both fatigue and pain, with an increase in slow wave sleep and a decrease in the severity of the alpha anomaly.. Further controlled studies are needed to characterize the clinical improvement and the polysomnographic changes we observed.

Topics: Adult; Fatigue; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Pilot Projects; Polysomnography; Sleep Wake Disorders; Sodium Oxybate

Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid β, suggesting a mechanism for sleep disturbances to increase Alzheimer disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with

Topics: Adult; Alzheimer Disease; Amyloid beta-Peptides; Anesthetics; Circadian Rhythm; Female; Humans; Kinetics; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Peptide Fragments; Pilot Projects; Sleep; Sleep Wake Disorders; Sodium Oxybate

Topics: Adjuvants, Anesthesia; Chronic Disease; Cluster Headache; Humans; Sleep Wake Disorders; Sodium Oxybate

Hypnosedative-induced complex behaviors have gained increased attention in recent years as a potential complication of benzodiazepines and benzodiazepine-receptor agonist use. Sodium oxybate (SO), the sodium salt of γ-hydroxybutyrate, an inhibitory neurotransmitter, has been associated with dose-dependent rates of somnambulism; however, there is limited information about complex motor behaviors with SO. We describe a patient with narcolepsy-cataplexy who experienced one episode of sleep-driving and at least two sleep-related eating episodes with therapeutic doses of SO.

Topics: Adjuvants, Anesthesia; Adult; Automobile Driving; Feeding and Eating Disorders; Humans; Male; Narcolepsy; Parasomnias; Sleep Wake Disorders; Sodium Oxybate

Topics: Cause of Death; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Product Surveillance, Postmarketing; Retrospective Studies; Sensitivity and Specificity; Sleep Wake Disorders; Sodium Oxybate; Survival Analysis; United States

Topics: Benzhydryl Compounds; Drug Interactions; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Mental Disorders; Modafinil; Sleep Wake Disorders; Sodium Oxybate

Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology.. We overview the phenotype of 33 adolescents and adults (10.1-39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data.. Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14% from 2-4 years of age, mean age at first symptoms was 11+/-12 months. However, mean age at diagnosis was 6.6+/-6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had >or=3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized.. The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.

Topics: Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Ataxia; Behavioral Symptoms; Child; Child, Preschool; Cohort Studies; Developmental Disabilities; Electroencephalography; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Intellectual Disability; Language Development Disorders; Male; Seizures; Sleep Wake Disorders; Sodium Oxybate; Succinate-Semialdehyde Dehydrogenase; Surveys and Questionnaires

Patients with sleep disorders present with a variety of complaints including excessive daytime sleepiness, daytime spells, inability to sleep, uncomfortable sensation in the extremities, and unusual night time behaviors. This article provides eight vignettes on patients with sleep disorders including narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement behavior disorder. The discussion provides data regarding the epidemiology, pathophysiology, and diagnostic approach for these conditions. The various treatment options for these sleep disorders are also identified.

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Aged; Aged, 80 and over; Cataplexy; Disorders of Excessive Somnolence; Electroencephalography; Female; HLA Antigens; Humans; Male; Middle Aged; Narcolepsy; Polysomnography; REM Sleep Behavior Disorder; Restless Legs Syndrome; Sleep Apnea, Obstructive; Sleep Stages; Sleep Wake Disorders; Sodium Oxybate

Seven patients suffering from restless legs syndrome (RLS) and periodic movements in sleep (PMS) were investigated before and after treatment with L-Dopa. The effect of treatment was evaluated by polysomnography, structured interviews, and daily questionnaires. Sleep organization and subjective complaints improved during treatment with 100 to 200 mg of L-Dopa. Polysomnographic recordings also revealed a significant decrease of periodic leg movements during the first third of the night and a rebound during the last third. These results and previous biochemical findings raise the hypothesis that RLS and PMS may both result from reduced dopaminergic activity in the CNS, perhaps resulting from decreased sensibility of postsynaptic receptors.

Topics: Adult; Central Nervous System; Dopamine; Female; Humans; Levodopa; Male; Movement Disorders; Restless Legs Syndrome; Sleep Wake Disorders; Sodium Oxybate; Synaptic Transmission

The effects of sodium hydroxybutyrate (100 mg/kg); phenazepam (1 mg/kg), apomorphine (0.1 mg/kg and haloperidol (1 mg/kg) on the electrophysiological sleep pattern were studied in rats during 7-day alcohol withdrawal after its voluntary consumption for 13 months. It was shown that alcohol withdrawal led to profound disorders in the sleep-waking cycle. Sodium hydroxybutyrate prevented these disturbances and brought sleep to normal. Phenazepam exerted a powerful sedative and hypnotic effects but did not improve the balance of sleep phases. Apomorphine displayed a tendency to sleep normalization. However, this effect was short-term. Haloperidol did not eliminate abstinence manifestations in the sleep pattern.

Topics: Alcoholism; Animals; Anti-Anxiety Agents; Apomorphine; Benzodiazepines; Benzodiazepinones; Haloperidol; Humans; Male; Psychotropic Drugs; Rats; Sleep Wake Disorders; Sodium Oxybate; Substance Withdrawal Syndrome

Five non-narcoleptic hypersomniac patients were given GHB (3.10 to 4.5 g per os) at night. Four patients reported a persistent improvement of their daytime sleepiness as a result of this treatment. Nocturnal polygraphic recordings were performed in all patients before and after GHB. The durations of sleep and of waking times were reduced after GHB while there was an increase of stages 3 and 4 during the first third of the night. It is possible that the increase in delta wave sleep early in the night is responsible for a re-establishment of a normal distribution of subsequent sleep stages and thus produces a more recuperative sleep.

Topics: Adult; Disorders of Excessive Somnolence; Female; Humans; Hydroxybutyrates; Male; Sleep; Sleep Wake Disorders; Sleep, REM; Sodium Oxybate; Time Factors