sodium-oxybate and Sleep-Initiation-and-Maintenance-Disorders

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

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and nocturnal sleep disruption. Non-pharmacological treatments (i.e., behavioral modification) are often helpful for the clinical management of narcoleptic patients. As these symptoms are often disabling, most patients need life-long treatments. Over 90% of diagnosed narcoleptic patients are currently prescribed medications to control their symptoms; however, available treatments are merely symptomatic.. This review presents a description of the clinical symptoms of narcolepsy, followed by a discussion of the state-of-the-art knowledge regarding the disorder and related emerging treatments. In preparing this review, an extensive literature search was conducted using Pubmed. Only selected references from 1970 to 2008 are cited.. This review focuses on emerging treatments for human narcolepsy, and the reader will gain significant knowledge of current and future treatment for this and related disorders. Traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS, and tricyclic antidepressants have been used as anticataplectics. However, treatments have recently evolved which utilize better tolerated compounds, such as modafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night time administration of a short-acting sedative, gamma-hydroxybutyrate, has been used for the treatment for EDS and cataplexy. As a large majority of human narcolepsy is hypocretin peptide deficient, hypocretin replacement therapy may also be a new therapeutic option; yet, this option is still unavailable. In addition to the hypocretin-based therapy, a series of new treatments are currently being tested in animal and/or humans models. These potential options include novel stimulant and anticataplectic drugs as well as immunotherapy, based on current knowledge of the pathophysiology of narcolepsy with cataplexy.. We expect that more pathophysiology-based treatments, capable of curing and/or preventing narcolepsy and related diseases, will be available in near future. As cases of EDS, associated with other neurological conditions (i.e., symptomatic narcolepsy or narcolepsy due to medical conditions), are often linked with hypocretin deficiency, these novel therapeutic options may also be applied to treatment of these disabling conditions.

Topics: Animals; Antidepressive Agents; Cataplexy; Cell Transplantation; Central Nervous System Stimulants; Drugs, Investigational; Genetic Therapy; Hallucinations; Humans; Immunologic Factors; Intracellular Signaling Peptides and Proteins; Narcolepsy; Neuropeptides; Orexins; Sleep Initiation and Maintenance Disorders; Sleep Paralysis; Sodium Oxybate; Wakefulness

Topics: Adjuvants, Anesthesia; Female; Humans; Male; Polysomnography; Psychiatric Status Rating Scales; Schizophrenia; Sleep Initiation and Maintenance Disorders; Sodium Oxybate

To evaluate the safety and efficacy of sodium oxybate for management of the symptoms of fibromyalgia syndrome (FMS).. Patients with FMS (according to the American College of Rheumatology 1990 criteria) were randomized, after discontinuing their prestudy medications for FMS, to receive 4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks. The primary outcome variable (POV) was a composite score for changes from baseline in 3 coprimary self-report measures: patient's pain rating (in daily electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI-C). A beneficial response rate for the POV composite score was defined as >or=20% improvement in the PVAS and FIQ scores plus a rating of "much better" or "very much better" on the PGI-C. Secondary measures included subjective sleep outcomes (on the Jenkins Scale for Sleep) and quality-of-life measures. The analyses were based on an intent-to-treat (ITT) population.. The ITT population included 188 patients with FMS, 78% of whom completed the trial. Significant benefit was observed with both dosages of sodium oxybate, according to changes in the POV and subjective sleep quality. Improvements in the PVAS score were significantly correlated with sleep outcomes. Sodium oxybate was well tolerated overall; dose-related nausea (

Topics: Adjuvants, Anesthesia; Adult; Anxiety; Double-Blind Method; Female; Fibromyalgia; Humans; Male; Middle Aged; Pain; Patient Compliance; Placebos; Quality of Life; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Treatment Outcome

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

Our case describes clinical features of two families defined by joint phenotypes: sodium oxybate intolerance and elevated serum acylcarnitines. Oxybate intolerance variably presents as either cervical dystonia or sleep-related eating disorder. Our objective is to identify biological markers which predict a poor response to sodium oxybate as a treatment for disturbed sleep. Familial inheritance pattern, genotype analysis, multiorgan system involvement, and response to treatment suggest the presence of a secondary cause of fatty oxidation defect, i.e., mitochondrial disorder. Our case report supports the possible conclusion that variance in human mitochondrial metabolism may affect sodium oxybate tolerability.

Topics: Acyl-CoA Dehydrogenase; Carnitine; Child; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Narcolepsy; Polymorphism, Single Nucleotide; Sleep Initiation and Maintenance Disorders; Sodium Oxybate

Chronic pain and sleep disorder can put the patient in a vicious circle (bidirectional relation between those two morbid entities). Clinical management must be global. The physiopathology includes chronic sleep deficit, mainly in deep sleep (the "restoring" sleep) generated principally by the prefrontal regions. These areas are also implicated in the modulation of pain. To break this "loops", we advocate an approach based on three main components: hygiene principles, cognitive and behavioral therapy, medications with analgesic and hypnotic proprieties.

Topics: Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Anticonvulsants; Behavior Therapy; Brain; Chronic Disease; Cognitive Behavioral Therapy; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Hypnotics and Sedatives; Life Style; Melatonin; Pain; Pain Management; Placebos; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Treatment Outcome

Topics: Adjuvants, Anesthesia; Adult; Cognitive Behavioral Therapy; Humans; Male; Paroxetine; Phobic Disorders; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors; Sleep Initiation and Maintenance Disorders; Sodium Oxybate

Topics: Adult; Conscious Sedation; Emergency Treatment; Hallucinations; HIV Seropositivity; Humans; Male; Respiration, Artificial; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Substance Withdrawal Syndrome; Tremor

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.

Topics: Adult; Anesthetics, Intravenous; Anxiety; Coma; Female; Humans; Male; Sleep Initiation and Maintenance Disorders; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Tremor