sodium-oxybate and Hallucinations

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

Narcolepsy is a serious neurological condition in which patients are overcome by persistent, excessive feelings of fatigue and drowsiness. In addition to chronic fatigue, patients with narcolepsy often succumb to intermittent, uncontrollable periods where they abruptly fall asleep during waking hours. In addition to episodic bouts of daytime sleeping, narcoleptics also exhibit cataplexy, sleep paralysis, and hypnagogic and hypnopompic hallucinations. Unfortunately, many individuals with narcolepsy remain undiagnosed and therefore, untreated, posing a risk to themselves and those around them. There is currently no cure for this lifelong disease. Nonetheless, narcolepsy can be effectively managed with medications, lifestyle changes, and the peripheral support of individuals such as family members, coworkers, and other casual relations.

Topics: Benzhydryl Compounds; Biomarkers; Cataplexy; Central Nervous System Stimulants; Decision Making; Diagnosis, Differential; Drug Approval; Hallucinations; Humans; Intracellular Signaling Peptides and Proteins; Life Style; Methylphenidate; Modafinil; Narcolepsy; Neuropeptides; Orexins; Physicians, Family; Polysomnography; Primary Health Care; Quality of Life; Respiration; Risk Factors; Sleep Paralysis; Sleep Stages; Sodium Oxybate; United States; United States Food and Drug Administration

Narcolepsy is a disabling disease with a prevalence of 0.05%. It is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnogogic hallucinations, automatic behavior, and disrupted nocturnal sleep. The presentation can be very variable, making diagnosis difficult. Loss of hypocretin containing neurons in the lateral hypothalamus has been noted in autopsy studies, and the cerebrospinal fluid level of hypocretin is reduced in patients with narcolepsy with cataplexy. New treatment options are available for the many symptoms of this disease. Early recognition and treatment can greatly improve the quality of life of patients with narcolepsy. A detail review of the epidemiology, pathophysiology, and management of narcolepsy in children is presented.

Topics: Benzhydryl Compounds; Cataplexy; Central Nervous System Stimulants; Child; Dextroamphetamine; Ghrelin; Hallucinations; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Methylphenidate; Modafinil; Narcolepsy; Neuropeptides; Orexins; Polysomnography; Randomized Controlled Trials as Topic; Sleep, REM; Sodium Oxybate

Narcolepsy is an incurable sleep disorder characterized by attacks of sleepiness and a series of auxiliary symptoms: cataplexy, sleep paralysis and hypnagogic hallucinations. Classic treatment has included stimulants to control sleepiness and tricyclic antidepressants to control the auxiliary symptoms. Polysomnography is necessary to confirm the diagnosis and to detect other sleep disorders. Recent developments in treatment include the use of codeine for sleepiness and gamma-hydroxybutyrate for auxiliary symptoms.

Topics: Amphetamines; Cataplexy; Hallucinations; Humans; Narcolepsy; Paralysis; Propranolol; Sleep Stages; Sodium Oxybate

Thirty patients with polysomnographically confirmed narcolepsy were treated with GHB (gamma-hydroxybutyrate) for up to 30 weeks. The number of nightly awakenings significantly decreased, while Stages 3 and 4 sleep substantially increased. The clinical symptoms of cataplexy, sleep paralysis, hypnogogic hallucinations, daily naps, and sleep attacks all showed significant improvements. Daytime sleepiness, while not completely eliminated, was controlled with lower doses of stimulant medication than patients were taking before the study. No patient developed tolerance to the drug, and no serious side effects were noted.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Cataplexy; Clinical Trials as Topic; Dextroamphetamine; Drug Therapy, Combination; Female; Hallucinations; Humans; Hydroxybutyrates; Male; Methamphetamine; Methylphenidate; Middle Aged; Narcolepsy; Pemoline; Sleep; Sodium Oxybate; Wakefulness

To report a challenging patient a girl who developed narcolepsyy with cataplexy (NT1) and a psychosis during adolescence. To discuss diagnostic and therapeutic challenges of the comorbid cases.. A 14-year-old girl was referred to Sleep and Epilepsy Unit for excessive daytime sleepiness, impaired nocturnal sleep, binge eating and weight gain, over the last year. After being diagnosed with a NT1 the patient was treated with modafinil and sodium oxybate. She was hospitalized for psychotic symptoms after starting NT1 treatment. Withdrawal of the narcolepsy treatment and initiation of haloperidol 1 mg/day (the only antipsychotic treatment she could tolerate) improved the delusions, hallucinations and dysphoria but worsened the narcolepsy symptoms. Polysomnography showed fragmented nocturnal sleep and five sleep REM onset periods in MSLT. Positive HLA-QB1*06:02 and undetectable level of hypocretine in the cerebrospinal fluid were found. MRI and CT-scan were normal. Diagnostic Interview for Genetic Studies Adapted for Narcolepsy (DIGSAN) questionnaire confirmed that patient presented a dual diagnostic NT1 and psychotic symptoms. The last sleep follow-up while on psychopharmacological treatment, showed an increased sleep efficiency index. She currently has severe somnolence, obesity, and partial cataplectic attacks along with normal mood, academic failure and social isolation.. The coexistence of narcolepsy with psychoses is a rare clinical entity, more frequent in adolescents than in adults. The comorbidity of the two illnesses worsens clinical and therapeutic prognosis and also suggests interesting pathophysiological hypotheses.. Narcolepsia-cataplejia y psicosis: estudio de un caso.. Objetivo. Describir una paciente que en la adolescencia desarrollo narcolepsia con cataplejia (NT1) y psicosis. Caso clinico. Niña de 14 años remitida a la unidad de sueño por presentar somnolencia diurna, sueño nocturno fragmentado, hambre compulsiva y aumento de peso durante el ultimo año. Tratada inicialmente con modafinilo y oxibato sodico, tuvo que ser hospitalizada por presentar sintomas psicoticos. Se suprimio el tratamiento antinarcoleptico y se administraron antipsicoticos. El unico que tolero fue el haloperidol 1 mg/dia, con mejoria del delirio, las alucinaciones y los sintomas disforicos, pero con empeoramiento de los sintomas narcolepticos. La polisomnografia mostro un sueño nocturno muy fragmentado, y en la prueba de latencias multiples del sueño, la latencia de sueño fue de un minuto, y tuvo cinco adormecimientos directos en la fase del sueño REM. Presentaba HLA-DQB1*06:02 positivo y nivel de hipocretina-1 en el liquido cefalorraquideo indetectable. La entrevista diagnostica para estudios geneticos adaptada para narcolepsia (DIGSAN) ayudo a confirmar que presentaba una doble patologia de NT1 y sintomas psicoticos. La ultima revision de su sueño con tratamiento psicofarmacologico muestra un aumento del indice de eficacia del sueño. Clinicamente presenta somnolencia diurna excesiva, ataques parciales de cataplejia y una obesidad muy importante. No muestra alteraciones del humor, pero tiene fracaso escolar y aislamiento social. Conclusion. La coexistencia de narcolepsia con psicosis es una entidad clinica rara, mas frecuente en adolescentes que en adultos. La comorbilidad de ambas enfermedades tiene un mal pronostico clinico y terapeutico, y sugiere hipotesis fisiopatologicas interesantes.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Female; Food Addiction; Hallucinations; Haloperidol; HLA-DQ beta-Chains; Humans; Learning Disabilities; Methylphenidate; Modafinil; Narcolepsy; Orexins; Pediatric Obesity; Polysomnography; Psychotic Disorders; Risperidone; Sleep Deprivation; Sleep Latency; Social Isolation; Sodium Oxybate; Suicidal Ideation

The usual age at onset of narcolepsy with cataplexy is in the second or third decade. In cases with late onset narcolepsy with cataplexy, symptoms are usually mild with relatively less severe daytime sleepiness and less frequent cataplexy. Here we present a case of narcolepsy with cataplexy with onset of symptoms around sixty years of age. This case is unique, with severe daytime sleepiness both by subjective report as well as on objective Multiple Sleep Latency Test and having multiple cataplexy episodes in a day.

Topics: Amphetamine; Cataplexy; Central Nervous System Stimulants; Dextroamphetamine; Diagnosis, Differential; Hallucinations; Humans; Male; Middle Aged; Narcolepsy; Polysomnography; Sodium Oxybate

Much of what is understood regarding gamma hydroxybutyrate (GHB) treatment is based on hospital case studies for overdose and withdrawal, and there are currently no measures developed specifically for GHB or its analogs (e.g., gamma butyrolactone and 1,4-butanediol) to assess drug effect expectancies, reasons for starting use, withdrawal effects, and knowledge and opinions about use.. This pilot study (N = 61) was conducted to begin measures development to assess experiences, functions of use, and opinions regarding use as indicated by respondents taking a Web-based survey.. Minimum average partial correlation and parallel analysis procedures are employed to create scales.. Scales were developed to assess expectancies, reasons for use, withdrawal, and knowledge/opinions of use with median α = .79 and that account for 8.69-24.17% of the variance.. Scales have relatively good psychometric properties and replication is needed.. GHB-specific measures may greatly assist in furthering our understanding of protective and risk factors for use, and withdrawal phenomena.

Topics: Adult; Anxiety; Delirium; Drug Users; Female; Hallucinations; Humans; Illicit Drugs; Male; Pilot Projects; Psychiatric Status Rating Scales; Sodium Oxybate; Substance Withdrawal Syndrome; Surveys and Questionnaires

A 35-year-old man had been using high doses of gamma-hydroxybutyrate (GHB) for many years. He had been trying to cut down on use of this drug for 2 months. He was admitted to the hospital suffering from a withdrawal delirium accompanied by hallucinations and agitation. Use of GHB is increasing in the Netherlands. Along with serious intoxication and dependency, the possibility of withdrawal symptoms should also be taken into consideration. Administration of high doses of benzodiazepines is an effective treatment for these withdrawal symptoms.

Topics: Adult; Benzodiazepines; Delirium; Hallucinations; Humans; Male; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adult; Cataplexy; Comorbidity; Cyclohexanols; Hallucinations; Humans; Male; Morpholines; Narcolepsy; Patient Education as Topic; Reboxetine; Selective Serotonin Reuptake Inhibitors; Sodium Oxybate; Venlafaxine Hydrochloride

We report two adult patients with succinic semialdehyde dehydrogenase deficiency, manifesting as gamma-hydroxybutyric aciduria. For both, the clinical presentation included significant behavioral disturbances and psychosis (hallucinations, disabling anxiety, aggressive behavior, and sleep disorder), leading to multiple therapeutic attempts. Intervention with benzodiazepines appeared most efficacious, resulting in decreased aggression and agitation and improvement in anxiety. A review of 56 published and unpublished studies of SSADH-deficient patients revealed that 42% manifested behavioral disturbances, whereas 13% (predominantly adults) displayed psychotic symptomatology. To explore the potential biochemical basis of these behavioral abnormalities, we studied cerebrospinal fluid derived from 13 patients, which revealed significantly elevated GHB (65- to 230-fold), high free and total GABA (up to threefold), and low glutamine. Although within the control range, homovanillic and 5-hydroxyindoleacetic acids (end products of dopamine and serotonin metabolism, respectively) showed a significant linear correlation with increasing GHB concentration, suggesting enhanced dopamine and serotonin turnover. We conclude that elevated GABA combined with low glutamine suggest disruption of the glial-neuronal glutamine/GABA/glutamate shuttle necessary for replenishment of neuronal neurotransmitters, whereas altered dopamine and serotonin metabolism may be causally linked to the hyperkinetic movement disorders and behavioral disturbances seen in SSADH-deficient patients.

Topics: Adult; Aldehyde Oxidoreductases; Atrophy; Cerebellum; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Female; gamma-Aminobutyric Acid; Globus Pallidus; Glutamic Acid; Hallucinations; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Intellectual Disability; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors; Sodium Oxybate; Statistics as Topic; Succinate-Semialdehyde Dehydrogenase

A 27-year-old man was admitted with tremulousness, diaphoresis, tachypnea (28 breaths/min), full-body rigidity, irritability, paranoia, and auditory and visual hallucinations 2 days after stopping long-term gamma-hydroxybutyrate (GHB) and 8 hours after stopping alcohol intake. He received intravenous fluids and tapering dosages of lorazepam to control agitation and rigidity, and recovered with no significant sequelae after 8 days. Abrupt cessation of GHB after high-dosage abuse can precipitate a clinically significant withdrawal syndrome. Lorazepam should be considered for treatment of GHB withdrawal. Concomitant alcohol abuse may mask early GHB withdrawal symptoms and exacerbate withdrawal.

Topics: Adult; Anesthetics, Intravenous; Anticonvulsants; Central Nervous System Depressants; Ethanol; Fluid Therapy; Hallucinations; Humans; Lorazepam; Male; Muscle Rigidity; Sodium Oxybate; Substance Withdrawal Syndrome

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

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient's symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated.

Topics: Adult; Akathisia, Drug-Induced; Anti-Anxiety Agents; Autonomic Nervous System Diseases; Emergencies; GABA Modulators; Hallucinations; Humans; Hypertension; Lorazepam; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Tachycardia; Tremor

We describe what we believe is the first psychiatric hospitalization due to GHB-induced delirium reported in the medical literature. We examine the use of the substance gamma hydroxybutyric acid (GHB) and describe the clinical findings in a patient who presented to an acute inpatient psychiatric unit with a chief complaint of feeling suicidal and a 1-year history of GHB use. A review of the literature and GHB's availability through the Internet are discussed.

Topics: Adjuvants, Anesthesia; Adult; Delirium; Female; Hallucinations; Humans; Mental Status Schedule; Psychoses, Substance-Induced; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Suicide; Suicide Prevention

Gamma-hydroxybutyric acid is an allegedly benign illicit substance that is gaining increasing recognition and attention among substance abusers and athletes. Alongside foreign-made brands, the compound is also easily available, at low cost because of the facility with which it can be produced in one's kitchen. Named by some "Nature's Quaalude" or sold as a health product, it is often used with a false sense of security as it may cause serious and disabling complications, as illustrated by this clinical vignette.

Topics: Anesthetics, Intravenous; Antipsychotic Agents; Hallucinations; Haloperidol; Hospitalization; Humans; Illicit Drugs; Male; Middle Aged; Psychoses, Substance-Induced; Sodium Oxybate

Topics: Anesthetics; Animals; Behavior, Animal; Brain; Cats; Diazepam; Electroencephalography; Female; Hallucinations; Humans; Hydroxybutyrates; Hypnotics and Sedatives; Pentobarbital; Reticular Formation; Sodium Oxybate