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Journal of Sleep Research Dec 2021Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based... (Review)
Review
BACKGROUND AND PURPOSE
Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children.
METHODS
The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.
RESULTS
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions.
CONCLUSION
The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Topics: Adult; Cataplexy; Child; Humans; Modafinil; Narcolepsy; Sleep; Sodium Oxybate
PubMed: 34173288
DOI: 10.1111/jsr.13387 -
Acta Psychiatrica Scandinavica Jul 2021Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and... (Review)
Review
OBJECTIVE
Narcolepsy is a rare sleep disorder in which psychotic-like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and medical management of, narcolepsy and psychosis in children and adults.
METHODS
We reviewed the full text of 100 papers from 187 identified by a PubMed search on narcolepsy plus any of these keywords: psychosis, schizophrenia, delusion, side effects, safety, and bipolar disorder.
RESULTS
Three relevant groups are described. (i) In typical narcolepsy, psychotic-like symptoms include predominantly visual hallucinations at the sleep-wake transition (experienced as "not real") and dissociation because of intrusion of rapid eye movement (REM) sleep phenomena into wakefulness. (ii) Atypical patients ("the psychotic form of narcolepsy") experience more severe and vivid, apparently REM-related hallucinations or dream/reality confusions, which patients may rationalize in a delusion-like way. (iii) Some patients have a comorbid schizophrenia spectrum disorder with psychotic symptoms unrelated to sleep. Psychostimulants used to treat narcolepsy may trigger psychotic symptoms in all three groups. We analyzed 58 published cases from groups 2 and 3 (n = 17 and 41). Features that were reported significantly more frequently in atypical patients include visual and multimodal hallucinations, sexual and mystical delusions, and false memories. Dual diagnosis patients had more disorganized symptoms and earlier onset of narcolepsy.
CONCLUSION
Epidemiological studies tentatively suggest a possible association between narcolepsy and schizophrenia only for very early-onset cases, which could be related to the partially overlapping neurodevelopmental changes observed in these disorders. We propose a clinical algorithm for the management of cases with psychotic-like or psychotic features.
Topics: Adult; Child; Hallucinations; Humans; Narcolepsy; Psychotic Disorders; Schizophrenia; Sleep, REM
PubMed: 33779983
DOI: 10.1111/acps.13300 -
Frontiers of Neurology and Neuroscience 2021Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive... (Review)
Review
Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa, age-related cognitive decline, and neurodegenerative disease. Preliminary studies suggest that orexin mimetics can safely promote the wake signal via orexin agonism during the day and that orexin receptor antagonists can promote the sleep signal during the night. Thus, novel orexin therapies have the potential to either improve memory, cognition, and daytime performance directly or indirectly, through promotion of good sleep. The full scope of the therapeutic potential of orexin therapies remains to be elucidated.
Topics: Aging; Alzheimer Disease; Animals; Anorexia Nervosa; Cognitive Dysfunction; Humans; Narcolepsy; Orexin Receptors; Orexins; Parkinson Disease; Sleep
PubMed: 34052810
DOI: 10.1159/000514960 -
International Journal of Environmental... Nov 2021Sleep disorders, especially insomnia, are very common in different kinds of cancers, but their prevalence and incidence are not well-known. Disturbed sleep in cancer is... (Review)
Review
INTRODUCTION
Sleep disorders, especially insomnia, are very common in different kinds of cancers, but their prevalence and incidence are not well-known. Disturbed sleep in cancer is caused by different reasons and usually appears as a comorbid disorder to different somatic and psychiatric diagnoses, psychological disturbances and treatment methods. There can be many different predictors for sleep disturbances in these vulnerable groups, such as pre-existing sleep disorders, caused by the mental status in cancer or as side effect of the cancer treatment.
METHODS
A systematic literature review of 8073 studies was conducted on the topic of sleep and sleep disorders in cancer patients. The articles were identified though PubMed, PsycInfo and Web of Knowledge, and a total number of 89 publications were qualified for analysis.
RESULTS
The identified eighty-nine studies were analyzed on the topic of sleep and sleep disorders in cancer, twenty-six studies on sleep and fatigue in cancer and sixty-one studies on the topic of sleep disorders in cancer. The prevalence of sleep disturbences and/or sleep disorders in cancer was up to 95%.
DISCUSSION
Sleep disturbances and sleep disorders (such as insomnia, OSAS, narcolepsy and RLS; REM-SBD) in cancer patients can be associated with different conditions. Side effects of cancer treatment and cancer-related psychological dysfunctions can be instigated by sleep disturbances and sleep disorders in these patients, especially insomnia and OSAS are common. An evidence-based treatment is necessary for concomitant mental and/or physical states.
Topics: Humans; Narcolepsy; Neoplasms; Restless Legs Syndrome; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 34770209
DOI: 10.3390/ijerph182111696 -
The AAPS Journal Jan 2021Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate,... (Review)
Review
Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid present endogenously in the brain and used therapeutically for the treatment of narcolepsy, as sodium oxybate, and for alcohol abuse/withdrawal. GHB is better known however as a drug of abuse and is commonly referred to as the "date-rape drug"; current use in popular culture includes recreational "chemsex," due to its properties of euphoria, loss of inhibition, amnesia, and drowsiness. Due to the steep concentration-effect curve for GHB, overdoses occur commonly and symptoms include sedation, respiratory depression, coma, and death. GHB binds to both GHB and GABA receptors in the brain, with pharmacological/toxicological effects mainly due to GABA agonist effects. The pharmacokinetics of GHB are complex and include nonlinear absorption, metabolism, tissue uptake, and renal elimination processes. GHB is a substrate for monocarboxylate transporters, including both sodium-dependent transporters (SMCT1, 2; SLC5A8; SLC5A12) and proton-dependent transporters (MCT1-4; SLC16A1, 7, 8, and 3), which represent significant determinants of absorption, renal reabsorption, and brain and tissue uptake. This review will provide current information of the pharmacology, therapeutic effects, and pharmacokinetics/pharmacodynamics of GHB, as well as therapeutic strategies for the treatment of overdoses. Graphical abstract.
Topics: Alcoholism; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Overdose; Humans; Hydroxybutyrates; Metabolic Clearance Rate; Narcolepsy; Sodium Oxybate; Substance Abuse, Oral; Substance Withdrawal Syndrome
PubMed: 33417072
DOI: 10.1208/s12248-020-00543-z -
CNS Drugs Jan 2020Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for... (Review)
Review
Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medications that inhibit serotonin or norepinephrine reuptake have anticataplectic effects. Modulation of γ-aminobutyric acid B (GABA) receptors or histamine H receptors (H3Rs) has effects on both EDS and cataplexy. Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy; these agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy.
Topics: Animals; Central Nervous System Stimulants; Humans; Narcolepsy
PubMed: 31953791
DOI: 10.1007/s40263-019-00689-1 -
Science (New York, N.Y.) Feb 2022Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep...
Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity.
Topics: Aging; Aminopyridines; Animals; CRISPR-Cas Systems; Electroencephalography; Electromyography; Female; Hypothalamic Area, Lateral; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Male; Mice; Narcolepsy; Nerve Tissue Proteins; Neural Pathways; Neurons; Optogenetics; Orexins; Patch-Clamp Techniques; RNA-Seq; Sleep; Sleep Deprivation; Sleep Quality; Wakefulness
PubMed: 35201886
DOI: 10.1126/science.abh3021 -
Neurotherapeutics : the Journal of the... Jan 2021The recent trend for legalization of medicinal cannabis and cannabinoid-containing products, together with their soporific effects, has led to a surge of interest of... (Review)
Review
The recent trend for legalization of medicinal cannabis and cannabinoid-containing products, together with their soporific effects, has led to a surge of interest of their potential therapeutic role in the management of some common sleep disorders, such as insomnia, sleep disordered breathing, and restless legs syndrome, and less common disorders such as narcolepsy and parasomnias. Although much of the pre-clinical and clinical data were derived from studies with relatively small sample sizes and limited by biases in assessment, and in clinical trials lack of allocation concealment, as a whole, the results indicate a potential therapeutic role for cannabinoids in the management of some sleep disorders. Clinical trials are underway for insomnia and obstructive sleep apnea management, but there remains a substantial need for rigorous large multi-center studies to assess the dose, efficacy, and safety of the various types of cannabinoids on sleep disorders. This review aims to summarize the modulatory effects of cannabinoids on sleep physiology and provide a critical evaluation of the research on their potential therapeutic benefit in various sleep disorders.
Topics: Cannabinoids; Humans; Sleep; Sleep Wake Disorders
PubMed: 33580483
DOI: 10.1007/s13311-021-01013-w