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Cleveland Clinic Journal of Medicine Dec 2018Narcolepsy is a chronic disorder of hypersomnia that can have a significant impact on quality of life and livelihood. However, with appropriate treatment, its symptoms... (Review)
Review
Narcolepsy is a chronic disorder of hypersomnia that can have a significant impact on quality of life and livelihood. However, with appropriate treatment, its symptoms are manageable, and a satisfying personal, social, and professional life can still be enjoyed. Greater awareness of the disorder promotes accurate and efficient diagnosis. With ongoing research into its underlying biology, better treatments for narcolepsy will inevitably become available.
Topics: Disease Management; Humans; Narcolepsy
PubMed: 30526757
DOI: 10.3949/ccjm.85a.17086 -
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 -
Nature Reviews. Neuroscience Feb 2019Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons... (Review)
Review
Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons producing orexins (also known as hypocretins) sparked great advances in the field. Here, we review the current understanding of how orexin neurons regulate sleep-wake behaviour and the consequences of the loss of orexin neurons. We also summarize the developing evidence that narcolepsy is an autoimmune disorder that may be caused by a T cell-mediated attack on the orexin neurons and explain how these new perspectives can inform better therapeutic approaches.
Topics: Animals; Autoimmune Diseases; Humans; Narcolepsy; Nervous System; Neurobiology; Orexins
PubMed: 30546103
DOI: 10.1038/s41583-018-0097-x -
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 -
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 -
European Journal of Neurology Sep 2021Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based...
BACKGROUND AND AIM
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 in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (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: 34173695
DOI: 10.1111/ene.14888 -
Annals of Neurology Mar 2019Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adult; Carbamates; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcolepsy; Phenylalanine; Sleep Latency; Sleepiness; Treatment Outcome; Wakefulness-Promoting Agents; Young Adult
PubMed: 30694576
DOI: 10.1002/ana.25423 -
Journal of Clinical Sleep Medicine :... Sep 2021This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
INTRODUCTION
This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.
RECOMMENDATIONS
The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment.
1
We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG).
2
We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG).
3
We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG).
4
We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG).
5
We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL).
6
We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL).
7
We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL).
8
We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG).
9
We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
10
We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
11
We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
12
We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
13
We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL).
14
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL).
15
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
16
We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
17
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
18
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
19
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL).
20
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL).
21
We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
22
We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. . 2021;17(9):1881-1893.
Topics: Adult; Child; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Modafinil; Narcolepsy; Sleep; United States
PubMed: 34743789
DOI: 10.5664/jcsm.9328 -
The Neuroscientist : a Review Journal... Aug 2020Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis... (Review)
Review
Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.
Topics: Animals; Disorders of Excessive Somnolence; Humans; Kleine-Levin Syndrome; Narcolepsy; Nervous System Diseases; Neuroimaging; Sleep
PubMed: 32111133
DOI: 10.1177/1073858420905829 -
Cell Aug 1999Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central... (Comparative Study)
Comparative Study
Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep regulation. Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only known monogenic model of narcolepsy. Moreover, modafinil, an anti-narcoleptic drug with ill-defined mechanisms of action, activates orexin-containing neurons. We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.
Topics: Age of Onset; Animals; Benzhydryl Compounds; Carrier Proteins; Disease Models, Animal; Dog Diseases; Dogs; Electroencephalography; Electromyography; Humans; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Modafinil; Narcolepsy; Neurons; Neuropeptides; Orexin Receptors; Orexins; Phenotype; Posture; Protein Precursors; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Sleep; Sleep, REM; Species Specificity; Stereotyped Behavior
PubMed: 10481909
DOI: 10.1016/s0092-8674(00)81973-x