Emerging treatments for narcolepsy and its related disorders.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nishino
Seiji
S
Stanford University School of Medicine, USA. nishino@Stanford.edu
Okuro
Masashi
M
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D002385:Cataplexy / Q000150:complications / Q000188:drug therapy*; D017690:Cell Transplantation / Q000379:methods; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods; D006212:Hallucinations / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000187:drug effects / Q000627:therapeutic use; D009290:Narcolepsy / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D009479:Neuropeptides / Q000172:deficiency / Q000187:drug effects / Q000627:therapeutic use; D000068797:Orexins; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D020188:Sleep Paralysis / Q000188:drug therapy*; D012978:Sodium Oxybate / Q000627:therapeutic use; D014851:Wakefulness / Q000187:drug effects
D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D015507:Drugs, Investigational; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D012978:Sodium Oxybate