Document Detail


Expert opinion on pharmacotherapy of narcolepsy.
MedLine Citation:
PMID:  20426704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE TO THE FIELD: Narcolepsy is a neurodegenerative disorder resulting in the instability of the sleep-wake cycle and marked by low levels of hypocretin in cerebrospinal fluid. Sleep instability is marked by brisk, sleep-onset REM periods and sleep fragmentation, while the waking state is interrupted by the intrusion of REM sleep and sometimes accompanied by cataplectic attacks.
AREAS COVERED IN THIS REVIEW: Current pharmacologic interventions that aim to address three primary features of this disorder; excessive daytime sleepiness (EDS), cataplexy and automatic behaviors, and sleep fragmentation. We review and compare the use of traditional and new stimulants in the treatment of EDS. For the treatment of cataplexy and automatic behaviors, serotonergic and noradrenergic agents are considered. The role of gamma-hydroxybutyrate (GHB) is also explored in its ability to reduce daytime sleepiness and catapletic attacks and to consolidate sleep. Findings are based on a PubMed literature search of clinical and basic science research papers spanning 1977-2009.
WHAT THE READER WILL GAIN: A comprehensive understanding of the various existing and promising future treatments for narcolepsy. For each of these treatments, we evaluate risks versus benefits of treatment, and proposed pharmacologic mechanisms of action. We conclude with a review of new treatment approaches, including thyrotropin-releasing hormone (TRH), histamine agonists, immunotherapy and hypocretin replacement therapies.
TAKE HOME MESSAGE: Narcolepsy is an autoimmune, neurodegenerative disorder that results in significant sleep-wake instability with or without cataplectic attacks. Current treatments aim symptomatically to reconsolidate the sleep and waking states and to reduce daytime attacks of cataplexy. Future treatments aim primarily towards correcting the causal deficiency of hypocretin or preventing the autoimmune response that results in the loss of hypocretin cells.
Authors:
Mia Zaharna; Alex Dimitriu; Christian Guilleminault
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on pharmacotherapy     Volume:  11     ISSN:  1744-7666     ISO Abbreviation:  Expert Opin Pharmacother     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-08-02     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  100897346     Medline TA:  Expert Opin Pharmacother     Country:  England    
Other Details:
Languages:  eng     Pagination:  1633-45     Citation Subset:  IM    
Affiliation:
Stanford Medical Outpatient Center, Sleep Medicine Division MC5704, Stanford University, Redwood City, Stanford, CA 94063, USA.
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MeSH Terms
Descriptor/Qualifier:
Antidepressive Agents, Tricyclic / therapeutic use
Benzhydryl Compounds / therapeutic use
Caffeine / therapeutic use
Central Nervous System Stimulants / therapeutic use
Humans
Hypnotics and Sedatives / therapeutic use
Immunotherapy
Intracellular Signaling Peptides and Proteins / genetics,  therapeutic use
Narcolepsy / diagnosis,  drug therapy*,  genetics
Neuropeptides / genetics,  therapeutic use
Serotonin Uptake Inhibitors / therapeutic use
Sodium Oxybate / therapeutic use
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Tricyclic; 0/Benzhydryl Compounds; 0/Central Nervous System Stimulants; 0/Hypnotics and Sedatives; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Serotonin Uptake Inhibitors; 0/orexins; 502-85-2/Sodium Oxybate; 58-08-2/Caffeine; 68693-11-8/modafinil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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