Medications for the treatment of narcolepsy.
Narcolepsy is a syndrome of unknown aetiology characterised by excessive daytime sleepiness (often severe) usually in association with cataplexy (brief episodes of partial or complete muscle paralysis) and often with other uncommon symptoms. Due to limited disease-specific knowledge, medication treatment for this condition has focussed on specific symptom amelioration rather than improving or eliminating underlying disease mechanisms. Such treatment generally consists of stimulants for daytime sleepiness and anticataplectic medication for cataplexy; hence, both types of agents are reviewed in this article. Recent discoveries, including the finding that canine familial narcolepsy is caused by a single gene defect in the hypocretin receptor, coupled with the findings in human narcoleptics of undetectable hypocretin levels in the CSF and of severe hypocretin-containing neuronal atrophy in brains of deceased narcoleptics, have shifted the focus of narcolepsy treatment research to the hypocretin system. The hope is that a single agent can be developed to provide effective treatment for all symptoms of narcolepsy. While the mechanism of action in narcolepsy is unknown, gamma-hydroxybutyrate (GHB) is proving to be such an agent. Interestingly, GHB is not known to impact hypocretin pathways in the brain, yet specific research exploring this possible interaction has not been performed. The market for medications limited to use by narcoleptics is small because of the relatively low prevalence of narcolepsy; however, the prevalence of clinically important daytime sleepiness and/or fatigue is surprisingly high. New agents that effectively manage the sleepiness of narcolepsy thus have a much larger potential for appropriate use in treating sleepiness and fatigue in the general population. This fact has recently been demonstrated by the tremendous success of modafinil, a drug introduced to the market a little over 2 years ago, which was developed to treat sleepiness in narcolepsy but now is used in a much larger patient population.
Black
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Stanford Sleep Disorders Clinic, 401, Quarry Road, Suite 3301, Stanford, CA 94305, USA. majorsleep@yahoo.com
Guilleminault
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