Narcolepsy Treatment

There are several treatments approved by the FDA for use in narcolepsy. There are no treatments approved for idiopathic hypersomnia (IHS), although it is common practice to use wake-promoting medications that are known to be effective in patients with narcolepsy to treat the sleepiness associated with idiopathic hypersomnia. These treatments have not been studied to nearly the same extent in patients with idiopathic hypersomnia, and some patients with IHS do not achieve adequate control of symptoms with these medications.


There are three major classes of medications approved for the treatment of sleepiness associated with narcolepsy: stimulant medications (i.e., derivatives of amphetamines), non-stimulant wake-promoting medications (e.g., modafinil and armodafinil), and sodium oxybate.  Stimulants approved for the treatment of sleepiness in narcolepsy include dextroamphetamine and methylphenidate (e.g., Ritalin).  While stimulants may be effective, potential side effects include dependence, aggressive behavior, and heart problems.  Non-stimulant medications include modafinil and armodafinil.  While the mechanism of action of these medications is not completely known, they appear to influence brain chemistry that increases wakefulness.  Modafinil and armodafinil can interact with hormonal birth control to make it less effective, can result in a life-threatening rash, and are sometimes limited by associated headache.  Sodium oxybate is medication taken at bedtime (and again during the night) that promotes deep sleep and improves daytime sleepiness in patients with narcolepsy; its effects in those with idiopathic hypersomnia are not well characterized.  Of the medications listed above, sodium oxybate is the only medication that treats both sleepiness and cataplexy.


Sodium oxybate is the only medication approved for cataplexy.  Antidepressants, especially serotonin and norepinephrine reuptake inhibitors, are frequently used “off label” to treat cataplexy.


As the brain systems regulating sleepiness and wakefulness are better understood, scientists will be in a better position to design treatments that target key portions of this system.  For example, based on the role of histamine in keeping people awake (and hence the common side effect of anti-histamines such as diphenhydramine causing sleepiness), medications that act on histamine are under development for the treatment of excessive sleepiness.  In the case of the primary hypersomnias related to excess activity of the GABA system, medications that could counteract this activity have potential to improve sleepiness.  Dr. David Rye and colleagues have recently reported that use of flumazenil, one such medication, results in improvements in sleepiness when given intravenously.  Two double-blind, randomized controlled clinical trials of medications that appear to influence GABA activity have recently been completed at Emory University and results should be available soon.


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