However, this scarcity has eased, and dozens of people are now being treated with flumazenil off-label. Clarithromycin
In a test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to return the function of the GABA system to normal in people with primary hypersomnias. Investigators therefore treated a few people with narcolepsy with off-label clarithromycin, and most felt their symptoms improved with this treatment. In order to help further determine whether clarithromycin is truly beneficial for the treatment of narcolepsy and idiopathic hypersomnia, a small, double-blind, randomized, controlled clinical trial was completed in 2012. "In this pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. Larger trials of longer duration are warranted." In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of people with GABA-related hypersomnia. "It is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained." Orexin receptor agonists
Orexin-A (a.k.a. hypocretin-1) has been shown to be strongly wake-promoting in animal models, but it does not cross the blood–brain barrier. The first line treatment for narcolepsy, modafinil, has been found to interact indirectly with the orexin system. It is also likely that an orexin receptor agonist will be found and developed for the treatment of hypersomnia. One such agent which is currently in clinical trials is danavorexton. L-carnitine
Abnormally low levels of acylcarnitine have been observed in people with narcolepsy.
In addition, the hypersomnolence and sleep latency findings cannot be better explained by other causes.DSM-5 narcolepsy criteria requires that the person to display recurrent periods of "an irrepressible need to sleep, lapsing into sleep, or napping" for at least three times a week over a period of three months. The individual must also display one of the following: cataplexy, hypocretin-1 concentration of less than 110 pg/mL, REM sleep latency of less than 15 minutes, or a multiple sleep latency test (MSLT) showing sleep latency of less than 8 minutes and two or more SOREMPs. For a diagnosis of hypersomnolence disorder, the individual must present with excessive sleepiness despite at least 7 hours of sleep as well as either recurrent lapses into daytime sleep, nonrestorative sleep episodes of 9 or more hours, or difficulty staying awake after awakening. In addition, the hypersomnolence must occur at least three times a week for a period of three months, and must be accompanied by significant distress or impairment. It also cannot be explained by another sleep disorder, coexisting mental or medical disorders, or medication. Tests
Diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. Three tests that are commonly used in diagnosing narcolepsy are polysomnography (PSG), the multiple sleep latency test (MSLT), and the Epworth Sleepiness Scale (ESS).