However, usage now does exist in various nations such as in France, United Kingdoms (NHS as of September 2016) after being given marketing authorisation by European Commission on the advice of the European Medicines Agency and in the United States by the approval of the Food and Drug Administration (FDA) as of August 2019. GABA-directed medications
Given the possible role of hyper-active GABAA receptors in the primary hypersomnias (narcolepsy and idiopathic hypersomnia), medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil. Flumazenil
Flumazenil is the only GABAA receptor antagonist on the market as of Jan 2013, and it is currently manufactured only as an intravenous formulation. Given its pharmacology, researchers consider it to be a promising medication in the treatment of primary hypersomnias. Results of a small, double-blind, randomized, controlled clinical trial were published in November 2012. This research showed that flumazenil provides relief for most people whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA. For one person, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several years. A 2014 case report also showed improvement in primary hypersomnia symptoms after treatment with a continuous subcutaneous flumazenil infusion. The supply of generic flumazenil was initially thought to be too low to meet the potential demand for treatment of primary hypersomnias.
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affected also experience episodes of sudden loss of muscle strength, known as cataplexy. Narcolepsy paired with cataplexy is evidenced to be an autoimmune disorder. These experiences of cataplexy can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move (sleep paralysis) while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without, but the quality of sleep tends to be lessened.Narcolepsy is a clinical syndrome of hypothalamic disorder, however, the exact cause of narcolepsy is unknown, with potentially several causes. In up to 10% of cases, there is a family history of the disorder. Often, those affected have low levels of the neuropeptide orexin, which may be due to an autoimmune disorder triggered in genetically susceptible individuals by infection with H1N1 influenza. In rare cases, narcolepsy can be caused by traumatic brain injury, tumors, or other diseases affecting the parts of the brain that regulate wakefulness or REM sleep. Diagnosis is typically based on the symptoms and sleep studies, after ruling out other potential causes. Excessive daytime sleepiness can also be caused by other sleep disorders such as sleep apnea, major depressive disorder, anemia, heart failure, drinking alcohol and not getting enough sleep.