Sodium oxybate

Sodium oxybate, sold under the brand name Xyrem among others, is a medication used to treat symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness. It is used sometimes in France and Italy as an anesthetic given intravenously. It is also approved and used in Italy and in Austria to treat alcohol dependence and alcohol withdrawal syndrome.

Sodium oxybate is the sodium salt of γ-hydroxybutyric acid (GHB). The clinical trials for narcolepsy were conducted just as abuse of GHB as a club drug and date rape drug became a matter of public concern. In 2000, GHB was made a Schedule I controlled substance in the United States, while sodium oxybate, when used under an FDA New Drug Application or Investigative New Drug application, was classified as a Schedule III controlled substance for medicinal use under the Controlled Substances Act, with illicit use subject to Schedule I penalties.

Sodium oxybate was approved for use by the US Food and Drug Administration (FDA) to treat symptoms of narcolepsy in 2002, with a strict risk evaluation and mitigation strategy (REMS) program mandated by the FDA. The US label for sodium oxybate also has a black box warning because it is a central nervous system (CNS) depressant and may cause respiratory depression, seizures, coma, or death, especially if used in combination with other CNS depressants such as alcohol, and its use may cause dependence. In Canada and the European Union it was classified as a Schedule III and a Schedule IV controlled substance, respectively.

It was approved for treating symptoms of narcolepsy in the European Union in 2005.

Orphan Medical had developed it and was acquired by Jazz Pharmaceuticals in 2005. The drug is marketed in Europe by UCB. Jazz Pharmaceuticals raised the price of the drug dramatically after it acquired Orphan, and paid a $20M fine for off-label marketing of the drug in 2007.

Clinical use of sodium oxybate was introduced in Europe in 1964 as an anesthetic given intravenously, but it was not widely used since it sometimes caused seizures. As of 2006, it was still authorized for this use in France and Italy but not widely used.

The major use of sodium oxybate is in treating two of the symptoms of narcolepsy – cataplexy (sudden muscle weakness) and excessive daytime sleepiness. Reviews of sodium oxybate concluded that it is well tolerated and associated with "significant reductions in cataplexy and daytime sleepiness", and that its effectiveness "in treating major, clinically relevant narcolepsy symptoms and sleep architecture abnormalities" has been established. However, because of the risks of abuse associated with this medication, it is available in the US only through a REMS program mandated by the FDA. The program requires that providers who prescribe it are certified to do so, that it is dispensed only from a central pharmacy that is certified to do so, and that people to whom it is prescribed must be enrolled in a program for the drug and must document that they are using the drug safely.

Investigations of its use in dealing with alcohol withdrawal syndrome and in the maintenance of abstinence began in 1989 in Italy, where it was then approved in these indications in 1991. It has also been approved for use in Austria. Over the years, several studies were conducted to further substantiate sodium oxybate efficacy in these indications. Results of small studies suggest it may be "better than naltrexone and disulfiram regarding abstinence maintenance and prevention of craving in the medium term, i.e. 3–12 months." In a 2014 review, Gillian Keating described sodium oxybate as a "useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence." However, a 2018 review recognised the evidence for its efficacy but noted safety concerns and concluded that "studies are still limited and investigations including a larger number of patients are needed."