Sodium oxybate: Efficacy, safety and tolerability in the treatment of narcolepsy with or without cataplexy

Abstract

Sodium oxybate is the sodium salt of gamma- hydroxybutyrate, an endogenous cerebral inhibitory neurotransmitter. It is licensed in the United States for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy and in the European Union for the treatment of narcolepsy with cataplexy. Its mode of action is uncertain, but it increases 5-hydroxytryptamine turnover, interacts with opioid systems and may act as a gamma-aminobutyric acid B receptor agonist (GABA(B)). It is rapidly absorbed and eliminated, having a mean elimination half-life of 30-60 minutes. In controlled trials in narcolepsy without cataplexy, it decreased excessive daytime sleepiness and increased several quality of life domains. In combination with modafinil, it exerted an additive effect in diminishing daytime sleepiness. Both acute (four to eight weeks) and chronic (12 months) studies have demonstrated sodium oxybate's efficacy in decreasing cataplectic attack frequency. It is well tolerated with adverse event withdrawal rates of approximately 3-10% after acute and chronic administration. There is no clear evidence of a withdrawal syndrome after abrupt cessation of therapeutic doses. Sodium oxybate appears to be an effective and well-tolerated treatment for all the key symptoms of the two forms of narcolepsy.