Abstract
Narcolepsy is a complex disease with multiple symptoms that include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Pharmacologic management of patients with narcolepsy is based on treating these symptoms. Sodium oxybate, a neurotransmitter product of γ-amino butyric acid (GABA), is a Schedule III controlled substance in the US, approved for the treatment of excessive daytime sleepiness (EDS), and cataplexy in patients with narcolepsy. The purpose of this review is to summarize the current knowledge about treatment of narcolepsy with sodium oxybate and to familiarize readers with the safety and efficacy of sodium oxybate, thus enabling clinicians to optimize their management of narcolepsy. A review of the pharmacokinetics, pharmacodynamics, efficacy in different symptoms of narcolepsy, adverse effects, tolerability, and dosing of sodium oxybate is presented. Sodium oxybate administered as an oral solution has a rapid onset of effect, a short duration of action, and nearly complete metabolism with negligible unchanged γ-hydroxybutyrate (GHB) appearing in the urine. There is mounting evidence suggesting that GHB may function as an endogenous neuromodulator/neurotransmitter. The mechanism by which sodium oxybate has a therapeutic effect in narcolepsy is unclear. The efficacy of oral sodium oxybate on the treatment of narcolepsy was evaluated in two randomized, double-blind, placebo- controlled, multicenter, US and International trials. Treatment of patients with narcolepsy-cataplexy with sodium oxybate leads to reduction in the frequency of cataplexy attacks in a dose-related manner, improved EDS, increased level of alertness and ability to concentrate. The major problem with sodium oxybate remains in its potential for non-medical use to elicit altered states of consciousness; however, abuse and misuse of sodium oxybate has been rare over the 7 years since its introduction in the market. Other issues revolve around twice nightly dosing, and salty taste. The most commonly reported adverse events associated with the use of sodium oxybate and occurring with at least 5% greater frequency than seen in placebo-treated patients were dizziness, headache, nausea, pain, night terrors, enuresis, confusion, infection, vomiting, and urinary incontinence. In conclusion, sodium oxybate significantly improves all symptoms in patients with narcolepsy and is well tolerated.
Highlights
Narcolepsy is an uncommon life-long condition that is often under-recognized, especially in children, and is associated with significant impairment in quality of life.[1,2]. It is a disorder of Rapid Eye Movement (REM) sleep that is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and fragmented night sleep.[1,3]
The improvements in cataplexy are dependent on the dosage of sodium oxybate as well on the duration of treatment
In sodium oxybate (SO) group, there was no decrease in Sleep Latency (SL) [⇒SO was as efficacious in treating the excessive daytime sleepiness (EDS) as the previously administered modafinil]
Summary
Narcolepsy is an uncommon life-long condition that is often under-recognized, especially in children, and is associated with significant impairment in quality of life.[1,2] It is a disorder of Rapid Eye Movement (REM) sleep that is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and fragmented night sleep.[1,3] Of the varied symptoms that may compromise the narcolepsy syndrome, excessive daytime sleepiness is ubiquitous. The authors concluded that in addition to its established efficacy in the treatment of cataplexy and EDS, nightly sodium oxybate administration significantly reduces measures of sleep disruption and significantly increases slow-wave sleep in patients with narcolepsy. The therapeutic effects of GHB in narcoleptic patients do not appear to be due to a general sedative/ hypnotic effect per se, rather, it may be due to a specific increase in delta power and duration of slow wave sleep.[34] A recent clinical trial showed that GHB and baclofen increased EEG delta activity during nocturnal sleep, only GHB reduced subjective daytime sleepiness and attacks of cataplexy.[66]. During the extension of this study more than 80% were classified as very much/much improved
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