Sodium Oxybate for Narcolepsy with Cataplexy: Systematic Review and Meta-Analysis

University Sleep Disorders Center, King Saud University, Riyadh, Saudi Arabia.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine (Impact Factor: 3.05). 08/2012; 8(4):451-8. DOI: 10.5664/jcsm.2048
Source: PubMed


To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients.
Systematic review and meta-analysis.
Adults with narcolepsy-cataplexy.
Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the efficacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1).
Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.

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Available from: Ahmed Salem BaHammam, Jun 30, 2014
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    ABSTRACT: Introduction: Narcolepsy is a rare disorder classified as hypersomnia of central origin. Its core symptoms are excessive daytime sleepiness (EDS) and cataplexy. Associated symptoms, hypnagogic hallucinations, sleep paralysis, automatic behavior, and sleep fragmentation, are unspecific. Genetic, autoimmune, and environmental factors contribute to hypocretin deficiency. Areas covered: This article focuses on therapies for narcolepsy symptoms and comorbid disorders. Despite the enormous increase of knowledge about narcolepsy's pathologies no substance has been developed that can cure the disease. So far hypocretin substitution is not available. Substances targeting the autoimmune mechanism have failed to show objective improvement despite subjective improvement. The standard medication in adults comprises stimulants and anticataplectics. Only few substances are capable of improving core and associated symptoms. Within the last years, only modafinil and its enantiomer armodafinil and sodium oxybate have been approved as new substances. Expert opinion: The choice of stimulants to treat excessive daytime sleepiness in narcolepsy needs to be expanded and anticataplectic medication needs to be approved for the indication. Head-to-head comparisons between the established medications, studies of high evidence in older non-evidence-based medications, in children, pregnant women, and of behavioral therapy need to be performed including the long-term effects on metabolic and cardiovascular risks. Narcolepsy is a model disease for so many sleep disorders, among which it has the most severe daytime sleepiness. New insights into its etiology have advanced sleep medicine immensely. Still it stays an orphan in terms of treatment options which are challenging because narcolepsy covers so many symptoms from neuropsychological metabolic-, cardiovascular-, endocrinological-, movement disorders, and parasomnias to name a few.
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