title: Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Gamma-hydroxybutyrate (GHB) is currently authorized by the European Medicines Agency (EMA) to treat narcolepsy with cataplexy in adults, and by the Food and Drug Administration (FDA) to treat cataplexy in patients with narcolepsy, with an expanded indication for the treatment of excessive daytime sleepiness. This study meta-analyses and reviews the effectiveness of GHB on the clinical features of narcolepsy and its neurophysiological correlates.
  
  
  METHODS
  A systematic review of the literature using Medline, Embase, Web of Science, Cochrane reviews, clinical-trials.gov, Scopus, Scirus, and a subsequent meta-analysis were performed. Considered outcomes were: cataplexy attacks, subjective daytime sleepiness, sleep attacks, clinical global impression change (CGI-c), quality of life (QoL), hypnagogic hallucinations, sleep paralysis, mean sleep latencies on the multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT), nocturnal polysomnographic data.
  
  
  RESULTS
  Nine randomized controlled trials reporting data on the effectiveness of GHB on narcolepsy were identified, for a total of 1,154 patients (771 patients in the GHB-treated group and 383 in the placebo group). The meta-analysis showed that GHB reduced cataplexy attacks both on a daily (weighted mean difference (WMD) -1.10; 95% confidence interval (CI) -1.29/-0.90, p < 0.00001) and a weekly basis (WMD -7.04; 95% CI -12.45/-1.63, p = 0.01), subjective nocturnal awakenings (WMD -1.33; 95% CI -1.78/-0.88, p < 0.00001), daytime sleep attacks on a weekly basis (WMD -9.30; 95% CI -15.92/-2.68, p = 0.006), subjective daytime sleepiness (WMD -2.81; 95% CI -4.13/-1.49, p < 0.0001) and sleep stage shifts (WMD -9.69; 95% CI -17.14/-2.24, p = 0.01). GHB increased sleep stages 3 + 4 (WMD 4.11; 95% CI 0.07/8.16, p = 0.05) and improved the CGI-c score (odds ratio (OR) 3.45; 95% CI 2.47/4.80, p < 0.00001). No significant changes were observed in night sleep latency, total sleep time, rapid-eye movement (REM) sleep and sleep stages 1 and 2.
  
  
  CONCLUSIONS
  This meta-analysis demonstrates the effectiveness of GHB in treating major, clinically relevant narcolepsy symptoms and sleep architecture abnormalities.
authors: Department of Environmental Medicine and Public Health, Section of Legal Medicine and Forensic Pathology, University of Padova, Italy. rafael.boscoloberto@unipd.it
authors: Rafael
authors: R
authors: Boscolo-Berto
authors: Guido
authors: G
authors: Viel
authors: Sara
authors: S
authors: Montagnese
authors: Daniella I
authors: DI
authors: Raduazzo
authors: Santo D
authors: SD
authors: Ferrara
authors: Yves
authors: Y
authors: Dauvilliers
mesh_terms: D000328:Adult; D002385:Cataplexy / Q000188:drug therapy / Q000503:physiopathology; D058786:GABA-B Receptor Agonists / Q000627:therapeutic use*; D006801:Humans; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D017286:Polysomnography; D016032:Randomized Controlled Trials as Topic; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D012978:Sodium Oxybate / Q000627:therapeutic use*
chemical_list: D058786:GABA-B Receptor Agonists; D012978:Sodium Oxybate