title: Time to response with sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy.
abstract: OBJECTIVE
  This post hoc analysis evaluated the time to response that can be expected with sodium oxybate (SXB) for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy.
  
  
  METHODS
  Data were from a 4-week, double-blind, randomized, placebo-controlled trial (GHB-2; N = 136) of oral SXB 3 g, 6 g, and 9 g nightly, and its 12-month open-label extension (GHB-3). Two response definitions were utilized: ≥ 20% improvement in Epworth Sleepiness Scale (ESS) score (EDS responders), and ≥ 50% reduction in weekly cataplexy attacks (cataplexy responders). These thresholds were previously determined to be clinically relevant based on analysis of the relationship of Clinical Global Impression of Change with ESS and number of cataplexy attacks. Kaplan-Meier curves and median times to first response, based on above criteria, and to maximum response were estimated.
  
  
  RESULTS
  Among 86 patients randomized to SXB in GHB-2 and continued into GHB-3, 77.6% and 90.7% were EDS and cataplexy responders, respectively. The median (95% CI) times to first response were 37 (31-50) days for EDS and 25 (17-29) days for cataplexy, and median times to maximum response were 106 (85-164) days for EDS and 213 (94-279) days for cataplexy. GHB-3 results among 31 patients initially randomized to placebo were consistent with those treated with SXB throughout, but with longer times to maximum response.
  
  
  CONCLUSIONS
  Response onset, assessed as clinically meaningful improvements in EDS and cataplexy, was observed in most patients within 2 months; a longer period is needed to achieve maximum response. Clinicians should recognize that time to initial and maximum response may take weeks to months.
authors.affiliation: University of South Carolina School of Medicine, Columbia, SC.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Bogan
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: University of Oklahoma Health Services Center, Oklahoma City, OK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Jazz Pharmaceuticals, Inc., Palo Alto, CA.
authors.forename: Maja
authors.initials: M
authors.lastname: Miloslavsky
mesh_terms: D000328:Adult; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D009290:Narcolepsy / Q000188:drug therapy*; D012978:Sodium Oxybate / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; D012978:Sodium Oxybate
keywords: cataplexy; excessive daytime sleepiness; narcolepsy; sodium oxybate; time to response