title: Flumazenil for the Treatment of Refractory Hypersomnolence: Clinical Experience with 153 Patients.
abstract: Patients with central disorders of hypersomnolence sometimes do not achieve satisfactory symptom control with currently available wake-promoting medications. Based on the finding that the cerebrospinal fluid from some patients with hypersomnolence demonstrates potentiation of gamma-aminobutyric acid (GABA)-A receptors in excess of that of controls, a finding that reverses with flumazenil, we initiated prescribing compounded flumazenil to carefully selected, treatment-refractory hypersomnolent patients.
  
  
  
  This retrospective chart review evaluated the first 153 consecutive patients treated with transdermal and/or sublingual flumazenil by physicians at our center from 2013 through January 2015.
  
  
  
  Patients were 35.5 y old (± 14.4) and 92 (60.1%) were women. Mean Epworth Sleepiness Scale scores prior to flumazenil were 15.1 (± 4.5) despite prior or current treatment with traditional wake-promoting therapies. Symptomatic benefit was noted by 96 patients (62.8%), with a mean reduction in Epworth Sleepiness Scale score of 4.7 points (± 4.7) among responders. Of these, 59 remained on flumazenil chronically, for a mean of 7.8 mo (± 6.9 mo). Female sex and presence of reported sleep inertia differentiated flumazenil responders from nonresponders. Adverse events were common, but often did not result in treatment discontinuation. Serious adverse events included a transient ischemic attack and a lupus vasculopathy, although whether these events occurred because of flumazenil administration is unknown.
  
  
  
  This chart review demonstrates that sublingual and transdermal flumazenil provided sustained clinical benefit to 39% of patients with treatment-refractory hypersomnolence. Prospective, controlled studies of this GABA-A receptor antagonist for the treatment of hypersomnolence are needed.
  
  
  
  A commentary on this article appears in this issue on page 1321.
authors: Emory University School of Medicine, Sleep Center and Department of Neurology, Atlanta, GA.
authors: Lynn Marie
authors: LM
authors: Trotti
authors: Emory University School of Medicine, Sleep Center and Department of Neurology, Atlanta, GA.|Emory University Rollins School of Public Health, Atlanta, GA.
authors: Prabhjyot
authors: P
authors: Saini
authors: Emory University Rollins School of Public Health, Atlanta, GA.
authors: Catherine
authors: C
authors: Koola
authors: Emory University School of Medicine, Sleep Center and Department of Neurology, Atlanta, GA.
authors: Vincent
authors: V
authors: LaBarbera
authors: Emory University School of Medicine, Sleep Center and Department of Neurology, Atlanta, GA.
authors: Donald L
authors: DL
authors: Bliwise
authors: Emory University School of Medicine, Sleep Center and Department of Neurology, Atlanta, GA.
authors: David B
authors: DB
authors: Rye
mesh_terms: D000328:Adult; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy*; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use*; D018757:GABA Modulators / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018757:GABA Modulators; D005442:Flumazenil
keywords: GABA-A receptor; GABA-related hypersomnia; flumazenil; hypersomnolence; idiopathic hypersomnia; narcolepsy