title: Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial.
abstract: OBJECTIVE
  Some central hypersomnolence syndromes are associated with a positive allosteric modulator of γ-aminobutyric acid (GABA)-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness.
  
  
  METHODS
  This was a 5-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Quality Index, SF-36, and additional PVT measures.
  
  
  RESULTS
  Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on 20 complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred.
  
  
  CONCLUSIONS
  Subjective sleepiness, but not psychomotor vigilance, improved during a 2-week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence. This trial was registered at ClinicalTrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation.
authors.affiliation: Department of Neurology and Emory Sleep Center.
authors.forename: Lynn Marie
authors.initials: LM
authors.lastname: Trotti
authors.affiliation: Department of Neurology and Emory Sleep Center.
authors.forename: Prabhjyot
authors.initials: P
authors.lastname: Saini
authors.affiliation: Department of Neurology and Emory Sleep Center.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Bliwise
authors.affiliation: Department of Neurology and Emory Sleep Center.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Freeman
authors.affiliation: Department of Anesthesia, Emory University School of Medicine, Atlanta, GA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Department of Neurology and Emory Sleep Center.
authors.forename: David B
authors.initials: DB
authors.lastname: Rye
mesh_terms: D000328:Adult; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid*
chemical_list: D005680:gamma-Aminobutyric Acid; D017291:Clarithromycin