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Author Notes:

Corresponding Author: LM Trotti, 1841 Clifton Rd Ne, Atlanta, GA 30329, Lbecke2@emory.edu, 404-728-4752 (phone), 404-712-8145 (fax).

Please see the full article for author contributions, potential conflicts of interest, and acknowledgments.

The funder [ASMF] specified that the work must be published in abstract form at its completion, but had no role in study design, data collection, data analysis, decision to publish in manuscript form, or preparation of the manuscript.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Research Funding:

This research project was made possible by a grant from the American Sleep Medicine Foundation, a foundation of the American Academy of Sleep Medicine.

Statistical consultation was provided through a program supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.

Dr. Trotti received additional support from NINDS K23 NS083748.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology

Clarithromycin in γ-aminobutyric acid–related hypersomnolence: A randomized, crossover trial


Journal Title:

Annals of Neurology


Volume 78, Number 3


, Pages 454-465

Type of Work:

Article | Post-print: After Peer Review


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. Interpretation: 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.

Copyright information:

© 2015 American Neurological Association.

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