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

• Type of Material: Article
• Authors: Lynn Trotti, Emory University; Prabhjyot Saini, Emory University; Donald Bliwise, Emory University; Amanda Freeman, Emory University; Andrew Jenkins, Emory University; David Rye, Emory University
• Language: English
• Date: 2015-09-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Neurological Association.
• Final Published Version (URL): http://dx.doi.org/10.1002/ana.24459
• Title of Journal or Parent Work: Annals of Neurology
• ISSN: 0364-5134
• Volume: 78
• Issue: 3
• Start Page: 454
• End Page: 465
• Grant/Funding Information: This research project was made possible by a grant from the American Sleep Medicine Foundation, a foundation of the American Academy of Sleep Medicine.; Dr. Trotti received additional support from NINDS K23 NS083748.; 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.
• Keywords: NARCOLEPSY; PERFORMANCE; QUALITY-OF-LIFE; IDIOPATHIC HYPERSOMNIA; MODAFINIL; CENTRAL ORIGIN; Life Sciences & Biomedicine; DOUBLE-BLIND; DAYTIME SLEEPINESS; PLACEBO; Neurosciences; Science & Technology; Neurosciences & Neurology; Clinical Neurology; LONG-SLEEP TIME
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

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. 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.