title: Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience.
abstract: The macrolide antibiotic clarithromycin can enhance central nervous system excitability, possibly by antagonism of GABA-A receptors. Enhancement of GABA signaling has recently been demonstrated in a significant proportion of patients with central nervous system hypersomnias, so we sought to determine whether clarithromycin might provide symptomatic benefit in these patients. We performed a retrospective review of all patients treated with clarithromycin for hypersomnia, in whom cerebrospinal fluid enhanced GABA-A receptor activity in vitro in excess of controls, excluding those with hypocretin deficiency or definite cataplexy. Subjective reports of benefit and objective measures of psychomotor vigilance were collected to assess clarithromycin's effects. Clinical and demographic characteristics were compared in responders and non-responders. In total, 53 patients (38 women, mean age 35.2 (SD 12.8 years)) were prescribed clarithromycin. Of these, 34 (64%) reported improvement in daytime sleepiness, while 10 (19%) did not tolerate its side effects, and nine (17%) found it tolerable but without symptomatic benefit. In those who reported subjective benefit, objective corroboration of improved vigilance was evident on the psychomotor vigilance task. Twenty patients (38%) elected to continue clarithromycin therapy. Clarithromycin responders were significantly younger than non-responders. Clarithromycin may be useful in the treatment of hypersomnia associated with enhancement of GABA-A receptor function. Further evaluation of this novel therapy is needed.
authors.affiliation: Department of Neurology and Emory Program in Sleep, Emory University School of Medicine, Atlanta, GA, USA Lbecke2@emory.edu.
authors.forename: Lynn Marie
authors.initials: LM
authors.lastname: Trotti
authors.affiliation: Department of Neurology and Emory Program in Sleep, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Prabhjyot
authors.initials: P
authors.lastname: Saini
authors.affiliation: Department of Neurology and Emory Program in Sleep, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Freeman
authors.affiliation: Department of Neurology and Emory Program in Sleep, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Bliwise
authors.affiliation: Department of Anesthesia, Emory University School of Medicine, Atlanta, GA, USA Atlanta VA Medical Center, Atlanta, GA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: García
authors.affiliation: Department of Anesthesia, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Department of Neurology and Emory Program in Sleep, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Rye
mesh_terms: D000328:Adult; D017291:Clarithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D011963:Receptors, GABA-A; D064690:Wakefulness-Promoting Agents; D017291:Clarithromycin
keywords: Clarithromycin; GABA-A; excessive daytime sleepiness; hypersomnia; idiopathic hypersomnia; narcolepsy