title: The Effect of Donepezil on Arousal Threshold and Apnea-Hypopnea Index. A Randomized, Double-Blind, Cross-Over Study.
abstract: Obstructive sleep apnea (OSA) has multiple pathophysiological causes. A low respiratory arousal threshold (ArTh) and a high loop gain (unstable ventilatory control) can contribute to recurrent respiratory events in patients with OSA. Prior studies have shown that donepezil, an acetylcholinesterase inhibitor, might improve OSA, but the mechanism is unknown.
  
  
  
  To determine whether a single dose of donepezil lowers the apnea-hypopnea index by modulating the ArTh or loop gain.
  
  
  
  In this randomized, double-blind, crossover trial, 41 subjects with OSA underwent two polysomnograms with ArTh and loop gain evaluated, during which 10 mg of donepezil or placebo was administered.
  
  
  
  Compared with placebo, sleep efficiency (77.2 vs. 71.9%; P = 0.015) and total sleep time decreased with donepezil (372 vs. 351 min; P = 0.004). No differences were found in apnea-hypopnea index (51.8 vs. 50.0 events/h; P = 0.576) or nadir oxygen saturation as determined by pulse oximetry (80.3 vs. 81.1%; P = 0.241) between placebo and donepezil, respectively. ArTh was not significantly changed (-18.9 vs. -18.0 cm H2O; P = 0.394) with donepezil. As a whole group, loop gain (ventilatory response to a 1-cycle/min disturbance) did not change significantly (P = 0.089).
  
  
  
  A single dose of donepezil did not appear to affect the overall severity of OSA in this patient group, and no consistent effects on ArTh or loop gain were observed. Donepezil may have minor effects on sleep architecture. Clinical trial registered with www.clinicaltrials.gov (NCT02264353).
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.|2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Owens
authors.affiliation: 3 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|4 Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, Alfred and Monash University, Melbourne, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Sands
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Orr
authors.affiliation: 5 Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil; and.
authors.forename: Walter
authors.initials: W
authors.lastname: Moraes
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Pamela
authors.initials: P
authors.lastname: DeYoung
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Erik
authors.initials: E
authors.lastname: Smales
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.|6 Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Jen
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
mesh_terms: D000328:Adult; D001143:Arousal / Q000187:drug effects*; D002140:California; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D018592:Cross-Over Studies; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010880:Piperidines / Q000008:administration & dosage*; D017286:Polysomnography; D012137:Respiratory System / Q000503:physiopathology*; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: arousal threshold; donepezil; loop gain; obstructive sleep apnea; treatment