Yanru Li1,2, Robert L Owens2, Scott Sands3,4, Jeremy Orr2, Walter Moraes5, Pamela DeYoung2, Erik Smales2, Rachel Jen2,6, Atul Malhotra2. 1. 1 Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. 2. 2 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California. 3. 3 Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 4. 4 Department of Allergy, Immunology and Respiratory Medicine and Central Clinical School, Alfred and Monash University, Melbourne, Australia. 5. 5 Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil; and. 6. 6 Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
RATIONALE: 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. OBJECTIVES: To determine whether a single dose of donepezil lowers the apnea-hypopnea index by modulating the ArTh or loop gain. METHODS: In this randomized, double-blind, crossover trial, 41 subjects with OSA underwent two polysomnograms with ArTh and loop gain evaluated, during which 10 mg ofdonepezil or placebo was administered. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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).
RCT Entities:
RATIONALE: 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. OBJECTIVES: To determine whether a single dose of donepezil lowers the apnea-hypopnea index by modulating the ArTh or loop gain. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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).
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