The Effect of Donepezil on Arousal Threshold and Apnea-Hypopnea Index A Randomized, Double-Blind, Cross-Over Study
Owens, Robert L.
Moraes, Walter [UNIFESP]
Is part ofAnnals Of The American Thoracic Society
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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 minP = 0.004). No differences were found in apnea-hypopnea index (51.8 vs. 50.0 events/hP = 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 H2OP = 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.
CitationAnnals Of The American Thoracic Society. New York, v. 13, n. 11, p. 2012-2018, 2016.
SponsorshipNational Institutes of Health (NIH)
National Natural Science Foundation of China
National Health and Medical Research Council of Australia Early Career Fellowship
R.G. Menzies award
American Heart Association
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