The Effect of Donepezil on Arousal Threshold and Apnea Hypopnea Index: A Randomized, Double-blind Cross-over Study.
Ann Am Thorac Soc. 2016 Jul 21;
Authors: Li Y, Owens RL, Sands S, Orr J, Moraes W, DeYoung P, Smales E, Jen R, Malhotra A
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 small 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 (AHI) by modulating the ArTh or loop gain.
METHODS: In this randomized, double-blind cross-over trial, Forty-one OSA subjects underwent two polysomnograms with ArTh and loop gain evaluated, during which 10 mg of donepezil or placebo were administered.
MEASUREMENTS AND MAIN RESULTS: Compared to placebo, sleep efficiency (77.2 vs 71.9%; P=0.015) and total sleep time decreased with donepezil (372 vs 351min; P=0.004). No differences were found in AHI (51.8 vs 50.0 events/hr; P=0.576), or nadir SpO2 (80.3 vs 81.1%; P=0.241) between placebo and donepezil, respectively. ArTh was not significantly changed (-18.9 vs -18.0 cmH2O; P=0.394) with donepezil. As a whole group, loop gain (LG1, ventilatory response to a 1 cycle/min disturbance) did not change significantly (P=0.089).
CONCLUSIONS: A single dose of donepezil does 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 clinicaltrials.gov (NCT02264353).
PMID: 27442715 [PubMed - as supplied by publisher]
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