Abstract

Copyright © 2015 by the American Thoracic Society. Rationale: A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA. Objectives: We aimed to examine how trazodone alters OSA severity and arousal threshold. We hypothesized that trazodone would increase the arousal threshold and improve the apnea/hypopnea index in selected patients with OSA. Methods: Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving trazodone and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly. Measurements and Main Results: Compared with placebo, trazodone resulted in a significant reduction in AHI, without worsening oxygen saturation or respiratory event duration. Trazodone was not associated with a significant change in the non-REM arousal threshold compared with placebo. In subgroup analysis, responders to trazodone spent less time in N1 sleep and had an accompanying reduction in arousal index, whereas nonresponders were not observed to have a change in sleep parameters. Conclusions: These findings suggest that trazodone could be effective therapy for patients with OSA without worsening hypoxemia. Future studies should focus on underlying mechanisms and combination therapies to eliminate OSA.