Trazodone Increases the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea and a Low Arousal Threshold

Study Objectives: The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep. Design: Patients were studied on 4 separate nights according to a within-subjects cross-over design. Setting: Sleep physiology laboratory. Patients: Seven patients with OSA and a low respiratory arousal threshold. Interventions: In-laboratory polysomnograms were obtained at baseline and after 100 mg of trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit). Measurements and Results: Trazodone increased the respiratory arousal threshold by 32 +/- 6% (-11.5 +/- 1.4 versus -15.3 +/- 2.2 cmH(2)O, P < 0.01) but did not alter the apnea-hypopnea index (39 +/- 12 versus 39 +/- 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with trazodone. Conclusions: Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway anatomy in these patients.