Trazodone Increases Arousal Threshold in Obstructive Sleep Apnea

A low arousal threshold is believed to predispose to breathing instability during sleep. We hypothesized that trazodone, a non-myorelaxant sleep promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnea (OSA) patients. Nine OSA patients (age 49±9 yr AHI 52±32 events/h) were studied on two nights, one with trazodone 100mg and one with a placebo, in a double blind randomized fashion. While on CPAP, repeated arousals were induced: 1) by increasing inspired CO2 and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an esophageal balloon. End tidal CO2 (EtCO2) was monitored with a nasal catheter. During trazodone nights compared with placebo nights, the arousals occurred at a higher EtCO2 level (mean±sd): 54.9±4.3 vs 49.8±4.8 mmHg (p=0.038). When arousals were triggered by increasing inspired CO2 level, the maximal esophageal pressure swing was greater: 19.4±4.0 vs 13.1±4.9 cmH2O (p=0.002) and the esophageal pressure nadir before the arousals was lower: -5.1±4.7 vs-0.38±4.2 cmH2O (p=0.02) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal esophageal pressure swings before the arousals were not different. Trazodone 100mg increases the effort-related arousal threshold in response to hypercapnia in OSA patients and allows them to tolerate higher CO2 levels.