Trazodone increases arousal threshold in obstructive sleep apnoea

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean +/- SD age 49 +/- 9yrs, apnoea/hypopnoea index 52 +/- 32 events h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO2 and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CPO2 tension (PET,CO2) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher PET,CO2 level (mean +/- SD 7.30 +/- 0.57 versus 6.62 +/- 0.64 kPa (54.9 +/- 4.3 versus 49.8 +/- 4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO2 level, the maximal oesophageal pressure swing was greater (19.4 +/- 4.0 versus 13.1 +/- 4.9 cmH(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1 +/- 4.7 versus -0.38 +/- 4.2 cmH(2)O with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO2 levels.