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Trazodone increases arousal threshold in obstructive sleep apnoea

¹ Sleep Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, ² Service de Pneumologie et Centre d'Investigation et de Recherche sur le Sommeil (CIRS), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, and ³ Dept of Thoracic Medicine, Chang Gang Memorial Hospital, Taipei, Taiwan.

CORRESPONDENCE: R. C. Heinzer, Service de Pneumologie, Centre d'investigation et de Recherche sur le Sommeil (CIRS), Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. Fax: 41 213146752. E-mail: rheinzer{at}post.harvard.edu

Keywords: Arousal threshold, carbon dioxide, oesophageal pressure, sleep-disordered breathing, trazodone

Received: June 5, 2007
Accepted January 22, 2008

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±9 yrs, 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 CO₂ tension (P_ET,CO2) was monitored with a nasal catheter.

During trazodone nights, compared with placebo nights, the arousals occurred at a higher P_ET,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 cmH₂O) and the oesophageal pressure nadir before the arousals was lower (-5.1±4.7 versus -0.38±4.2 cmH₂O) 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.