title: Trazodone increases arousal threshold in obstructive sleep apnoea.
abstract: 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 CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) 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 CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(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 CO(2) levels.
authors.affiliation: Sleep Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. rheinzer@post.harvard.edu
authors.forename: R C
authors.initials: RC
authors.lastname: Heinzer
authors.forename: D P
authors.initials: DP
authors.lastname: White
authors.forename: A S
authors.initials: AS
authors.lastname: Jordan
authors.forename: Y L
authors.initials: YL
authors.lastname: Lo
authors.forename: L
authors.initials: L
authors.lastname: Dover
authors.forename: K
authors.initials: K
authors.lastname: Stevenson
authors.forename: A
authors.initials: A
authors.lastname: Malhotra
mesh_terms: D000328:Adult; D001143:Arousal / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D014196:Trazodone / Q000627:therapeutic use*
chemical_list: D014196:Trazodone