The Effects of Trazodone on the Severity of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular morbidity and mortality, making OSA a major health concern. Current evidence suggests that OSA pathogenesis involves the interactions of at least four physiological traits comprising: 1) the pharyngeal anatomy and its propensity towards collapse. This collapsibility of the upper airway is measured as the critical closing pressure or PCRIT. 2) the ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation) measured as the increase in upper airway electromyography (EMG) activity above the baseline level. 3) the arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep) measured as the epiglottic pressure occurring just at the time of arousal and 4) the stability of the ventilatory feedback loop (i.e. loop gain). Continuous positive airway pressure (CPAP) is the most common treatment for OSA but it is often poorly tolerated; only ~50% of patients diagnosed with OSA continue therapy beyond 3 months. Given this limitation, alternative approaches have been tested and have generally focused on the use of oral appliances and upper airway surgery. In addition to these alternative therapies, the use of pharmacological agents for the treatment of OSA has been gaining widespread interest. Previous data have shown that the non-myorelaxant hypnotic trazodone increases the arousal threshold however its effects on sleep apnea severity remain unclear. Based on studies showing that increasing the arousal threshold with a different hypnotic improves sleep apnea severity, we hypothesize that trazodone will increase the arousal threshold and this will be associated with an improvement in sleep apnea severity. Therefore the overall aim of this study is to examine the effects that trazodone has on OSA severity. STUDY DESIGN: A double-blinded randomized control design will be used. Initially, participants will be randomized to the trazodone or placebo arm where they will have both a clinical polysomnography (PSG) with the addition of an epiglottic pressure cathether. The purpose of the clinical PSG is to determine the severity of OSA (i.e. AHI) and the epiglottic catheter allows the calculation of the arousal threshold to be completed. During the trazodone arm, participants will be given trazodone (100mg by mouth) to take before bed. During the placebo arm, subjects will be given a placebo to take before bed. Participants will have at least a 1-week washout period before cross over to the next arm of the study whereby the clinical PSG will be repeated. In total each subject will be studied for 2 nights.