The Effects of Trazodone on Sleep Apnea Severity
The Effects of Trazodone on Sleep Apnea Severity
In Obstructive sleep apnea (OSA), the upper airway closes over and over again during sleep.
 This leads to disrupted sleep (waking up during the night), daytime sleepiness, and an
 increased risk for developing high blood pressure. Currently, the best treatment for
 obstructive sleep apnea is sleeping with a mask that continuously blows air into the nose
 (i.e. Continuous positive airway pressure [CPAP] treatment). While CPAP treatment stops the
 upper airway from closing in most people, many people have difficulty sleeping with the mask
 in place and therefore do not use the CPAP treatment. This research study is being conducted
 to learn whether using a sedative will improve OSA severity by altering some of the traits
 that are responsible for the disorder.
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.
Inclusion Criteria for OSA Patients:

 -  OSA (elevated AHI).

 -  Age range 18-70 years.

 Exclusion Criteria:

 -  Any known cardiac (apart from treated hypertension), pulmonary (including asthma),
 renal, neurologic (including epilepsy), neuromuscular, or hepatic disease.

 -  Susceptible to stomach ulcers.

 -  Pregnant women.

 -  History of hypersensitivity to Afrin, Lidocaine, trazodone and/or donepezil.

 -  History of bleeding diathesis and/or gastrointestinal bleeding.

 -  Use of any medications that may affect sleep or breathing.

 -  A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar
 disorder, major depression, panic or anxiety disorders.

 -  Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs.

 -  More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

 -  Desaturations to below 70% lasting greater than 10 seconds in duration per event on
 polysomnography.