The Effects of Trazodone on Sleep Apnea Severity
| Status: | Completed |
|---|---|
| Conditions: | Insomnia Sleep Studies, Pulmonary |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | March 2013 |
| End Date: | December 2014 |
| Contact: | Andrew Wellman, MD, PhD |
| Email: | awellman@rics.bwh.harvard.edu |
| Phone: | 6177328483 |
The Effects of Trazodone on the Severity of Obstructive Sleep Apnea
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.
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.
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.
We found this trial at
1
site
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
Click here to add this to my saved trials
