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Sleep Apnea
Excessive Sleepiness Associated with Obstructive Sleep Apnea
a report by
Gary Zammit, PhD
President and CEO, Clinilabs, Inc., and Clinical Associate Professor, Columbia University College of Physicians and Surgeons
Obstructive Sleep Apnea and Excessive Sleepiness relative to placebo, after 28 days of treatment. Oximetry revealed a trend
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder in oxygen saturation that was consistent with the reduction in AHI, with
characterized by episodes of complete or partial upper airway no notable differences in the number of subjects with adverse events in
obstruction during sleep. Many symptoms are associated with OSA, the placebo and active drug treatment groups. These findings suggest that
including excessive sleepiness.
1
Approximately 75% of patients in sleep promising new therapeutics for sleep apnea are in development. However,
laboratory populations with excessive sleepiness have a sleep-related as yet there is no drug treatment specifically indicated for OSA.
breathing disorder, of which OSA is the most prevalent form.
2
Another
analysis estimates that around 80% of OSA patients complain of both Unfortunately, despite the best efforts of the practitioner and patient, even
excessive sleepiness and cognitive performance impairment.
3
In with adequate use of nCPAP daytime sleepiness can persist.
9–12
Modafinil,
addition to its relationship with impaired cognitive function, excessive a wakefulness-promoting agent, was one of the first compounds to be
sleepiness has been shown to be associated with impairments in evaluated for its ability to improve wakefulness in patients with excessive
physical and social functioning, emotional state, and mental health.
4
sleepiness associated with several sleep disorders, including OSA.
10,13,14
Excessive sleepiness has been shown to be associated with fatigue, According to a recent search of the National Institutes of Health (NIH)
reduced energy levels, and a diminished sense of wellbeing.
5–7
website, a small number of trials of other drugs have been conducted in
recent years. One trial compared modafinil with xyrem and zolpidem,
Treatment Options another evaluated pantoprazole in patients with OSA and comorbid acid
Behavioral changes, specifically weight loss, a reduction in alcohol reflux, and two others evaluated mometasone furoate nasal spray in
consumption, and the cessation of cigarette smoking, can all significantly patients with OSA associated with perennial allergic rhinitis.
reduce the symptoms of OSA, and represent an important foundation of
treatment. These recommendations are generally appropriate for all Armodafinil
patients with OSA, but may be of significant value to those with mild OSA, In recent years, armodafinil, an isomer of modafinil, has become the most
as they may preclude more aggressive treatment approaches. However, in promising new therapy for excessive sleepiness associated with OSA. It
most cases recommendations for behavioral modifications are combined was approved by the US Food and Drug Administration (FDA) in 2007 to
with nasal continuous positive airway pressure (nCPAP), which is considered improve wakefulness in patients with excessive sleepiness associated with
to be the first-line therapy for moderate to severe OSA. The efficacy of OSA, narcolepsy, or shift-work sleep disorder. Modafinil is a racemic
nCPAP is well established, but compliance can be problematic for some compound containing an equal amount of the R- and S-enantiomer.
15
R-
patients. More recently, oral appliances that improve the patency of the modafinil has a significantly longer half-life (10–14 versus three to four
upper airway by reinforcing its stability have become treatment options. hours)
16–18
and is eliminated three times more slowly than S-modafinil.
17
Finally, surgical interventions for OSA, including uvulopalatopharyngoplasty The differences seen in the metabolism of these compounds can result in
(UPPP), laser-assisted uvulopalatopharyngoplast (LAUP), maxillo-mandibular significant differences in the plasma concentrations of the two
advancement, and bariatric surgery, may all be considered, but tend to be enantiomers. Unsurprisingly, dosing with armodafinil (R-modafinil) has
most appropriate for patients who are unable or unwilling to comply with been shown to produce higher plasma concentrations later in the day than
medical management of the condition.
Gary Zammit, PhD, is President and CEO of Clinilabs,
Drug treatments for OSA have been considered and are currently in
Inc., and a Clinical Associate Professor of Psychology
development. For example, BGC20–0166, a proprietary combination of and Psychiatry at the Columbia University College of
two marketed serotonergic modulating drugs, is being tested in OSA
Physicians and Surgeons. Dr Zammit served as President of
Pharmasys International. He earned a PhD in clinical
patients to determine its efficacy in reducing the apnea–hypopnea index
psychology from the University of Toledo, where he won
(AHI).
8
The mechanism of this effect is believed to be related to increases the Turin Service Award and the Leckie Scholar Award.
in upper airway muscle tone and respiratory drive. Studies of
Dr Zammit completed an internship and fellowship in the
Department of Psychiatry at the New York Hospital–
BGC20–0166 in a rat model of sleep apnea indicate that it reduces the AHI
Cornell University Medical College, where he won the
by 90%. More recently, a 28-day double-blind, parallel-group, placebo- Alumni Award for Excellence.
controlled polysomnographic study of BGC20–0166 in patients with sleep
gzammit@clinilabs.com
apnea revealed that it resulted in a 40% reduction in the mean AHI,
© TOUCH BRIEFINGS 2008
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