Excessive Sleepiness Associated with Obstructive Sleep Apnea
Excessive Sleepiness Associated with Obstructive Sleep Apnea
Obstructive Sleep Apnea and Excessive Sleepiness
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by episodes of complete or partial upper airway obstruction during sleep. Many symptoms are associated with OSA, including excessive sleepiness.1 Approximately 75% of patients in sleep laboratory populations with excessive sleepiness have a sleep-related breathing disorder, of which OSA is the most prevalent form.2 Another analysis estimates that around 80% of OSA patients complain of both excessive sleepiness and cognitive performance impairment.3 In addition to its relationship with impaired cognitive function, excessive sleepiness has been shown to be associated with impairments in physical and social functioning, emotional state, and mental health.4 Excessive sleepiness has been shown to be associated with fatigue, reduced energy levels, and a diminished sense of wellbeing.5–7
Treatment Options
Behavioral changes, specifically weight loss, a reduction in alcohol
consumption, and the cessation of cigarette smoking, can all significantly
reduce the symptoms of OSA, and represent an important foundation of treatment. These recommendations are generally appropriate for all patients with OSA, but may be of significant value to those with mild OSA, as they may preclude more aggressive treatment approaches. However, in most cases recommendations for behavioral modifications are combined with nasal continuous positive airway pressure (nCPAP), which is considered to be the first-line therapy for moderate to severe OSA. The efficacy of nCPAP is well established, but compliance can be problematic for some patients. More recently, oral appliances that improve the patency of the upper airway by reinforcing its stability have become treatment options. Finally, surgical interventions for OSA, including uvulopalatopharyngoplasty (UPPP), laser-assisted uvulopalatopharyngoplast (LAUP), maxillo-mandibular advancement, and bariatric surgery, may all be considered, but tend to be most appropriate for patients who are unable or unwilling to comply with medical management of the condition.
Drug treatments for OSA have been considered and are currently in development. For example, BGC20–0166, a proprietary combination of two marketed serotonergic modulating drugs, is being tested in OSA patients to determine its efficacy in reducing the apnea–hypopnea index (AHI).8 The mechanism of this effect is believed to be related to increases in upper airway muscle tone and respiratory drive. Studies of BGC20–0166 in a rat model of sleep apnea indicate that it reduces the AHI by 90%. More recently, a 28-day double-blind, parallel-group, placebocontrolled polysomnographic study of BGC20–0166 in patients with sleep apnea revealed that it resulted in a 40% reduction in the mean AHI, relative to placebo, after 28 days of treatment. Oximetry revealed a trend in oxygen saturation that was consistent with the reduction in AHI, with no notable differences in the number of subjects with adverse events in the placebo and active drug treatment groups. These findings suggest that promising new therapeutics for sleep apnea are in development. However, as yet there is no drug treatment specifically indicated for OSA.
Unfortunately, despite the best efforts of the practitioner and patient, even with adequate use of nCPAP daytime sleepiness can persist.9–12 Modafinil, a wakefulness-promoting agent, was one of the first compounds to be evaluated for its ability to improve wakefulness in patients with excessive sleepiness associated with several sleep disorders, including OSA.10,13,14 According to a recent search of the National Institutes of Health (NIH) website, a small number of trials of other drugs have been conducted in recent years. One trial compared modafinil with xyrem and zolpidem, another evaluated pantoprazole in patients with OSA and comorbid acid reflux, and two others evaluated mometasone furoate nasal spray in patients with OSA associated with perennial allergic rhinitis.
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