Clinical Review

Treatments for Obstructive Sleep Apnea


 

References

2). Via inspiration detected through the sensory leads, the neurostimulator uses an algorithm to predict the onset of inspiration. The neurostimulator delivers electric pulses to the hypoglossal nerve between the end of expiration and the beginning of the next expiratory phase, thus activating and protruding the genioglossus muscle and counteracting the negative pressures and collapsing forces on the upper airways during inspiration [87–93]. After implantation, device titration occurs by gradually adjusting stimulus pulse intensity, frequency, and width to levels that are tolerable to the OSA patient and that lead to significant decreases in AHI [87–93].

In all trials to date, there were significant decreases in AHI as long as 3 years post implantation [87–93]. There were significant improvements in symptoms of sleepiness, mood, quality of life, and sleep quality [87,88,90–94]. When OSA patients had their neurostimulators turned off for 5 days to a week, AHI returned back to baseline levels [89,92]. However, all the trials excluded morbidly obese individuals [87–93] because investigations showed that HNS had no therapeutic effect with elevated BMI [88,90]. The drawbacks of HNS are that it is surgically invasive and minor adverse events have been reported: procedural-related events (eg, numbness/pain/swelling/infection at incision site, temporary tongue weakness) that resolved with time, pain medication, and/or antibiotic treatment, or therapy-related events (eg, tongue abrasions cause by tongue movement over teeth, discomfort associated with stimulation) that resolved after acclimation. Serious adverse events occurred infrequently, such as infection at incision site requiring device removal or subsequent surgery to reposition or replace electrode cuff or malfunctioning neurostimulator [87,88,90]. HNS durability at 18 and 36 months was still very effective, with decreased AHI and increase quality of life and sleep being sustained; adverse events were uncommon this long after implantation [91,93]. Although surgery is required and adverse events are reported, the long-term significant improvement of OSA makes this a very viable treatment option over CPAP. However, increasing prevalence rates of OSA are correlated to increasing obesity rates [2], which may limit the usefulness of HNS since a BMI of more than 40 might preclude individuals to this treatment.

Pharmacologic Treatment

There are no approved pharmacologic treatments for OSA. A recent Cochrane review and meta-analysis assessed clinical trials of various drugs treating OSA. These drugs targeted 5 strategies at alleviating OSA: increasing ventilatory drive (progestogens, theophylline, and acetazolamide), increasing upper airway tone (serotonergics and cholinergics), decreasing rapid eye movement sleep (antidepressants and clonidine), increasing arousal threshold (eszopiclone), and/or increasing the cross-sectional area or reducing the surface tension of the upper airway through topical therapy (fluticasone and lubricant). The review concluded that “some of the drugs may be helpful; however, their tolerability needs to be considered in long-term trials.” Some of these drugs had little or no effect on AHI, and if they did have an effect on AHI, side effects outweighed the benefit [95]. Since then, more investigations of other drugs targeted at the previously aforementioned strategies or via new strategies have been published.

Dronabinol (synthetic Δ 9-THC), a nonselective cannabinoid type 1 and type 2 receptor agonist, significantly reduced AHI and improved subjective sleepiness and alertness in a single-blind dose-escalation (2.5, 5, or 10 mg) proof-of-concept study [96,97]. Dronabinol most likely increases upper airway tone though inhibition of vagal afferents [98,99]. There were no serious adverse events associated with dronabinol. Minor adverse events included somnolence and increased appetite. Increased appetite might lead to increased weight and contradict any beneficial effects of dronabinol; however, in the 3-week treatment period no weight gain was observed [97]. This might have been due to drug administration occurring before going to sleep with no opportunity to eat. A larger randomized controlled study will be needed to establish the safety and efficacy of dronabinol.

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