Treatments for Obstructive Sleep Apnea

The sedative zopiclone was used to increase arousal threshold without effecting genioglossus activity [100]. Eszopiclone, a drug in the same class, has been used in the past with unfavorable results [95]. Zopiclone was used in a small double-blind randomized controlled cross-over study. Zopiclone significantly increased respiratory arousal threshold without effecting genioglossus activity or the upper airway’s response to negative pressure. Thus, there was a trend in the zopiclone treatment to increase sleep efficiency. However, zopiclone had no effect on AHI, and increased oxygen desaturation [100]. Similar to eszopiclone, the results for zopiclone are not promising.

A new strategy to treat OSA is to modify pharmacologically “loop gain,” a dimensionless value quantifying the stability of the ventilatory control system. A high loop gain signifies instability in the ventilatory control system and predisposes an OSA person to recurrent apneas [101–103]. Three studies used drugs that inhibit carbonic anhydrase to stabilize the ventilatory control system [104–106]. Two studies used acetazolamide, which decreased loop gain in OSA patients [104,105]. Acetazolamide only decreased AHI in non–rapid eye movement (NREM) sleep, and there was a slight correlation between decrease in loop gain and total AHI [105]. Acetazolamide also decreased ventilatory response to spontaneous arousal, thus promoting ventilatory stability [104]. In the last study, zonisamide, a carbonic anhydrase inhibitor that also causes weight loss, was investigated in OSA patients. Sleep apnea alleviation, measured in terms of absolute elimination of sleep apnea by mechanical or pharmacologic treatment, was 61% and 13% for CPAP and zonisamide, respectively, compared with placebo. In other words, zonisamide decreased AHI but not to the extent of CPAP [106]. Zonisamide also decreased arousals and marginally, but significantly, decreased weight compared to the CPAP group. Although carbonic anhydrase inhibitors have promise as an alternative treatment, long-term use is poorly tolerated [101] and further studies need to be completed.

OSA has been linked with gastroesophageal reflux disease (GERD), with studies suggesting OSA precipitates GERD [107] or GERD precipitates OSA [108]. A meta-analysis was recently published looking at studies that used proton pump inhibitors (PPI) to treat GERD and the effects it would have on OSA [109]. The meta-analysis only included 2 randomized trials and 4 prospective cohort studies. Two of the cohort studies showed a significant decrease, and one cohort showed no difference in apnea indices; and all 4 of the cohort studies showed no difference in AHI. In one trial, the frequency of apnea attacks as recorded by diaries significantly decreased. In 3 cohort studies and one trial, symptoms of sleepiness significantly decreased [109]. A study that was not included in the meta-analysis showed that 3 months of PPI treatment decreased AHI but did not alter sleep efficiency [110]. Larger randomized controlled studies need to be conducted on the effects of PPIs on OSA, especially since PPIs are well tolerated with only weak observational associations between PPI therapy and fractures, pneumonia, mortality, and nutritional deficiencies [111].

The drugs mentioned above have potential for treating OSA in patients intolerant to CPAP. The efficacy and side effects of the drugs will need to be studied for long-term use. However, development of pharmacologic treatments has been hampered by incomplete knowledge of the relevant sleep-dependent peripheral and central neural mechanisms controlling ventilatory drive and upper airway muscles. More importantly, additional basic science research needs to focus on the neurobiological and neurophysiological mechanisms underlying OSA to develop new pharmacotherapies or treatment strategies, or to modify previous treatment strategies.