Sullivan Shannon S, Guilleminault Christian
a Division of Sleep Medicine , Stanford University School of Medicine , 450 Broadway MC 5704, Redwood City , CA 94063 , USA.
Expert Opin Emerg Drugs. 2015;20(4):571-82. doi: 10.1517/14728214.2015.1115480. Epub 2015 Nov 24.
Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms.
This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA).
Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges.
阻塞性睡眠呼吸暂停（OSA）和发作性睡病是常见且症状负担重的睡眠障碍，包括明显的嗜睡、日间功能障碍和夜间睡眠不佳。两者都有不良健康后果的高风险。目前的治疗方法常常未得到充分利用，操作繁琐，成本高昂或伴有残留症状。
本综述涵盖了OSA和发作性睡病目前可用的治疗方法，讨论了潜在药物开发领域以及处于治疗研发阶段的药物，包括大麻素屈大麻酚（用于OSA）、组胺反向激动剂/拮抗剂匹托品（用于发作性睡病），以及具有不确定和/或多种活性的兴奋剂，如JZP-110和JZP-386（用于发作性睡病，可能也用于OSA）。最后，它探讨了目前市场上疗法的新方法和新用途，如碳酸酐酶抑制剂乙酰唑胺（用于OSA）。
OSA和发作性睡病都是需要终身治疗的嗜睡病症。在OSA方面，虽然在可预见的未来持续气道正压通气可能仍将是金标准疗法，但将OSA的表型和变异纳入治疗策略以实现更好、更个性化的疾病改善仍有很大空间。在发作性睡病方面，与OSA不同，药物治疗是目前的主要治疗手段。利用新机制治疗诸如嗜睡等靶向症状或能治疗发作性睡病多种症状的新型药物取得的进展带来了希望。然而，成本、便利性和副作用仍然是挑战。
