Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial.
Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial.
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DOI：
10.1002/ana.24459
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发表时间：
2015-09
影响因子：
11.2
通讯作者：
Rye DB
中科院分区：
文献类型：
--
作者：
Trotti LM;Saini P;Bliwise DL;Freeman AA;Jenkins A;Rye DB
一些中枢性嗜睡综合征与脑脊液中GABA-A受体的阳性变构调节剂有关。据报道，GABA-A受体的负变构调节剂（包括克拉霉素）可减少这些患者的嗜睡。我们试图系统地评估克拉霉素对客观警觉性和主观嗜睡的影响。这是一项在嗜睡综合征（不包括发作性睡病伴卡他汀）和有脑脊液GABA-A受体异常增强证据的患者中进行的克拉霉素500 mg与早餐和午餐同服的5周、随机、安慰剂对照、双盲、交叉试验。这项研究是在一所大学附属的医学中心进行的。主要结果测量是每种情况下第2周时心理警戒任务（PVT）的中位反应时间。次要结局包括埃普沃思嗜睡量表、斯坦福大学嗜睡量表、睡眠功能结局、匹兹堡睡眠质量指数、SF-36和其他PVT指标。23名患者开始接受治疗。3名患者退出，对20例完整病例进行了最终分析。克拉霉素和安慰剂之间的中位反应时间无显著差异。与安慰剂组相比，克拉霉素组嗜睡的主观指标显著改善。味觉发生改变，但这是克拉霉素比安慰剂更常见的唯一副作用。未发生严重不良事件。克拉霉素治疗两周后，主观嗜睡改善，但精神警觉性没有改善。尽管还需要进一步的研究，但这表明克拉霉素可能是治疗难治性嗜睡患者的合理治疗选择。该试验在clinicaltrials.gov（NCT 01146600）上注册，并得到美国睡眠医学基金会的支持。
Some central hypersomnolence syndromes are associated with a positive allosteric modulator of GABA-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness. This was a five-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500 mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep, Pittsburgh Sleep Quality Index, the SF-36, and additional PVT measures. Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on twenty complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred. Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence. This trial was registered at clinicaltrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation.