Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness
Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness
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DOI：
10.1097/wnf.0b013e318246879d
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发表时间：
2012-03
影响因子：
1
通讯作者：
C. Inocente;I. Arnulf;H. Bastuji;A. Thibault-Stoll;A. Raoux;R. Reimão;Jian-Sheng Lin;P. Franco
中科院分区：
文献类型：
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作者：
C. Inocente;I. Arnulf;H. Bastuji;A. Thibault-Stoll;A. Raoux;R. Reimão;Jian-Sheng Lin;P. Franco
目的：嗜睡症是一种罕见的致残性睡眠障碍，其特征是白天过度嗜睡和猝厥（肌肉张力突然丧失）。阻断组胺H3自身受体的药物，如pitolisant，构成了一类新发现的兴奋剂，因为它们能增加脑组胺，增强动物和成人嗜睡症患者的清醒状态。方法：我们报告了4例青少年发作性睡病/猝厥伴严重白天嗜睡，现有治疗（莫达非尼、哌醋甲酯、马辛多尔、氧酸钠和d -安非他明）难治性的超说明书使用匹托利坦的经验。结果所有青少年均在儿童期发病（11.3±2.4岁，男生占50%），接受抗压治疗时年龄为17.3±0.8岁。抗压剂从10 mg增加到30 mg （n = 1）和40 mg （n = 3）。单用匹立松时Epworth困倦评分从14.3±1.1降至9.5±2.9 (P = 0.03)，联用马辛多尔（n = 1）、哌醋甲酯（n = 1）或氧酸钠加莫达非尼（n = 1）时Epworth困倦评分为7±3.4。醒觉维持试验的平均睡眠发作潜伏期由31±14分钟增加到36±8分钟（P = 0.21）。中风的严重程度和发作频率均略有改善。不良反应轻微（失眠、头痛、潮热、腿痛和幻觉）且短暂，2例青少年持续失眠。这种益处在平均13个月后保持不变。结论spitolisant是治疗青少年发作性睡病患者难治性嗜睡的一种可接受的治疗方法。
ObjectiveNarcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult narcolepsy. MethodsWe report our experience with the off-label use of pitolisant in 4 teenagers with narcolepsy/cataplexy with severe daytime sleepiness, refractory to available treatments (modafinil, methylphenidate, mazindol, sodium oxybate, and D-amphetamine). ResultsAll teenagers developed their disease during childhood (11.3 ± 2.4 years; 50% boys) and were 17.3 ± 0.8 years old at the time of pitolisant therapy. Pitolisant treatment was increased from 10 to 30 mg (n = 1) and 40 mg (n = 3). The adapted Epworth Sleepiness Score decreased from 14.3 ± 1.1 to 9.5 ± 2.9 (P = 0.03) with pitolisant alone to 7 ± 3.4 when combined with mazindol (n = 1), methylphenidate (n = 1), or sodium oxybate plus modafinil (n = 1). Mean sleep onset latency increased from 31 ± 14 minutes to 36 ± 8 minutes (P = 0.21) on the maintenance of wakefulness test. The severity and frequency of cataplexy were slightly improved. Adverse effects were minor (insomnia, headache, hot flushes, leg pain, and hallucinations) and transitory, except for insomnia, which persisted in 2 teenagers. The benefit was maintained after a mean of 13 months. ConclusionsPitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy.