Leu-Semenescu Smaranda, Nittur Nandy, Golmard Jean-Louis, Arnulf Isabelle
National Reference Centre for Narcolepsy and Idiopathic Hypersomnia, France; AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Service des Pathologies du Sommeil, Paris, France; Pierre and Marie Curie University, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Inserm U 1127, CNRS UMR7225, Paris, France.
AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Service des Pathologies du Sommeil, Paris, France.
Sleep Med. 2014 Jun;15(6):681-7. doi: 10.1016/j.sleep.2014.01.021. Epub 2014 Mar 18.
To evaluate the benefits and risks of pitolisant (a wake-enhancing drug that increases the histamine release in the brain by blocking presynaptic H3 histamine reuptake) in patients with idiopathic (IH) and symptomatic (SH) hypersomnia plus sleepiness refractory to available stimulants (modafinil, methylphenidate, mazindol, sodium oxybate, and d-amphetamine).
Through retrospective analyses of patient files, the benefit (the score from the Epworth Sleepiness Scale [ESS], authorization renewal) and tolerance (side-effects) of pitolisant were assessed.
A total of 78 patients with IH (n=65%, 78% women) and SH (n=13%, 54% women) received pitolisant 5-50 mg once per day over the course of five days to 37 months. The median (interquartile range) ESS scores of patients with IH decreased from 17 (15.5-18.5) to 14 (12-17). There were 36% responders (ESS fall of > or =3). The improvement in ESS score (-1.9±2.6) was different from 0 in IH without long sleep time (P<0.002) and in IH with a long sleep time (P<0.0001), but not in SH. Forty-four (63%) patients with IH and 12 (77%) patients with SH stopped pitolisant, mostly due to a lack of efficacy. Side-effects included gastrointestinal pain (15.4%), increased appetite and weight gain (14.1%), headache (12.8%), insomnia (11.5%), and anxiety (9%), as well as exceptional reports of depression and persistent genital arousal.
Pitolisant had a long-term favorable benefit/risk ratio in 23-38% of drug-resistant patients with IH and SH, suggesting that histamine neurons can be stimulated in severe idiopathic and symptomatic hypersomnia.
评估匹托利生（一种促醒药物，通过阻断突触前H3组胺再摄取增加大脑中的组胺释放）对患有特发性（IH）和症状性（SH）发作性睡病且对现有兴奋剂（莫达非尼、哌甲酯、吗茚酮、羟丁酸钠和d - 苯丙胺）难治性嗜睡患者的益处和风险。
通过对患者病历的回顾性分析，评估匹托利生的益处（爱泼沃斯思睡量表[ESS]评分、授权续签）和耐受性（副作用）。
共有78例IH患者（n = 65%，女性占78%）和SH患者（n = 13%，女性占54%）在5天至37个月的时间里每天接受一次5 - 50 mg的匹托利生治疗。IH患者的ESS评分中位数（四分位间距）从17（15.5 - 18.5）降至14（12 - 17）。有36%的患者有反应（ESS下降≥3分）。在无长睡眠时间的IH患者（P < 0.002）和有长睡眠时间的IH患者（P < 0.0001）中，ESS评分的改善（-1.9±2.6）与0不同，但在SH患者中并非如此。44例（63%）IH患者和12例（77%）SH患者停用了匹托利生，主要原因是缺乏疗效。副作用包括胃肠道疼痛（15.4%）、食欲增加和体重增加（14.1%）、头痛（12.8%）、失眠（11.5%）和焦虑（9%），以及关于抑郁和持续性性唤起的特殊报告。
匹托利生在23% - 38%的耐药性IH和SH患者中具有长期良好的效益/风险比，这表明在严重的特发性和症状性发作性睡病中可以刺激组胺能神经元。
