儿童发作性睡病药物治疗及进展

doi:10.12372/jcp.2025.24e1345

Abstract

Abstract:

Narcolepsy is a rare neurological disorder characterized by excessive daytime sleepiness, cataplexy, disturbed night sleep, sleep paralysis and sleep hallucinations. It typically onsets during childhood or adolescence. The treatment is focused on ameliorating clinical symptoms, encompassing drug therapy to alleviate symptoms such as excessive daytime sleepiness and cataplexy. Despite the fact that orexin replacement therapy and orexin receptor agonists are in the research stage, the majority of drugs for narcolepsy used in children are off-label. Hence, more clinical studies are requisite to validate their safety and efficacy in children.

Key words: child, narcolepsy, pharmacologic treatment

CLC Number:

ZHANG Yixin, HONG Siqi. Pharmacologic and upcoming treatment of pediatric narcolepsy[J].Journal of Clinical Pediatrics, 2025, 43(6): 475-482.

Figures/Tables 1

Table 1

References 57

[1]	中华医学会神经病学分会睡眠障碍学组. 中国发作性睡病诊断与治疗指南(2022版)[J]. 中华神经科杂志, 2022, 55(5): 406-420.
	Chinese Society of Sleep Disorders. Chinese guidelines for diagnosis and treatment of Narcolepsy (2022)[J]. Zhonghua Shenjingke Zazhi, 2022, 55(5): 406-420.
[2]	American Academy of Sleep Medicine. International classification of sleep disorders third edition, text revision (ICSD-3-TR)[M]. Darien, IL: American Academy of Sleep Medicine, 2023.
[3]	Liblau RS, Latorre D, Kornum BR, et al. The immuno-pathogenesis of narcolepsy type 1[J]. Nat Rev Immunol, 2024, 24(1): 33-48.
[4]	Li S, Yang J. Pitolisant for treating patients with narcolepsy[J]. Expert Rev Clin Pharmacol, 2020, 13(2): 79-84.
[5]	Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial[J]. Lancet Neurol, 2017, 16(3): 200-207. doi: S1474-4422(16)30333-7 pmid: 28129985
[6]	Meskill GJ, Davis CW, Zarycranski D, et al. Clinical impact of pitolisant on excessive daytime sleepiness and cataplexy in adults with narcolepsy: an analysis of randomized placebo-controlled trials[J]. CNS Drugs, 2021, 36(1): 61-69. doi: 10.1007/s40263-021-00886-x pmid: 34935103
[7]	Dauvilliers Y, Arnulf I, Szakacs Z, et al. Long-term use of pitolisant to treat patients with narcolepsy: Harmony Ⅲ Study[J]. Sleep, 2019, 42(11): zsz174.
[8]	Dauvilliers Y, Lecendreux M, Lammers GJ, et al. Safety and efficacy of pitolisant in children aged 6 years or older with narcolepsy with or without cataplexy: a double-blind, randomised, placebo-controlled trial[J]. Lancet Neurol, 2023, 22(4): 303-311. doi: 10.1016/S1474-4422(23)00036-4 pmid: 36931805
[9]	Triller A, Pizza F, Lecendreux M, et al. Real-world treatment of pediatric narcolepsy with pitolisant: A retrospective, multicenter study[J]. Sleep Med, 2023, 103: 62-68. doi: 10.1016/j.sleep.2023.01.015 pmid: 36758348
[10]	Claudio L A B. European guideline and expert statements on the management of narcolepsy in adults and children[J]. Eur J Neurol, 2021, 28(9): 2815-2830.
[11]	Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline[J]. J Clin Sleep Med, 2021, 17(9): 1881-1893. doi: 10.5664/jcsm.9328 pmid: 34743789
[12]	Franceschini C, Pizza F, Cavalli F, et al. A practical guide to the pharmacological and behavioral therapy of narcolepsy[J]. Neurotherapeutics, 2021, 18(1): 6-19. doi: 10.1007/s13311-021-01051-4 pmid: 33886090
[13]	Steven TS. Neurobiological and immunogenetic aspects of narcolepsy: Implications for pharmacotherapy[J]. Sleep Med Rev, 2019, 43: 23-36. doi: S1087-0792(18)30030-3 pmid: 30503715
[14]	Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy[J]. Ann Neurol, 1998, 43(1): 88-97.
[15]	Harsh JR, Hayduk R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy[J]. Curr Med Res Opin, 2006, 22(4): 761-774. doi: 10.1185/030079906X100050 pmid: 16684437
[16]	Lecendreux M, Bruni O, Franco P, et al. Clinical experience suggests that modafinil is an effective and safe treatment for paediatric narcolepsy[J]. J Sleep Res, 2012, 21(4): 481-483. doi: 10.1111/j.1365-2869.2011.00991.x pmid: 22283810
[17]	Ivanenko A, Tauman R, Gozal D. Modafinil in the treatment of excessive daytime sleepiness in children[J]. Sleep Med, 2003, 4(6): 579-582. pmid: 14607353
[18]	Mamelak M. Sleep, narcolepsy, and sodium oxybate[J]. Curr Neuropharmacol, 2022, 20(2): 272-291.
[19]	Chen C, Jenkins J, Zomorodi K, et al. Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies[J]. Clin Transl Sci, 2021, 14(6): 2278-2287.
[20]	J B. Sodium oxybate improves excessive daytime sleepiness in narcolepsy[J]. Sleep, 2006, 29(7): 939-946. pmid: 16895262
[21]	Xyrem International Study G. Further evidence supporting the use of sodium oxybate for the treatment of cataplexy: a double-blind, placebo-controlled study in 228 patients[J]. Sleep Med, 2005, 6(5): 415-421. pmid: 16099718
[22]	Plazzi G, Ruoff C, Lecendreux M, et al. Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation[J]. Lancet Child Adolesc Health, 2018, 2(7): 483-494. doi: S2352-4642(18)30133-0 pmid: 30169321
[23]	Lecendreux M, Plazzi G, Dauvilliers Y, et al. Long-term safety and maintenance of efficacy of sodium oxybate in the treatment of narcolepsy with cataplexy in pediatric patients[J]. J Clin Sleep Med, 2022, 18(9): 2217-2227. doi: 10.5664/jcsm.10090 pmid: 35689598
[24]	Bogan RK, Thorpy MJ, Dauvilliers Y, et al. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy[J]. Sleep, 2021, 44(3): zsaa206.
[25]	Bogan RK, Foldvary-Schaefer N, Skowronski R, et al. Long-term safety and tolerability during a clinical trial and open-label extension of low-sodium oxybate in participants with narcolepsy with cataplexy[J]. CNS Drugs, 2023, 37(4): 323-335. doi: 10.1007/s40263-023-00992-y pmid: 36947322
[26]	Dauvilliers Y, Roth T, Bogan R, et al. Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial[J]. Sleep, 2023, 46(11): zsad152.
[27]	Kushida CA, Shapiro CM, Roth T, et al. Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy[J]. Sleep, 2022, 45(6): zsab200.
[28]	Zomorodi K, Chen D, Lee L, et al. A randomized, double‐blind, placebo‐ and positive‐controlled, 4‐period crossover study of the effects of solriamfetol on QTcF intervals in healthy participants[J]. Clin Pharmacol Drug Dev, 2020, 10(4): 404-413.
[29]	Thorpy MJ, Shapiro C, Mayer G, et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy[J]. Ann Neurol, 2019, 85(3): 359-370. doi: 10.1002/ana.25423 pmid: 30694576
[30]	Malhotra A, Shapiro C, Pepin JL, et al. Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea[J]. Sleep, 2020, 43(2): zsz220.
[31]	Winter Y, Mayer G, Kotterba S, et al. Solriamfetol real world experience study (SURWEY): Initiation, titration, safety, effectiveness, and experience during follow-up for patients with narcolepsy from Germany[J]. Sleep Med, 2023, 103: 138-143. doi: 10.1016/j.sleep.2023.01.022 pmid: 36796288
[32]	Shellenberg TP, Stoops WW, Lile JA, et al. An update on the clinical pharmacology of methylphenidate: therapeutic efficacy, abuse potential and future considerations[J]. Expert Rev Clin Pharmacol, 2020, 13(8): 825-833.
[33]	Merrill M. Mitler RS, Roza Hajdukovich, et al. Treatment of narcolepsy: objective studies on methylphenidate, pemoline, and protriptyline[J]. Sleep, 1986, 9(1): 260-264.
[34]	Thorpy MJ, Bogan RK. Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications[J]. Sleep Med, 2020, 68: 97-109. doi: S1389-9457(19)30309-0 pmid: 32032921
[35]	Beckmann D, Lowman KL, Nargiso J, et al. Substance-induced psychosis in youth[J]. Child Adolesc Psychiatr Clin N Am, 2020, 29(1): 131-143.
[36]	Man KKC, Häge A, Banaschewski T, et al. Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study[J]. Lancet Psychiatry, 2023, 10(5): 323-333.
[37]	Zhang X, Berridge MS, Apana SM, et al. Discontinuation of methylphenidate after long-term exposure in nonhuman primates[J]. Neurotoxicol Teratol, 2023, 97: 107173.
[38]	Jin L, Shi L, Zhang Y, et al. Antidepressants for the treatment of narcolepsy: a prospective study of 148 patients in northern China[J]. J Clin Neurosci, 2019, 63: 27-31. doi: S0967-5868(18)31376-6 pmid: 30837110
[39]	Ratkiewicz M, Splaingard M. Treatment of cataplexy in a three-year-old using venlafaxine[J]. J Clin Sleep Med, 2013, 09(12): 1341-1342.
[40]	Møller LRØ, John R. Treatment with venlafaxine in six cases of children with narcolepsy and with cataplexy and hypnagogic hallucinations[J]. J Child Adolesc Psychopharmacol, 2009, 19(2): 197-201.
[41]	Schachter M, Parkes JD. Fluvoxamine and clomipramine in the treatment of cataplexy[J]. J Neurol Neurosurg Psychiatry, 1980, 43(2): 171-174.
[42]	Larrosa O, de la Llave Y, Bario S, et al. Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study[J]. Sleep, 2001, 24(3): 282-285. pmid: 11322710
[43]	Frey J, Darbonne C. Fluoxetine suppresses human cataplexy: a pilot study[J]. Neurology, 1994, 44: 707-709. pmid: 8164831
[44]	Fonseca Hde A, Lopes DA, Pereira D, et al. The use of citalopram for the treatment of cataplexy[J]. Sleep Sci, 2014, 7(1): 50-52. doi: 10.1016/j.slsci.2014.07.016 pmid: 26483901
[45]	Huang YS, Guilleminault C. Narcolepsy: action of two γ-aminobutyric acid type B agonists, baclofen and sodium oxybate[J]. Pediatr Neurol, 2009, 41(1): 9-16.
[46]	Dhafar HO, BaHammam AS. Body weight and metabolic rate changes in narcolepsy: current knowledge and future directions[J]. Metabolites, 2022, 12(11): 1120.
[47]	Melzi S, Prevot V, Peyron C. Precocious puberty in narcolepsy type 1: Orexin loss and/or neuroinflammation, which is to blame?[J]. Sleep Med Rev, 2022, 65: 101683.
[48]	Valizadeh P, Momtazmanesh S, Plazzi G, et al. Connecting the dots: an updated review of the role of autoimmunity in narcolepsy and emerging immunotherapeutic approaches[J]. Sleep Med, 2024, 113: 378-396. doi: 10.1016/j.sleep.2023.12.005 pmid: 38128432
[49]	Lecendreux M, Berthier J, Corny J, et al. Intravenous immunoglobulin therapy in pediatric narcolepsy: a nonrandomized, open-label, controlled, longitudinal sbservational dtudy[J]. J Clin Sleep Med, 2017, 13(3): 441-453. doi: 10.5664/jcsm.6500 pmid: 28095967
[50]	Chen W, Black J, Call P, et al. Late-Onset narcolepsy presenting as rapidly progressing muscle weakness: response to plasmapheresis[J]. Ann Neurol, 2005, 58(3): 489-490. pmid: 16130098
[51]	Pincherle A, Villani F, Ferini Strambi L, et al. Immuno-adsorption for the treatment of narcolepsy with cataplexy[J]. Neurol Sci, 2008, 29(6): 499-500.
[52]	Weinhold SL, Seeck-Hirschner M, Nowak A, et al. The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy[J]. Behav Brain Res, 2014, 262: 8-13. doi: 10.1016/j.bbr.2013.12.045 pmid: 24406723
[53]	Ishikawa T, Hara H, Kawano A, et al. Danavorexton, a selective orexin 2 receptor agonist, provides a symptomatic improvement in a narcolepsy mouse model[J]. Pharmacol Biochem Behav, 2022, 220: 173464.
[54]	Evansa R, Kimura H, Alexander R, et al. Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients[J]. Proc Natl Acad Sci U S A, 2022, 119(35): e2207531119.
[55]	Yamada R, Narita N, Ishikawa T, et al. The orexin receptor 2 (OX2R)-selective agonist TAK-994 increases wakefulness without affecting cerebrospinal fluid orexin levels in cynomolgus monkeys[J]. Pharmacol Biochem Behav, 2024, 234: 173690.
[56]	Dauvilliers Y, Mignot E, del Río Villegas R, et al. Oral orexin receptor 2 agonist in narcolepsy type 1[J]. N Engl J Med, 2023, 389(4): 309-321.
[57]	Mitsukawa K, Terada M, Yamada R, et al. TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models[J]. Sci Rep, 2024, 14(1): 20838. doi: 10.1038/s41598-024-70594-1 pmid: 39242684

药物	作用机制	药代动力学	作用症状	用法用量	不良反应
替洛利生	H3受体拮抗剂/反向激动剂	T_max 3.5小时 T_1/2 20小时	EDS、猝倒、睡眠幻觉、睡眠瘫痪	口服，每天早上1次成人：9~36 mg·d^-1，起始剂量9 mg·d^-1 儿童（6岁及以上）：4.5~36 mg·d^-1，起始剂量4.5 mg·d^-1	失眠、头痛、恶心、焦虑、易怒、头晕、抑郁、震颤、睡眠障碍、疲劳、呕吐、眩晕、消化不良等
莫达非尼	多巴胺再摄取抑制剂	T_max 2小时 T_1/2 9~14小时	EDS	口服，每天早上1次成人：200~400 mg·d^-1，起始剂量100 mg·d^-1 儿童：无推荐	头痛、恶心、腹泻、失眠等，严重不良反应：Stevens-Johnson综合征、重症多形性红斑
羟丁酸钠	GABA-B受体激动剂	T_max 0.5~1.25小时 T_1/2 0.5~1小时	EDS、猝倒、睡眠幻觉、睡眠瘫痪、夜间睡眠紊乱	口服，每晚2次（睡前和半夜）成人：6~9 g/晚，起始剂量4.5 g/晚儿童（7岁及以上）：最大推荐剂量6~9 g/晚，起始剂量≤4.5 g/晚	遗尿、恶心、呕吐、头痛、体重减轻、食欲下降、鼻咽炎、头晕等，严重不良反应：急性精神症状、自杀意念，大剂量引起呼吸抑制
索安非妥	多巴胺和去甲肾上腺素再摄取抑制剂	T_max 2~3小时 T_1/2 7小时	EDS	口服，每天早上1次成人：75~150 mg·d^-1，起始剂量75 mg·d^-1 儿童：无推荐	头痛、食欲下降、失眠、恶心等
哌甲酯（缓释片）	多巴胺和去甲肾上腺素再摄取抑制剂	T_max 6~8小时 T_1/2 3.5小时	EDS	口服，每天早上1次成人：18~54 mg·d^-1，起始剂量18或36 mg·d^-1 儿童（6岁以上）：18~54 mg·d^-1，起始剂量18 mg·d^-1	失眠、紧张、头痛、食欲减退等，罕见不良反应：精神疾病，避免在患心脏病患者中使用

Pharmacologic and upcoming treatment of pediatric narcolepsy

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