Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2024-11-01 Epub Date: 2024-09-21 DOI:10.1007/s40263-024-01122-y

Lynn Marie Trotti, Tyler Blake, Romy Hoque, David B Rye, Surina Sharma, Donald L Bliwise

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引用次数: 0

Abstract

Background and objective: Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders.

Methods: Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups.

Results: Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine.

Conclusion: Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2.

Registration: Clinicaltrials.gov Registration (NCT03772314) 12/10/18. .

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莫达非尼与安非他明-去甲安非他明治疗特发性失眠症和 2 型嗜睡症：随机、盲法、非劣效试验。

背景和目的：尽管目前有多种治疗 2 型嗜睡症和特发性嗜睡症的方法，但仍需要对苯丙胺类药物、嗜睡以外的症状和比较效果进行评估。我们对莫达非尼与苯丙胺-右旋苯丙胺治疗这些疾病进行了随机、全盲、非劣效试验：44名成人被随机分配到莫达非尼或苯丙胺-右旋苯丙胺中，分别滴定到最大莫达非尼200毫克，每天两次或苯丙胺-右旋苯丙胺20毫克，每天两次，为期12周。主要结果是埃普沃思从基线到第12周的变化，非劣效性阈值为2点。次要结果为：(1) 患者对疾病严重程度、嗜睡、睡眠惰性和认知能力变化的总体印象；(2) 失眠严重程度指数从基线到第 12 周的变化；(3) 睡眠惰性问卷从基线到第 12 周的变化。对各组的不良事件进行比较：结果：莫达非尼和苯丙胺-右旋苯丙胺分别改善了5.0[± 标准差（SD）2.7]分和4.4[± 标准差（SD）4.7]分；苯丙胺-右旋苯丙胺的非劣效性未得到证实（P = 0.11）。在严重程度、嗜睡、睡眠惰性、过度失眠严重程度指数和睡眠惰性问卷的评分变化方面，安非他明-右旋安非他明均无劣效。莫达非尼因不良反应导致的辍学率为31.8%（包括两次严重不良反应），苯丙胺-右旋苯丙胺为9.1%，P = 0.13。莫达非尼更常见的是焦虑，而苯丙胺-右旋苯丙胺更常见的是食欲抑制：结论：就主要结果而言，苯丙胺-右旋苯丙胺与莫达非尼的非劣效性未得到证实。不过，在疾病严重程度和症状的多个次要指标上，苯丙胺-右旋苯丙胺的疗效并不差。这些数据可为特发性嗜睡症和2型嗜睡症治疗的共同决策提供参考：注册：Clinicaltrials.gov 注册 (NCT03772314) 12/10/18。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.