Madhaw Govind, Gupta Ravi, Dhamija Puneet, Kumar Niraj
Department of Neurology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
Sleep Sci. 2023 Jul 6;16(2):174-182. doi: 10.1055/s-0043-1770810. eCollection 2023 Jun.
Amantadine has both anti-glutamatergic and dopaminergic action and may improve restless legs syndrome (RLS). We compared the efficacy and adverse-effect profile of amantadine and ropinirole in RLS. In this randomized, open-label, 12-week flexible-dose exploratory study, RLS patients with international RLS study group severity scale score (IRLSS) > 10 were randomized to receive either amantadine(100-300mg/day) or ropinirole (0.5-2mg/day). Drug dose was increased until week-6 if IRLSS failed to improve by ≥10% of previous visit score. IRLSS change from baseline at week-12 was the primary outcome. Secondary outcomes included change in RLS-related quality of life (RLS-QOL) and insomnia severity index (ISI), along with clinical-global-impression of change/improvement (CGI-I), and proportion of patients with adverse-effects and resulting discontinuation. Twenty-four patients received amantadine and 22 received ropinirole. Both groups had a significant effect for visit*treatment arm (F (2.19,68.15) =4.35;P = 0.01). With a similar baseline IRLSS, both intention-to-treat (ITT) and per-protocol analyses revealed comparable IRLSS until week-8, with ropinirole appearing superior from week-10 to week-12 (week-12 IRLSS, amantadine vs ropinirole:17.0 5.7 vs 9.0 4.4;P < 0.001). ITT analysis at week-12 showed comparable proportion of responders (≥10% IRLSS reduction) in both groups (P = 0.10). Both drugs improved sleep and QOL, but week-12 scores favoured ropinirole [(ISI:14.4 5.7 vs 9.4 4.5; P = 0.001) ;(RLS-QOL:70.4 17.9 vs 86.5 9.8; P = 0.005)]. CGI-I at week-12 favoured ropinirole (Mann-Whitney U = 35.50, S. E = 23.05;P = 0.01). Four patients in amantadine and two in ropinirole group developed adverse effects, with resulting discontinuation in two patients on amantadine. The present study reports equivalent reduction in RLS symptoms with both amantadine and ropinirole until week-8, with the latter being superior from week-10 onwards. Ropinirole was better tolerated.
金刚烷胺具有抗谷氨酸能和多巴胺能作用，可能改善不安腿综合征（RLS）。我们比较了金刚烷胺和罗匹尼罗治疗RLS的疗效和不良反应。
在这项随机、开放标签、为期12周的灵活剂量探索性研究中，国际RLS研究组严重程度量表评分（IRLSS）>10的RLS患者被随机分为接受金刚烷胺（100 - 300mg/天）或罗匹尼罗（0.5 - 2mg/天）治疗。如果IRLSS未能比上一次就诊评分改善≥10%，则在第6周前增加药物剂量。第12周时IRLSS相对于基线的变化是主要结局。次要结局包括RLS相关生活质量（RLS - QOL）和失眠严重程度指数（ISI）的变化，以及临床总体印象变化/改善（CGI - I），还有出现不良反应及导致停药的患者比例。
24例患者接受金刚烷胺治疗，22例接受罗匹尼罗治疗。两组在就诊*治疗组方面有显著效果（F(2.19,68.15)=4.35；P = 0.01）。在相似的基线IRLSS水平下，意向性分析（ITT）和符合方案分析均显示，直到第8周两组的IRLSS相当，从第10周到第12周罗匹尼罗似乎更具优势（第12周IRLSS，金刚烷胺组与罗匹尼罗组：17.0 ± 5.7 vs 9.0 ± 4.4；P < 0.001）。第12周的ITT分析显示两组的有效应答者比例（IRLSS降低≥10%）相当（P = 0.10）。两种药物均改善了睡眠和生活质量，但第12周的评分显示罗匹尼罗更具优势[（ISI：14.4 ± 5.7 vs 9.4 ± 4.5；P = 0.001）；（RLS - QOL：70.4 ± 17.9 vs 86.5 ± 9.8；P = 0.005）]。第12周的CGI - I显示罗匹尼罗更具优势（曼 - 惠特尼U = 35.50，标准误 = 23.05；P = 0.01）。金刚烷胺组有4例患者出现不良反应，罗匹尼罗组有2例，金刚烷胺组有2例患者因不良反应停药。
本研究报告称，直到第8周，金刚烷胺和罗匹尼罗在减轻RLS症状方面效果相当，从第10周起罗匹尼罗更具优势。罗匹尼罗的耐受性更好。
