Ying Miaofa, Wang Tiantian, Zhang Ting, Zhai Ziyang, Zhang Lisan
Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Department of Pharmacy, Qiantang Campus, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Nat Sci Sleep. 2025 Jul 25;17:1695-1708. doi: 10.2147/NSS.S532626. eCollection 2025.
Restless legs syndrome (RLS) is a complex condition characterized by significant heterogeneity. Factors that affect medication efficacy remain unclear; different RLS subtypes may respond differently to various drugs.
To identify factors associated with the ineffectiveness of pramipexole and pregabalin in patients with various subtypes of RLS.
This retrospective nested case-control study enrolled 257 RLS patients prescribed pramipexole or pregabalin between March 2019 and April 2024 at the sleep center of Sir Run Run Shaw Hospital. All patients completed a semi-structured questionnaire, underwent polysomnography and laboratory evaluations, and participated in a telephone survey. To represent iron-storage status, one principal component score that included five indicators of peripheral iron metabolism was extracted by principal component analysis. Treatment effectiveness was assessed using the Clinical Global Impression-Improvement (CGI-I) scale, with scores of 1-3 indicating effective treatment and higher scores reflecting ineffective treatment. Multivariate logistic regression was employed to assess the risk factors (or RLS subtypes) of medication ineffectiveness.
Of patients treated with pramipexole, 42.7% (70/164) reported poor outcomes. Early onset RLS (OR = 5.076; 95% CI, 1.836-14.033) and relevant family history (OR = 4.537; 95% CI, 1.556-13.437) increased pramipexole ineffectiveness risk. Among pregabalin users, 34.4% (32/93) reported ineffectiveness, which was associated with hemoglobin levels (OR = 1.039; 95% CI, 1.001-1.079).
These findings suggest that RLS patients with familial or early-onset characteristics may represent a distinct subtype that responds preferentially to α2δ ligands over dopamine agonists, supporting personalized treatment approaches based on clinical phenotyping.
不安腿综合征（RLS）是一种具有显著异质性的复杂病症。影响药物疗效的因素尚不清楚；不同的RLS亚型对各种药物的反应可能不同。
确定与普拉克索和加巴喷丁对不同亚型RLS患者治疗无效相关的因素。
这项回顾性巢式病例对照研究纳入了2019年3月至2024年4月期间在浙江大学医学院附属邵逸夫医院睡眠中心开具普拉克索或加巴喷丁处方的257例RLS患者。所有患者均完成了一份半结构化问卷，接受了多导睡眠图和实验室评估，并参与了电话调查。通过主成分分析提取了一个包含外周铁代谢五个指标的主成分得分，以代表铁储存状态。使用临床总体印象改善（CGI-I）量表评估治疗效果，得分1-3表示治疗有效，得分越高表明治疗无效。采用多变量逻辑回归评估药物治疗无效的危险因素（或RLS亚型）。
在接受普拉克索治疗的患者中，42.7%（70/164）报告疗效不佳。早发性RLS（OR = 5.076；95%CI，1.836-14.033）和相关家族史（OR = 4.537；95%CI，1.556-13.437）增加了普拉克索治疗无效的风险。在使用加巴喷丁的患者中，34.4%（32/93）报告治疗无效，这与血红蛋白水平有关（OR = 1.039；95%CI，1.001-1.079）。
这些发现表明，具有家族性或早发性特征的RLS患者可能代表一种独特的亚型，相对于多巴胺激动剂，其对α2δ配体的反应更优，支持基于临床表型的个性化治疗方法。
