ArticleNature and science of sleep2025
Restless Legs Syndrome Patients with Early Onset Disease or a Relevant Family History Associated with Pramipexole Ineffectiveness but Not Pregabalin.
Article in Nature and science of sleep, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Objective: To identify factors associated with the ineffectiveness of pramipexole and pregabalin in patients with various subtypes of RLS. Methods: 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. Results: 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). Conclusion: 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.
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