Efficacy and safety of pharmacological treatments for restless legs syndrome in hemodialysis patients: a systematic review and meta-analysis

Background Restless Legs Syndrome (RLS) is highly prevalent among adults receiving maintenance hemodialysis and significantly impairs sleep, psychological well-being, and quality of life. While Western pharmacological treatments such as dopaminergic agents, gabapentinoids, and iron therapy are commonly studied, Traditional Chinese Medicine (TCM) is also widely used in clinical practice—particularly for syndromes corresponding to RLS such as blood deficiency (Xue Xu) , liver–kidney yin deficiency (Gan Shen Bu Zu) , and blood stasis (Xue Yu) . However, the evidence base for TCM pharmacologic interventions in hemodialysis-related RLS remains unclear. This systematic review and meta-analysis evaluated the efficacy and safety of pharmacological therapies, including any available TCM-related pharmacologic treatments, in adults undergoing hemodialysis. Methods A comprehensive search of PubMed, EMBASE, CENTRAL, Scopus, Web of Science, ClinicalTrials.gov , and Chinese-language databases was conducted from inception to January 2025. Eligible studies included randomized, quasi-experimental, and observational studies of pharmacologic therapies—Western medications or TCM-derived pharmaceutical preparations—administered for RLS in adults on hemodialysis. The primary outcome was change in International Restless Legs Scale (IRLS) scores; secondary outcomes included sleep quality, quality of life, dialysis adequacy, and adverse events. Random-effects meta-analyses, subgroup analyses, and GRADE assessments were performed. Results Sixteen studies ( n = 1,324) met inclusion criteria, with nine included in the quantitative analysis. Pharmacologic therapy significantly improved IRLS scores (MD –7.84), sleep quality (SMD –0.82), and quality of life (SMD 0.48). Gabapentinoids produced the largest symptom reductions, followed by dopaminergic agents and iron therapy. No treatment affected dialysis adequacy. Adverse events increased modestly (RR 1.28), highest with dopaminergic agents. Although the search identified several TCM-related clinical studies, none met criteria for inclusion in the meta-analysis due to lack of standardized RLS diagnosis, inconsistent outcome reporting, or mixed non-pharmacologic interventions. Thus, TCM pharmacologic treatments could not be quantitatively evaluated. Subgroup analyses by drug class demonstrated that gabapentinoids produced the largest reductions in RLS symptom severity, followed by dopaminergic agents and iron therapy. Bar plots illustrate these comparative effects on RLS severity, sleep quality, and quality of life. A heatmap further revealed that dopaminergic agents were associated with the highest frequency of adverse events, particularly nausea, hypotension, and augmentation. Conclusion Western pharmacologic agents—particularly gabapentinoids—are effective for managing RLS in hemodialysis patients. Dopaminergic agents are beneficial but limited by higher adverse event risks, while iron therapy offers moderate benefits with good tolerability. Although TCM is widely used for symptom patterns associated with RLS and shows theoretical promise, high-quality, hemodialysis-specific pharmacologic TCM trials are lacking. To support integrated Chinese–Western clinical practice, rigorous future RCTs of standardized TCM formulations are urgently needed. This study provides evidence to guide clinical decision-making and emphasizes the importance of individualizing treatment approaches to balance efficacy and safety for patients undergoing hemodialysis.