Pharmacological and Nonpharmacological Treatments for Restless Legs Syndrome in End Stage Kidney Disease: A Systematic Review and Component Network Meta-Analysis.

BACKGROUND Restless legs syndrome (RLS) is common among patients with end stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and nonpharmacological treatments of RLS, but an updated meta-analysis has not been conducted. METHODS The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis and additive component network meta-analysis was performed. The evidence certainty was assessed using Confidence in NMA (CINeMA) framework. RESULTS A total of 24 RCTs with 1,252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction (MD: 16.82, 95% CI: 10.635-23.02) and high level of confidence. Other potential non-pharmacologic interventions including intradialytic stretching exercise (MD: 12.00, 95% CI: 7.04-16.97) and aromatherapy massage (MD: 10.91, 95% CI: 6.96-14.85) but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective (MD: 8.95, 95% CI: 1.95-15.85), which also improved sleep quality (SMD: 2.00, 95% CI: 0.47-3.53). No statically significant adverse events were detected. CONCLUSIONS The NMA supports that cool dialysate is appropriate to apply to treat patients with ESKD and RLS. Gabapentin is most effective pharmacologic intervention which also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.