Background: Vibratory stimulation pads have been shown to improve sleep in patients with restless legs syndrome (RLS) to a greater extent than sham therapy. The current gold standard of treatment is drugs approved by the US Food and Drug Administration (FDA) for use in RLS. The aim of this meta-analysis was to compare the efficacy and safety of vibratory stimulation pads, sham pads, and drugs approved by the FDA for use in RLS. Methods: We searched the PubMed, Embase, and clinical trial websites to identify the relevant randomized, double-blind, and placebo-controlled or sham-controlled studies. Fifteen studies including a combined total of 3455 patients with at least moderately severe primary RLS met our search criteria. Efficacy was defined as the standardized mean difference in sleep improvement between treatment and controls. Safety was assessed by comparing the odds ratios of any adverse events and adverse events leading to study withdrawal between treatment and control subjects. Results: Improvement in Medical Outcomes Study (MOS) sleep inventory scores from baseline was significantly greater in patients treated with vibratory stimulation pads than in those receiving sham pads (Hedges's g, standardized mean difference −0.39, P # 0.02). There was no difference in improvement in sleep scores between patients treated with vibratory stimulation pads (−0.39) and those receiving an approved RLS drug (−0.44, P . 0.70). The risk of any adverse event or withdrawal because of an adverse event was not significantly different between patients treated with vibratory stimulation pads and those assigned to sham pads (Mantel-Haenszel odds ratio 2.16 [P . 0.14] and 1.39 [P . 0.80], respectively). The odds ratios for patients reporting any adverse events and adverse events leading to withdrawal were not significantly different between patients treated with vibratory stimulation pads (2.16 and 1.39, respectively) and those who received approved RLS drugs (2.11 [P . 0.89] and 2.07 [P . 0.82], respectively, mixed-effects model). Conclusion: For patients with moderately severe RLS, vibratory stimulation pads were more effective than sham pads for improving sleep, as effective as FDA-approved RLS drugs, and as safe as both sham pads and FDA-approved RLS drugs.

Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Q between subgroups =0.25, P Q $0.62). Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Q between subgroups =4.59, P Q #0.03) and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Q between subgroups =5.50, P Q #0.02). Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover) had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials.