Improving sleep for patients with restless legs syndrome. Part II: meta-analysis of vibration therapy and drugs approved by the FDA for treatment of restless legs syndrome

Abstract

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.

Sleep improvement for restless legs syndrome patients. Part III: effect of treatment assignment belief on sleep improvement in restless legs syndrome patients. A mediation analysis

“…Vibration stimulation (VS) has been shown to improve sleep in patients suffering from restless legs syndrome (RLS) as measured by (1) the Medical Outcomes Study Sleep Problems Index II (MOS-II) scale and by (2) clinician evaluation (Part I). 1 Furthermore, it has been demonstrated that sleep improvement from vibration treatment was comparable to sleep improvement from US Food and Drug Administration (FDA)approved RLS drugs (Part II).…”

“…1 Furthermore, it has been demonstrated that sleep improvement from vibration treatment was comparable to sleep improvement from US Food and Drug Administration (FDA)approved RLS drugs (Part II). 2 The current study is a mediation analysis of the pooled clinical trial data described in Parts I and II of this series of articles. 1,2 At the end of each of the two vibration trials, patients were asked whether they believed they had been assigned a therapeutic pad or a sham pad.…”

“…2 The current study is a mediation analysis of the pooled clinical trial data described in Parts I and II of this series of articles. 1,2 At the end of each of the two vibration trials, patients were asked whether they believed they had been assigned a therapeutic pad or a sham pad. Belief about pad assignment was a putative mediator variable.…”

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

“…4,5 We found that the magnitude of sleep improvement with a vibrating pad (treatment) was greater than with a nonvibrating (sham) pad and was comparable to sleep improvement with US Food and Drug Administration-approved drugs in patients with moderately severe primary RLS. Pad assignment (treatment pad versus sham pad) and pad assignment belief (patient belief that a treatment or sham pad was assigned) both influenced improvement in Medical Outcomes Study Sleep Problems Index II (MOS-II) 6-8 sleep scores; however, pad assignment belief was more influential.…”

“…Indirect comparisons of RLS drug and VS trials are, therefore, justified, so long as the compared trials are of parallel design. For example, the indirect comparison of VS and drug studies made by Burbank et al 5 would be valid because the compared trials were both parallel designs.…”