Restless legs syndrome is a common sleep-related movement disorder that affects up to 15% of the population in North America, characterized by an uncomfortable urge to move the legs. This has been associated with poor quality of sleep and overall decreased quality of life. Chronic inflammation has been implicated as a key mediator of the low intracranial iron stores that characterize restless legs syndrome (RLS). Current medications for RLS target concomitant low serum iron levels or the dopaminergic pathway, but none target the inflammatory pathway. A novel therapy that focuses on inflammation would allow for additional research into the role of inflammation and cytokines in the development of RLS, and potentially unlock a new class of medications to treat patients with RLS. A small amount of prior evidence suggest that RLS symptoms improve with steroids, with associated improved quality of life, and with decreasing hepcidin levels as a biomarker of symptom severity. This pilot study, using an RCT design, serves to assess the efficacy of glucocorticoids in the alleviation of RLS symptoms, which would further anchor the association between RLS, inflammation, and one of its potential mediators - hepcidin. By giving a prednisone taper versus placebo, this study primarily aims to assess the effect of glucocorticoids on 1) decreasing RLS symptom severity. This study also aims to measure 2) objectively measured improvement in sleep, 3) changes in baseline and post-treatment hepcidin levels, and 4) prevalence of adverse events including psychosis and weight gain. RLS can be a debilitating disease and several non-traditional medications have been tested but with unequivocal results. Glucocorticoids may be an easily accessible and affordable key to better quality of life for RLS patients, especially those with refractory RLS.

Inclusion Criteria:

• Outpatient
• Refractory RLS defined as restless legs unresponsive to monotherapy with tolerable doses of first-line agents due to reduction in efficacy, augmentation, or adverse effects
• IRLS score greater than 15

Exclusion Criteria:

• Pregnancy
• Prescence of iron deficiency anemia
• History of Diabetes Mellitus Type 1 and Type 2
• History of uncontrolled hypertension
• Presence of immunosuppression (HIV or currently taking immunosuppressants)
• Any prior adverse reaction to glucocorticoids
• History of dementia or major psychiatric diseases with psychosis
• Lack of ability to understand the experimental protocol and to adequately communicate in English

IPD will not be shared to protect patient privacy and confidentiality.