Guideline sources The following summarized guidelines for the management of restless legs syndrome (RLS) are prepared by our editorial team based on guidelines from the American Academy of Neurology (AAN 2016). 1 2 3 3 3 3 4 Definition RLS is a neurologic disorder that is characterized by a strong urge to move one's legs, which is exacerbated during rest or inactivity. 2 Epidemiology RLS may be idiopathic, or may occur in the context of neurological disorders (such as spinal cord injury or stroke), obstructive sleep apnea, iron deficiency, pregnancy, chronic renal failure, and use of certain drugs (antidepressants, neuroleptics, cumulative dopaminergic agonists). 3 Pathophysiology The prevalence of RLS in the United States is estimated at 10%. 3 Disease course RLS results from alterations in the function of dopaminergic neurons within the CNS, which promote spinal hyperexcitability and result in spontaneous sensory and motor disturbances. 3 Prognosis and risk of recurrence https://web.pathway.md/diseases/rec6jL4TFXmuEO2E4 1/3 6/24/23, 2:57 PM Restless legs syndrome Pathway Loss of efficacy and augmentation are two main types of treatment failures occurring in patients receiving long-term treatment for RLS. Augmentation refers to a medication-induced worsening of the symptoms. The augmentation rate for pramipexole, ropinirole, and rotigotine is 65% at 10 years, 24% at 5 years, and 13% at 5 years, respectively. 3 4 Pathway Restless legs syndrome Management Guidelines 1. Medical management Indications for treatment: consider initiating a pharmacologic agent for symptomatic relief in patients with moderate-to-severe primary RLS. Ferrous sulfate and vitamin C: consider ferrous sulfate with vitamin C to alleviate symptoms in patients with RLS and serum ferritin 75 mg/L. C Dopaminergic agents: Consider pramipexole or rotigotine as first-line agents for the treatment of RLS, based on strong evidence. B Consider levodopa as a treatment option for patients with RLS, based on weak evidence. C Non-dopaminergic agents: Consider gapapentin as a first-line treatment agent for patients with RLS, based on strong evidence. B Consider pregabalin, ropirinole, or intravenous ferric carboxymaltose as treatment options for patients with RLS, based on moderate evidence. C Management of treatment failure: consider prolonged-release oxycodone/naloxone (where available) in patients with RLS who have not responded to other treatments, while weighing potential benefits against known opioid risks. C 2. Therapeutic procedures Device therapy: Consider pneumatic compression devices, initiated before symptom onset, in patients who desire nonpharmacological approaches to treatment of RLS. C Consider near infrared light therapy or repetitive transcranial magnetic stimulation. C https://web.pathway.md/diseases/rec6jL4TFXmuEO2E4 2/3 6/24/23, 2:57 PM Restless legs syndrome Pathway 3. Specific circumstances Patients with insomnia: consider using a pharmacologic agent that improves objective or subjective sleep parameters in patients with primary RLS and insomnia. Show 2 more Patients with periodic leg movements of sleep: Consider one of the following agents in patients with RLS and periodic leg movements of sleep: ropinirole B pramipexole, rotigotine, cabergoline, or pregabalin C levodopa C Patients with end-stage renal disease: Consider vitamin C and E supplementation (alone or in combination) as first-line treatment in patients with secondary RLS associated with end-stage renal disease on hemodialysis. C Consider ropinirole, levodopa, or exercise as treatment options in patients with secondary RLS associated with end-stage renal disease on hemodialysis. C Patients with psychiatric symptoms: consider ropinirole in patients with RLS and concomitant anxiety C or concomitant depression C Show 2 more Patients with augmentation symptoms: consider using pregabalin over pramipexole as a first- line treatment agent in patients in whom avoidance of augmentation is a deciding factor. C References 1. Winkelman JW, Armstrong MJ, Allen RP et al. Practice guideline summary: Treatment of restless legs syndrome in adults: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Dec 13;87 24 2585 2593. Open 2. Budhiraja P, Budhiraja R, Goodwin JL et al. Incidence of restless legs syndrome and its correlates. J Clin Sleep Med. 2012 Apr 15;8 2 119 24. Open 3. Guo S, Huang J, Jiang H et al. Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management. Front Aging Neurosci. 2017 Jun 2;9 171. Open 4. Bertisch S. In the Clinic. Restless Legs Syndrome. Ann Intern Med. 2015 Nov 3;163 9 ITC1 11. Open https://web.pathway.md/diseases/rec6jL4TFXmuEO2E4 3/3