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RLS can generally be well treated with medications such as the alpha 2 -delta calcium channel ligands (A2Ds) gabapentin, pregabalin, and gabapentin enacarbil or, if these are poorly tolerated or lack efficacy, the dopamine agonists (DAs) pramipexole, ropinirole, or rotigotine. Augmentation occurs when, after initiating treatment, the symptoms of restless legs syndrome happen earlier in the day, spread to other parts of the body (most commonly the arms), become more intense, and occur more quickly during periods of rest. Restless legs syndrome (RLS) is a common disorder. The population prevalence is 1.5% to 2.7% in a subgroup of patients having more severe RLS with symptoms occurring 2 or more times a week and causing at least moderate distress. It is important for primary care physicians to be familiar with the disorder and its management. Much has changed in the management of RLS since our previous revised Reprint courtesy of Restless Legs Syndrome Foundation. For more information about RLS visit our website at www.rls.org or call 512-366-9109. Recommendations for the Prevention and Restless legs syndrome (RLS) is a common condition characterized by an unpleasant urge to move the legs that usually occurs at night and may interfere with sleep. 1, 2 The American Academy of Sleep Medicine has published clinical features required for diagnosis (). 3 Restless legs syndrome is often familial and may be associated with lumbar spine disease, renal failure, and iron deficiency. 1 commonly produce augmentation, a progressive, long-term, iatrogenic worsening of RLS symptoms characterized by increasing severity as well as temporal and anatomic extension of symptoms. If dopaminergic augmentation of RLS is present, substitution of an A2D or opioid for the DA is the primary goal. Zusammenfassung: Die Therapieergebnisse beim Restless-legs-Syndrom sind nach wie vor unbefriedigend. Vor einer medikamentösen Behandlung sollten zugrunde liegende Erkrankungen oder Mangelzustände erkannt und behandelt werden. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19(3):205-13. Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med. 2004;5(1):9-14. Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. In this Review, we summarize state-of-the-art therapies for RLS in the context of the diagnostic criteria and available guidelines, based on knowledge ranging from Class I evidence for the e2 Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;165:1286–1292. e104 Tzonova D, Larrosa O, Calvo E, et al. Breakthrough symptoms during the daytime in patients with restless legs syndrome (Willis-Ekbom disease). Sleep Med 2012;13:151–155. The Restless Legs Syndrome Foundation released an updated algorithm for treating RLS patients in 2021 that sharply pivoted from dopamine agonist medications as first-line treatment. 2 The guidelines recommend alpha-2-delta ligands (gabapentin enacarbil, pregabalin, and gabapentin) as first-line agents for the treatment of chronic RLS, with Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial. Clinical Neuropharmacology. 2009;32:311–20. doi: 10.1097/WNF.0b013e3181b3ab16. In contrast, new evidence supporting three alpha-2-delta ligand calcium channel blockers — gabapentin enacarbil, gabapentin, and pregabalin — led the task force to support them as strong recommendations for RLS treatment. Figure 1 Body diagram showing sites of restless leg sensations.8 Box 1 International Restless Legs Syndrome Study Group consensus diagnostic criteria for restless legs syndrome 1. An urge to move the legs usually, but not always, accompanied by, or felt to be caused by, uncomfort-able and unpleasant sensations in the legs 2. Seven patients with RLS and dopaminergic drug-induced augmentation were treated with a gradual withdrawal of the offending drug and replacement with an alternative medication. Compared to sudden withdrawal, measured outcomes were similar but gradual tapering was better tolerated. Although the dopamine agonists, ropinirole and pramipexole have been the drugs of choice for patients with moderate to severe RLS, drug emergent problems like augmentation may limit their use for long term therapy. Restless legs syndrome (RLS) is a sensory-motor neurologic disorder present to a clinically significant degree in 2% to 3% of the adult population, more commonly with advancing age and in women, that dramatically affects sleep and quality of life. Addressing factors that worsen RLS (eg, iron deficiency, antidepressant or antihistamine administration, OSA) is an important first step in Experts gave strong recommendations for medications known as alpha-2-delta ligand calcium channel blockers: gabapentin enacarbil, gabapentin, and pregabalin. Unlike dopamine agonists, these drugs work by quieting the central nervous system and don’t cause RLS augmentation. Gabapentin enacarbil is a prodrug of gabapentin, converted to gabapentin after absorption, and thus avoids the nonlinear pharmacokinetics of gabapentin. It is administered as a single daily dose of 600 mg (300 mg in patients older than 65 years) at 5 pm to target adequate therapeutic levels at bedtime.
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