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Intractable restless legs syndrome: role of prolonged-release oxycodone–naloxone

Authors de Biase S, Valente M, Gigli GL

Received 1 October 2015

Accepted for publication 25 January 2016

Published 23 February 2016 Volume 2016:12 Pages 417—425


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder

Stefano de Biase,1 Mariarosaria Valente,1,2 Gian Luigi Gigli1,2

1Neurology Unit, Department of Experimental and Clinical Medical Sciences, University of Udine Medical School, 2Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy

Abstract: Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs accompanied by uncomfortable sensations that occur at night or at time of rest. Pharmacological therapy should be limited to patients who suffer from clinically relevant symptoms. Chronic RLS is usually treated with either a dopamine agonist (pramipexole, ropinirole, rotigotine) or an α2δ calcium-channel ligand (gabapentin, gabapentin enacarbil, pregabalin). Augmentation is the main complication of long-term dopaminergic treatment, and frequently requires a reduction of current dopaminergic dose or a switch to nondopaminergic medications. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a recent Phase III trial, oxycodone–naloxone prolonged release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatments. The adverse-event profile was consistent with the safety profile of opioids. The most frequent adverse events were fatigue, constipation, nausea, headache, hyperhidrosis, somnolence, dry mouth, and pruritus. Adverse events were usually mild or moderate in intensity. No cases of augmentation were reported. Oxycodone–naloxone PR is approved for the second-line symptomatic treatment of adults with severe to very severe idiopathic RLS after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone–naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α2δ ligands are needed.

Keywords: augmentation, dopamine, oxycodone–naloxone, restless legs syndrome

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