Opioids in the treatment of restless legs syndrome: pharmacological and clinical aspects.
BACKGROUND
Restless legs syndrome (RLS) is a common neurologic sensory-motor disorder that can have a negative impact on sleep, quality of life and health. In patients affected by severe RLS, pharmacological treatment is mandatory.


METHODS
The present review is based on a search using PubMed from 1993 to 2016. It is focused on pharmacological and clinical aspects of opioids used for the treatment of RLS.


CONCLUSIONS
The drugs currently available for the treatment of RLS do not always allow to obtain an optimal control of symptoms, in particular, when utilised for long-term treatment. 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 phase III trial oxycodone-naloxone prolonged-release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatment. It was recently approved for the second-line symptomatic treatment of 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 α-2-δ ligands are needed.
a Neurology Unit, Department of Experimental and Clinical Medical Sciences , University of Udine Medical School , Udine , Italy.
Stefano
S
de Biase
b Department of Neurosciences , 'S. Maria della Misericordia' University Hospital , Udine , Italy.
Giovanni
G
Merlino
a Neurology Unit, Department of Experimental and Clinical Medical Sciences , University of Udine Medical School , Udine , Italy.|b Department of Neurosciences , 'S. Maria della Misericordia' University Hospital , Udine , Italy.
Mariarosaria
M
Valente
a Neurology Unit, Department of Experimental and Clinical Medical Sciences , University of Udine Medical School , Udine , Italy.|b Department of Neurosciences , 'S. Maria della Misericordia' University Hospital , Udine , Italy.
Gian Luigi
GL
Gigli
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D015259:Dopamine Agents / Q000627:therapeutic use; D004338:Drug Combinations; D006801:Humans; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use; D010098:Oxycodone / Q000008:administration & dosage / Q000627:therapeutic use; D011788:Quality of Life; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D015259:Dopamine Agents; D004338:Drug Combinations; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
Absorption; augmentation; distribution; elimination; metabolism; methadone; morphine; opioid; oxycodone-naloxone; tramadol