• Stefano de Biase, Giovanni Merlino, Simone Lorenzut, Mariarosaria Valente, and Gian Luigi Gigli.
• University of Udine Medical School, Department of Experimental and Clinical Medical Sciences, Neurology Unit , Udine , Italy.
• Expert Opin Investig Drugs. 2014 Jun 1; 23 (6): 847-56.

IntroductionRestless Legs Syndrome (RLS) is a common neurological disorder that impairs nocturnal rest, causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by severe RLS, pharmacological treatment is mandatory.Areas CoveredThe present review is based on an extensive Internet and PubMed search from 1994 - 2014. It focuses on drugs currently in development for the treatment of RLS.Expert OpinionThe drugs currently available for treating RLS do not always allow the patient to obtain a dose capable of controlling the symptoms, particularly in the long term. There is still the need for effective and well-tolerated new drugs. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone has demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled with first-line drugs; it could be used as a long-term treatment option in severe cases of RLS for which alternative satisfactory drug regimens are unavailable. There is a paucity of data comparing medications in head-to-head trials to determine their relative effectiveness and adverse event profiles. Furthermore, there is also a need for further studies that evaluate nondopaminergic agonists and combination therapies for treating RLS.

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