Advancing synthetic therapies for the treatment of restless legs syndrome

ABSTRACT

Introduction: Restless Legs Syndrome/Willis-Ekbom disease (RLS/WED) is a common sensory-motor neurological disorder that impairs nocturnal rest causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by moderate to severe RLS/WED, a pharmacological treatment is mandatory.

Areas covered: The present review is based on an extensive Internet and PubMed search from 1996 to 2019. It is focused on drugs currently used and under development (phase III and beyond) for the treatment of RLS/WED.

Expert opinion: The drugs currently available for the treatment of the disease do not always allow for obtaining the optimal control of symptoms, in particular in the long-term treatment. Although initially effective, long-term dopaminergic treatment tends to wane over time and augmentation can occur. Updated international guidelines now recommend α2δ calcium channel ligand medications as the initial drug of choice. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS/WED insufficiently controlled with previous treatments. Head-to-head trials of different drugs, as well as more studies on nondopaminergic agents and combination therapy, are greatly needed. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS/WED, sparing stronger dopaminergic agents for later stages of the disease.

KEYWORDS:

• Augmentation
• α2δ calcium channel ligand
• dopamine
• investigational drugs
• iron
• MAO-B inhibitors
• oxycodone-naloxone
• restless legs syndrome

Article highlights

• Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a neurological sensory-motor disorder defined by an urgency to move the legs, usually combined with unpleasant sensations, which occurs or worsens during rest, and disappears with movement of the legs.

• Although initially effective, long-term dopaminergic treatment tends to wane over time and/or augmentation can occur.

• Updated international guidelines now recommend α2δ calcium channel ligand medications as the initial drug of choice.

• Monoamine oxidase B inhibitors could be good candidates for initial treatment of RLS/WED, sparing stronger dopaminergic agents for later stages of the disease.

• Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS/WED insufficiently controlled with previous treatments.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Referee disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.