Opioids in the treatment of restless legs syndrome: pharmacological and clinical aspects

Expert Opin Drug Metab Toxicol. 2016 Sep;12(9):1035-45. doi: 10.1080/17425255.2016.1198320. Epub 2016 Jun 17.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Absorption; augmentation; distribution; elimination; metabolism; methadone; morphine; opioid; oxycodone-naloxone; tramadol.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Delayed-Action Preparations
  • Dopamine Agents / therapeutic use
  • Drug Combinations
  • Humans
  • Naloxone / administration & dosage
  • Naloxone / therapeutic use
  • Oxycodone / administration & dosage
  • Oxycodone / therapeutic use
  • Quality of Life*
  • Restless Legs Syndrome / drug therapy*
  • Restless Legs Syndrome / physiopathology
  • Severity of Illness Index

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Dopamine Agents
  • Drug Combinations
  • oxycodone naloxone combination
  • Naloxone
  • Oxycodone