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

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
• oxycodone-naloxone
• opioid
• tramadol

Article highlights

• Restless legs syndrome (RLS) is a common neurologic sensory-motor disorder, that can have a negative impact on sleep, quality of life and health.

• The drugs currently available for the treatment of RLS do not always allow to obtain an optimal control of symptoms, in particular in the 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.

• Pharmacological characteristics and patients’ comorbidities allow the physician to choose which opioid can be mostly effective and tolerated.

• 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.

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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.