Opioids to Treat Restless Legs Syndrome

Reviewed by: HU Medical Review Board | Last reviewed: March 2023

Doctors may hesitate to prescribe opioids for restless legs syndrome (RLS) or any other condition these days. However, this group of drugs can be very effective in treating severe RLS symptoms or when other drugs have stopped working.1

Opioids are not prescribed for mild RLS but may be given for other categories of RLS. These categories are:1

  • Intermittent RLS symptoms disrupt quality of life enough to justify treatment and occur less than twice a week.
  • Chronic persistent RLS symptoms are frequent and severe enough to require daily treatment, usually twice a week or more.
  • Refractory RLS means symptoms are long-term and do not get better with one of the single drug treatments most often prescribed.

How do opioids work to treat RLS?

Opioids act on 3 types of receptors in the brain. A receptor is a port or dock where brain chemicals (neurotransmitters) can bind to brain cells. Opioids change how these receptors work, which reduces the symptoms a person with RLS feels.2,3


When opioids are prescribed for RLS, it is usually in doses much lower than what is prescribed for chronic pain.4

Opioids that may be used include:1

  • Oxycodone
  • Methadone
  • Tramadol

A low dose of tramadol is most often prescribed first, especially if the person also has chronic neuropathic pain. The next step up is oxycodone. Stronger opioids like methadone are prescribed as a last resort for severe, intense RLS. Severe symptoms most often occur in people experiencing augmentation.1

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Opioids come with many potential side effects, including:1

  • Nausea, constipation, and stomach upset
  • Sleepiness, drowsiness
  • Dizziness
  • Excessive sweating

Opioids have boxed warnings, the strictest warning from the US Food and Drug Administration (FDA). Opioids come with this warning because they have:1

  • A high risk of abuse, misuse, or overdose
  • Potential to slow or stop breathing

These are not all the possible side effects of opioids. Talk to your doctor about what to expect when taking opioids. You also should call your doctor if you have any changes that concern you when taking opioids.

Other things to know

Good sleep habits and lifestyle changes should always be a part of any overall treatment plan for restless legs syndrome. That is because good sleep habits and lifestyle changes can be used throughout life without dangerous side effects. Poor sleep habits can also make RLS symptoms worse.1,5

Opioids should not be taken with benzodiazepines.1

Opioids should not be prescribed to people with RLS who also have untreated or undertreated sleep apnea. Opioids can make obstructive sleep apnea worse or induce central sleep apnea. Your doctor may order a sleep test to check you for sleep apnea before prescribing an opioid.1

Opioids should not be prescribed to anyone with past substance abuse issues. Your doctor will likely require a drug screening test to make sure you are not already taking opioids before writing a prescription. Follow-ups may take place more often to monitor you for signs of abuse and other side effects.1,4

Research is underway to learn more about the use of low-dose opioids to treat RLS.2

Before beginning treatment for RLS, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

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