Opioids to Treat Restless Legs Syndrome

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 RLS symptoms and can improve sleep when other drugs have stopped working.

Opioids are not prescribed for mild RLS, but may be given for intermittent, chronic persistent, or refractory RLS. These categories mean: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

Different opioids used to treat RLS

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

The opioids most often prescribed for intermittent RLS are low doses of codeine or tramadol. However, other drugs such as carbidopa/levodopa or sedatives such as Klonopin (clonazepam) or Restoril (temazepam) may be prescribed first.1

Opioids are not the first choice for chronic persistent RLS. But a low-dose of opioids may be added if the first-line choices do not control symptoms well or stop working after a time. First-line drugs for this type of RLS are  alpha-2-delta ligands.1

Opioids may be considered for refractory RLS once iron levels get a boost (if needed) and if dopamine agonists, alpha-2-delta ligands, and benzodiazepine do not work. Opioids that may be used include:1

  • Codeine, hydrocodone, or oxycodone
  • Morphine, oxymorphone, or hydromorphone
  • Methadone, buprenorphine, or fentanyl patch
  • Tramadol or pentazocine

What are the possible side effects of opioids?

Constipation, sleepiness, drowsiness, problems emptying the bladder, and changes to concentration are all possible with opioids. Dependency can develop when taking higher doses, but most people with RLS are only given low doses.1,4

These are not all the possible side effects of opioids. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment with opioids.

Things to know about opioids

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.

Opioids should not be prescribed to people with RLS who also have untreated or under-treated sleep apnea. Opioids can make obstructive sleep apnea worse or induce central sleep apnea.1

Opioids should not be prescribed for 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

Older adults may not be able to take opioids.1

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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Written by: Jessica Johns Pool | Last reviewed: January 2022