Why are opioids used in the restless legs syndrome?

Low potency opioids can be effective for intermittent RLS.  For chronic persistent RLS the American Academy of Sleep Medicine give conditional support of low dose opioids.  The use of opioids is considered if there is:

• Refractory RLS:  Severe symptoms that fail to respond to standard first-line medications.

• Dopamine Agonist Augmentation:  When long-term use of dopamine drugs (like pramipexole or ropinirole) backfires, causing symptoms to become progressively worse, start earlier in the day, or spread to other body parts.  Opioids are frequently used to help bridge patients off dopamine agonists.

• Severe Painful Sensations:  When RLS manifests with severe pain or deep aching that doesn't yield to nerve-pain medications.

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Medical guidelines recommend:

• Methadone:  Commonly considered a gold standard for severe refractory RLS at very low doses (typically 5 mg to 20 mg daily).  It has a long half-life, providing consistent cover through the night with a low rate of dose escalation.

• Buprenorphine:  Used in low-dose formulations with a usual effective daily dose of 0.5 mg to 6 mg (sublingual or transdermal).  Its unique pharmacology provides strong efficacy with a lower risk of respiratory depression and less tolerance.

• Oxycodone IR: Short acting and may require multiple doses has a usual effective dose of 10 mg to 30mg.

• Extended-Release Oxycodone-Naloxone:  Low-dose, long-acting formulations have demonstrated strong clinical trial success in reducing RLS symptoms and improving sleep quality with a usual effective dose of 10 mg to 30 mg.

• Morphine: Intermediate acting may produce daytime sedation with a usual effective dose of 15 mg to 45 mg.

A large percentage of patients with severe refractory RLS experience profound or complete symptom relief with the use of opioids.  Opioids are generally well tolerated, with only 3% of patients needing a significant increase in dose during 5 years of use for RLS.  Opioids do not cause augmentation (where symptoms get progressively worse), which is why they are so valuable for severe RLS.  Long-term clinical studies on low-dose opioids for RLS show that addiction rates and the need to constantly increase the dose are extremely low compared to chronic pain treatment, provided there is proper medical oversight.  Opioids also have risks that require cautious use and clinical oversight. Opioids should be prescribed cautiously when used together with benzodiazepines, gabapentinoids, or other sedating agents.

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Side effects of opioids

The side effects of opioids in RLS are usually minimal due to the low doses.  However, potential side effects are nausea, vomiting, constipation, sedation, drowsiness, insomnia, sexual dysfunction, adrenal insufficiency, itch, gait unsteadiness (risk of falls), cognitive dysfunction, hallucination, mood disturbance, anxiety, myoclonus, cough reflex inhibition, dry mouth, bronchospasm, respiratory depression, worsening sleep apnoea, miosis, muscle rigidity and more.

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For other treatment options see the pages: