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Prescription Medications to Treat Restless Legs Syndrome

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By Editorial Team

3 min read

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

Restless legs syndrome (RLS) is one of the most common sleep disorders. It causes unpleasant sensations in the legs and an uncontrollable urge to move the legs. People often find these feelings hard to describe. They may mention aching, throbbing, itching, pulling, twitching, or tingling.1,2

There are several ways to treat restless legs syndrome (RLS), including lifestyle changes, devices, prescription drugs, and home remedies. It may take a combination of all of these to reduce the leg sensations and get a good night’s sleep. In general, medicine is most often prescribed only for moderate to severe RLS after non-drug options have not worked.

Prescription drugs for restless legs syndrome

If your RLS is moderate to severe, your doctor may suggest a prescription drug. Which drug you are prescribed depends on whether you have symptoms nearly every night or off and on. The drugs prescribed for RLS include:1,3

  • Alpha-2-delta calcium channel ligands such as gabapentin enacarbil, gabapentin, or pregabalin
  • Dopaminergic agents such as pramipexole, ropinirole, rotigotine
  • Carbidopa/Levodopa
  • Benzodiazepines
  • Opioids

Anti-seizure drugs for restless legs syndrome

Gabapentin enacarbil (Horizant®) is the only alpha-2-delta calcium channel ligand drug approved by the U.S. Food and Drug Administration (FDA) to treat moderate to severe RLS. It seems to work as well as the dopaminergic drugs without the danger of augmentation. Augmentation is a condition where RLS symptoms get worse even when taking higher and higher doses.1

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Other anti-seizure drugs such as gabapentin and pregabalin may also be prescribed for RLS. These drugs reduce creeping, twitching feelings and nerve pain.

Dopaminergic agents for restless legs syndrome

Dopaminergic agents are drugs that help regulate body movement. These drugs normally are used in people with Parkinson’s disease. People with RLS are given much smaller doses than people with Parkinson’s. The FDA has approved ropinirole, pramipexole, and rotigotine to treat RLS symptoms.1,3

Carbidopa/Levodopa for restless legs syndrome

Levodopa was the first drug formally tested to treat RLS. Now it is used in combination with carbidopa. While these drugs do work to treat the symptoms of RLS, they are not prescribed as often as other, newer drugs. However, levodopa is sometimes still prescribed for occasional use.

Augmentation and restless legs syndrome

Many of the drugs used for RLS come with side effects. Levodopa, anti-seizure drugs, and dopaminergic drugs tend to work less well over time even when taking higher doses. Sometimes, RLS symptoms get worse instead of better when a person takes higher doses of medicine. This is called augmentation.3

Benzodiazepines for restless legs syndrome

Benzodiazepines can help people with RLS sleep better. However, the side effects of benzodiazepines, such as sleepwalking and daytime sleepiness, mean it is not often prescribed for RLS. People with sleep apnea should not take benzodiazepines unless their sleep apnea is well-treated.1,3

Opioids for restless legs syndrome

Opioids may work in people who do not respond to other drug treatments for RLS. The potential for abuse means that doctors consider opioids only for people with severe RLS and monitor them closely.3

Iron supplements for restless legs syndrome

Many people with restless legs syndrome have low iron levels. Taking iron pills sometimes helps relieve the symptoms of RLS. While iron can be purchased over-the-counter (OTC) it should not be taken without a doctor’s supervision. That is because iron supplements can cause many side effects, including an upset stomach and constipation. If you do take iron pills, you should also take vitamin C. Vitamin C helps the body absorb the iron.4-9

Rarely, people with severe RLS and anemia may need intravenous (IV) iron. This is given over several weeks, and it often takes weeks to relieve RLS symptoms.3

Other treatments for restless legs syndrome

Home remedies are popular and often provide at least some relief from RLS sensations. Diet and lifestyle changes also help many people with RLS. This includes getting regular exercise or reducing caffeine and alcohol.1-3

Only 1 device, Restiffic foot wraps, is approved by the FDA to treat restless legs syndrome. It requires a prescription from your doctor.10,11

Treating secondary restless legs syndrome

Sometimes RLS is caused by another health condition. In these cases, treating the underlying cause of RLS relieves the leg discomfort. These conditions are known to cause RLS in some people:1-3

  • Anemia caused by low iron levels
  • Pregnancy
  • End-stage kidney disease
  • Diabetes
  • Multiple sclerosis
  • Rheumatoid arthritis
  • Parkinson’s disease
  • Peripheral neuropathy
  • Heart disease
  • COPD
  • Spinal cord injuries

Certain drugs can trigger RLS symptoms or make the leg sensations worse. This includes antihistamines, anti-nausea medicines, and certain antidepressants. You may need to avoid or change your prescription to find a drug that does not aggravate your RLS.1,2,12

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.