Prescription Medications to Treat Restless Legs Syndrome

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. It can even affect the arms. 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.

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
• Iron, including IV iron and oral iron preparations
• Opioids

Anti-seizure drugs for restless legs syndrome

Gabapentin enacarbil (Horizant^®) is approved by the U.S. Food and Drug Administration (FDA) to treat moderate to severe RLS. It seems to work well without the danger of augmentation. Augmentation is a condition where RLS symptoms get worse even when taking higher and higher doses.¹

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

Augmentation and restless legs syndrome

There was a change to the guidelines for RLS in 2024. Many of the drugs previously used for RLS came with side effects such as augmentation. This is when RLS symptoms worsen even on higher doses of the medications. This can be difficult to treat and is the reason why there was a change in the guidelines. Dopaminergic medications are no longer recommended as first-line treatment for RLS due to augmentation.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.^4-9

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.^4-9

There is also the concern about iron overload. If your doctor has recommended that you take iron pills, you should take them with vitamin C. Vitamin C helps the body absorb the iron.^4-9

Some people with severe RLS 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 and reducing both caffeine and alcohol.^1-3

There are 2 devices FDA-approved for RLS: Restiffic foot wraps and the Nidra peroneal stimulator. Both require 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

• 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.