Restless Legs Syndrome Treatments and Medications

For most people, bedtime promises a welcome break from the day but not for people with restless legs syndrome. When they lie down, a crawling tingling or burning will begin in one or both legs along with an irresistible impulse to move. Pretty soon, they’re up on their feet walking, stretching—anything to get rid of the feeling. It’s a nighttime ritual millions of Americans suffer from every night, but for many, it can be resolved. A visit to a healthcare professional can start them on the road to resolution.

What is restless legs syndrome?

Restless legs syndrome (RLS), or Willis-Ekbom Disease, is a common and complex disorder characterized by an irresistible urge to move the legs, an urge often accompanied by unpleasant and abnormal sensations deep in the leg tissues such as itching, tingling, or crawling. The urge usually manifests at night or during long periods of sitting, such as driving or watching TV. Walking, stretching, moving around—all these help relieve both the urge and the sensations.

Because the symptoms worsen or only occur at night, RLS is often classified as a sleep disorder. In fact, RLS is a leading cause of insomnia. Because the urge to move the legs usually starts at night, people with RLS find it difficult to fall or stay asleep. Many also have Periodic Limb Movement Disorder (PLMD), a condition in which the legs periodically cramp and jerk around during sleep. Lack of sleep and daytime sleepiness are common experiences for people with RLS.

In the United States, three million people each year are diagnosed with restless legs syndrome (RLS), but healthcare professionals all agree that the condition is significantly underdiagnosed. The best guess is that anywhere from 5-10% of Americans have RLS. Many cases are mild and/or intermittent, but more severe and chronic cases can substantially reduce a person’s quality of life, leading to depression and even suicide.

RLS can be a temporary condition caused by some other problem. Secondary restless legs syndrome can often be resolved by correcting the underlying problem. Iron deficiency, folate deficiency, magnesium deficiency, pregnancy, nerve pain, diabetes, fibromyalgia, celiac disease, and end-stage kidney disease can all cause RLS. Some medications produce RLS as a side effect or worsen symptoms if already present. These include classes of antidepressants known as TCAs and SSRIs, medications that block dopamine—including many antipsychotics, and even some antihistamines. Alcohol, caffeine, and products containing nicotine have been known to worsen symptoms.

Some RLS cases have no identified cause. Called primary restless legs syndrome, or familial restless legs syndrome, the condition is chronic and probably inherited. It usually starts intermittently in childhood or early adulthood but the diagnosis isn’t made until much later as symptoms become more of a daily occurrence. Some may develop primary RLS later in life with more of a rapid onset and progression of symptoms.

RLS is universally considered a problem with the nervous system. Scientists have not quite pinned down the exact cause, but the most likely culprit in primary and some secondary RLS cases is dysfunction of the section of the brain that uses dopamine to conduct purposeful muscle movement. We know that other movement disorders like Parkinson’s disease, which result in involuntary movements, also occur because of a disorder in dopamine pathways.

The good news is that most cases of RLS are treatable. Many RLS symptoms caused by an underlying condition can be resolved. More severe cases of primary or familial RLS can be managed with neurological medication, but unfortunately, no cure exists.

How is restless legs syndrome diagnosed?

Restless legs syndrome is usually diagnosed from the symptoms. A physical exam and testing are only used to rule out other conditions.

Most patients will first bring the problem to a family practitioner, but RLS is definitively diagnosed and treated by specialists including neurologists, psychiatrists, and sleep specialists.

There are five symptoms required for a diagnosis of RLS:

• An intense urge to move the legs, often with abnormal feelings in the legs such as itching or creeping

• The urge begins or worsens with inactivity

• Symptoms are partly or completely relieved with walking or stretching; at least as long as the activity continues

• Symptoms worsen in the evening or at night or are only present in the evening or night

• Symptoms are not accounted for by any other condition

A medical history will help determine whether the condition is primary or secondary. The doctor will look for risk factors such as:

• Family history of RLS

• Pregnancy

• Nutritional deficiencies

• Kidney disease

• Medication use

• A history of other conditions

Family history strongly indicates the condition may be inherited. If other conditions are present, a healthcare provider may start by addressing those problems first.

The physical exam usually turns up normal results. The physician, however, will be looking for signs of other neurological conditions, such as Parkinson’s disease or a compressed spinal nerve (radiculopathy), that might be causing the symptoms.

There are no specific tests to diagnose RLS, but a physician will order tests to rule out other conditions or discover a possible cause for the RLS. The physician will order blood tests to measure serum ferritin (iron), magnesium, or folate levels, since deficiencies in any of these nutrients can cause RLS. Other substances in the blood might point to other causes such as diabetes or kidney problems. Nerve tests, such as a nerve conduction study or an electromyogram, may be performed to rule out other neurological disorders.

Finally, RLS patients with severe sleep disturbances or who have periodic leg movements during sleep may be referred to a sleep clinic. They will spend a night undergoing a polysomnogram—a sleep study. This test will quantify the person’s sleep patterns as well as how much the legs are moving during sleep, and can also be used to identify other underlying or contributing conditions.

Restless legs syndrome treatment options

There are several treatment options for restless legs syndrome, including lifestyle changes, dietary supplements, over-the-counter pain relievers, medical devices, and powerful neurological medications.

Treatment of the underlying cause

For secondary RLS, the treatment of choice is to manage the underlying condition causing the problem.

Many RLS patients may be given dietary supplements of iron, magnesium, or folate to reduce symptoms. Iron, in particular, is vital to the body’s production of dopamine, so iron supplementation is a common treatment for RLS.

If RLS is medication-related, the person will be taken off that medication. And finally, patients with kidney failure may be given short daily dialysis sessions to help reduce RLS symptoms.

RLS that occurs during pregnancy often resolves within four weeks after delivery.

Lifestyle changes

RLS symptoms can be minimized by lifestyle changes including avoiding caffeine, alcohol, and nicotine-containing products; exercising, stretching, self-massage, and good sleep hygiene. Mild RLS symptoms can be effectively controlled with over-the-counter pain relievers such as ibuprofen or acetaminophen.

Medications

RLS symptoms are believed to be generated by the brain because of a shortage of dopamine, a chemical that transmits signals between nerves to conduct purposeful movement. First-line treatment of chronic moderate-to-severe RLS consists of drugs that act like dopamine, called dopamine agonists, or by gabapentinoids, a type of anticonvulsant drug often used to relieve nerve pain. Patients who do not get results can be treated with low-dose opioids.

Physical therapy devices

Physical therapy devices can provide sufficient symptom relief to help people sleep at night, mostly through “counter-stimulation,” that is, creating sensations, such as vibrations, that “drown out” RLS sensations generated by the brain. These include vibrating pads (Relaxis), pneumatic compression sleeves, foot wraps (Restiffic), heating pads, and icing.

Restless legs syndrome medications

Medications are usually not required for mild or secondary restless legs syndrome other than supplements or OTC pain relievers. First-line treatments for chronic or severe RLS are dopamine agonists or gabapentinoids, anti-seizure drugs that can also relieve nerve pain. When all else fails, low doses of opioids can manage symptoms.

Dopamine agonists

RLS is believed to be primarily caused by a shortage of dopamine in the brain. Dopamine agonists (or dopaminergics) such as pramipexole, ropinirole, cabergoline, and rotigotine, are drugs that “mimic” dopamine in the brain. They are remarkably effective at reducing RLS symptoms and dramatically improve sleep. After a while, however, they will lose effectiveness and often worsen RLS symptoms, a phenomenon known as “augmentation.” Because of the risk of augmentation, dopamine agonists are prescribed for RLS at the lowest possible dose for the shortest period.

Gabapentinoids

Gabapentinoids were originally developed as anti-seizure (anticonvulsant) medications, but are now widely used to relieve pain. These drugs reduce the excitability of nerves in the spinal cord, effectively “quieting” RLS symptoms as well as other kinds of nerve pain. They do notrisk worsening RLS symptoms in the same way as dopamine agonists. For this reason, healthcare professionals are increasingly turning to gabapentinoids—Horizant (gabapentin enacarbil), Lyrica (pregabalin), and a generic formulation gabapentin, as first-line therapy to treat severe or chronic RLS.

Opioids

Low potency opioids like tramadol and hydrocodone, can be effective for treating intermittent cases of RLS symptoms on an as needed basis. For moderate to severe cases that cannot be successfully treated with dopamine agonists or gabapentinoids, the second line treatments are more potent opioids. These may be added on to other drug classes or used as monotherapy. Oxycodone and methadone are particularly effective at relieving RLS and improving sleep in situations of extreme symptoms, especially if a patient must be abruptly taken off a dopamine agonist. These medications also come with unique challenges for long-term use and generally the lowest doses possible should be used.

Other prescription medications

Medications which include levodopa (a molecule the body converts into dopamine) and benzodiazepines, such as clonazepam, were prescribed for RLS to treat symptoms or put patients to sleep. They are, however, rarely prescribed these days. Levodopa rapidly loses effectiveness and causes augmentation, and benzodiazepines have a high potential for abuse.

Symptom relief medications

People with mild RLS can manage nighttime symptoms with acetaminophen or with NSAIDs (nonsteroidal anti-inflammatory drugs) such as aspirin and ibuprofen.

Supplements

Most patients with RLS will be prescribed or advised to take an iron supplement. Iron is a critical component in the body’s production of dopamine. Magnesium or folate (vitamin B9) deficiency can also cause RLS, so supplements may be advised or prescribed.

What is the best medication for restless legs syndrome?

Restless legs syndrome is a complex neurological condition. Some of the most effective medications, dopamine agonists, lose effectiveness very quickly and could make the condition worse over time. Others have serious side effects. Many of the medications prescribed by doctors are not approved for RLS, so their effectiveness has not been proven. For all these reasons, the “best” medication for restless legs syndrome will depend on how well the patient responds to any therapy.

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Best medications for restless leg syndrome