What to do about restless legs syndrome


Bedtime is far from relaxing for women with this common condition.

Restless legs syndrome (RLS) is a sensory-motor disorder that causes an irresistible urge to move the legs, often accompanied by an uncomfortable “creepy-crawly” sensation. RLS affects 3% to 5% of adults and is twice as common in women as in men. Symptoms typically flare at night, just as you’re settling down in bed, but they may also arise when you’re resting in a chair. RLS not only causes discomfort and distress, but can also wreak havoc on sleep, causing daytime sleepiness and mood changes. Fortunately, certain lifestyle strategies can help you manage milder forms of RLS, and several medications can provide relief for more serious symptoms.

There’s a common mistaken belief that RLS refers to the jittery, leg-bouncing movements some people make when they’re anxious or overstimulated. Partly because of this, the RLS Foundation, a nonprofit organization that provides information about the disorder, is lobbying to change its name officially from RLS to Willis-Ekbom disease (see “What’s in a name?”). According to the foundation, the term “restless legs” trivializes a problem that can have a “severe and profound” impact on sleep and daily functioning.

What’s in a name?

English physician Sir Thomas Willis (1621–75) first described the condition now known as restless legs syndrome (RLS) in 1672. He wrote of “leapings and contractions” so intense that sufferers “are no more able to sleep than if they were in a place of the greatest Torture.” Other descriptions appeared in the medical literature in the 19th century, including one that attributed the problem to hysteria, a diagnosis that encompassed a range of psychological and physical problems. The Swedish neurologist Karl-Axel Ekbom (1907–77) introduced the term “restless legs” in 1944, in an article detailing the disorder’s features.

In January 2011, the RLS Foundation voted unanimously to change “restless legs syndrome” to “Willis-Ekbom disease” — to acknowledge these physicians’ contributions and to make it clear that the disorder is not simply a collection of symptoms (a syndrome), but a condition (disease) linked to genetic and neurochemical changes.


Symptoms of RLS

People with RLS describe the discomfort as feelings of creeping, prickling, pulling, itching, tugging, or stretching that typically occur below the knees and are felt deep within the legs. In severe cases, the arms are affected as well. Movement provides immediate relief, so people with the condition often fidget, kick, or massage their legs, or get up to pace the floor or perform deep knee bends.

Symptoms tend to worsen at the end of the day and peak at night, often within a half-hour after going to bed. In severe RLS, the symptoms strike earlier in the day — a challenge for people who must sit for a long time, as when attending meetings, performing desk work, or traveling long distances.


What causes RLS?

Primary RLS, the most common form of the disorder, is idiopathic, meaning that it has no known cause. But more than 40% of people with primary RLS have a family history of it, which suggests a strong underlying genetic component. Researchers have found five gene variants that predict a greater likelihood of RLS.

One theory is that primary RLS arises from an imbalance of dopamine, a neurotransmitter with many roles in the body, including the regulation of muscle movement. Some of the medications used to treat RLS work by mimicking the action of dopamine in the brain. RLS can also develop as a byproduct of other medical problems. One of the chief culprits in this secondary form of the disorder is iron deficiency, which may explain why the condition is more common in women.

“Women are more prone to low iron levels, mostly because of blood loss from menstruation,” says Dr. John Winkelman, medical director of the Sleep Health Center of Brigham and Women’s Hospital and associate professor of psychiatry at Harvard Medical School. Pregnancy, childbirth, and breastfeeding also deplete iron stores.

One small study found that older people with RLS had lower levels of ferritin (the main protein the body uses to store iron), and the lower the ferritin level, the worse the symptoms. Other research has shown lower ferritin levels in the spinal fluid of RLS sufferers and lower iron stores in their substantia nigra (one of the brain’s centers for movement control).

People with kidney disease who receive dialysis (a process that filters waste and removes excess water from the blood) have an increased risk of developing RLS. It’s also more common in people with diabetic neuropathy (nerve damage caused by diabetes). Multiple sclerosis, Parkinson’s disease, and certain rheumatic diseases (rheumatoid arthritis, lupus, and Sjögren’s syndrome) may also raise the risk, though the evidence isn’t conclusive. Some research has linked varicose veins to RLS, and preliminary studies suggest that treating them (with sclerotherapy injections or laser energy) may ease RLS symptoms, but the evidence so far is not definitive.

Finally, many common drugs can aggravate RLS symptoms, including caffeine, alcohol, and nicotine; the antihistamine drug diphenhydramine (Benadryl), which is found in many over-the-counter cold, allergy, and sleeping pills; prescription antidepressants such as amitriptyline (Elavil), fluoxetine (Prozac), and escitalopram (Lexapro); and antinausea medications, including metoclopramide (Reglan, others) and prochlorperazine (Compazine).

Calf stretch

Calf stretch

Stand two to three feet from a wall. Step forward with one foot and bend the knee, keeping the back knee straight. Place your hands on the wall for support and push your pelvis forward as far as you comfortably can, keeping your back heel on the floor. Hold for 10 to 20 seconds. Repeat five times on each side.


Diagnosing RLS

There are no specific tests for RLS — the diagnosis is based on symptoms — but your clinician will probably test your blood ferritin level and ask about your family and personal health history, including any drugs you take.

RLS can begin in childhood, but at that age, the problem is often misdiagnosed as attention deficit hyperactivity disorder or dismissed as “growing pains.” Even in adults, the diagnosis is often missed or delayed, especially if the symptoms are mild. Many people don’t seek treatment until their late 30s. There is no typical lifetime course for RLS. The symptoms often wax and wane, in both frequency and intensity.


Treating RLS

Treatments include iron supplements, lifestyle changes, and medications. If your blood ferritin is low (less than 50 ng/mL), you should be evaluated to find the cause, which could be a condition other than RLS or bleeding in the digestive or urinary tract. Because meat, eggs, and other animal proteins are major sources of iron in the diet, people who avoid these foods are also prone to low iron levels.

Dr. Winkelman recommends that RLS patients with low ferritin levels take 65 mg of elemental iron (about the amount in one 300-mg tablet of ferrous sulfate) once or twice a day on an empty stomach with a glass of orange juice. (The vitamin C in the juice boosts iron absorption.) Iron supplements can cause gastrointestinal distress, including cramps and constipation; if that’s a problem, start with a lower dose and gradually increase it to the recommended level. If you’re taking iron supplements, you should have your ferritin levels checked at least twice a year, as excess iron can cause other health problems.

Some people find that it helps to avoid caffeine, nicotine, and alcohol. Others get relief by distraction — reading or doing crossword puzzles, for example — but mentally stimulating activities won’t work so well when you’re trying to get to sleep. You may get some relief around bedtime by rubbing or squeezing the leg muscles, applying cold or warm compresses (or taking a warm bath), and stretching the calf muscles (see the illustration). It may also help to get moderate exercise during the day, such as walking or swimming.

Dr. Winkelman advises his patients with RLS to schedule activities that require prolonged sitting or reclining — airplane flights, beauty appointments, or massage or acupuncture treatments, for example — in the morning rather than the afternoon.

Medications prescribed for RLS, by medication class and side effects

Drug name Side effects Comment

diazepam (Valium)

clonazepam (Klonopin)

temazepam (Restoril)

Clumsiness or unsteadiness, dizziness, lightheadedness, daytime drowsiness, headache. Best for mild or intermittent symptoms. Do not take with alcohol or if you have sleep apnea. May be habit-forming; can trigger withdrawal symptoms if stopped abruptly.
Dopamine agents

cabergoline (Dostinex)

levodopa-carbidopa (Sinemet) pramipexole* (Mirapex)

ropinirole* (Requip)

Nausea, weakness, dizziness, abnormal body movements, cognitive and memory problems. Rare instances of impulse-control behaviors (e.g., obsessive gambling or shopping). Usually reserved for people with daily symptoms. Long-term use may lead to a worsening of symptoms.

zaleplon (Sonata) zolpidem (Ambien)

Headache, daytime drowsiness, dizziness, nausea, drugged feelings. Best for mild or intermittent symptoms. Do not take with alcohol, antihistamines, muscle relaxants, or sedatives.

oxycodone (OxyContin, Percocet) tramadol (Ultram, others)

Depressed breathing and circulation, dizziness or lightheadedness, next-day sedation, constipation, nausea, vomiting. Usually reserved for people with severe symptoms who don’t get relief from dopamine agents or benzodiazepines. Low risk of abuse in people with RLS. Do not take with alcohol or if you have sleep apnea.

gabapentin (Neurontin)

gabapentin enacarbil* (Horizant) pregabalin (Lyrica)

Dizziness, fatigue, sleepiness, trouble walking. Usually prescribed for people in whom dopamine agents no longer work. Can help ease “creepy-crawly” sensations and nerve pain.
*These drugs are FDA-approved to treat RLS. Other medications in this chart are approved for other conditions but have been found to be helpful in treating RLS.


Medications for RLS

Medications can help ease RLS symptoms, but finding the right one may require some trial and error. Also, some medications become less effective with time, so you may need to switch drugs periodically. The FDA has approved three drugs specifically for the treatment of RLS; your clinician may also prescribe medications that are approved for other conditions (see the table), either individually or in combination.

Two of the three drugs approved for treating RLS — pramipexole (Mirapex) and ropinirole (Requip) — are dopamine agonists, which means they help increase dopamine activity in the brain. But when taken for a long time, these drugs can make the condition worse — a phenomenon known as augmentation, in which symptoms start to appear earlier and earlier in the day, until, in severe cases, they’re present around the clock. Stopping all dopamine-related medications can solve the problem. A rare but potentially serious side effect of these drugs is the development of impulse-control behaviors, such as obsessive gambling or shopping. The behavior stops when the medication is discontinued.

The third medication approved for RLS — gabapentin enacarbil (Horizant), a long-acting version of the anti-seizure, anti-pain drug gabapentin — is often prescribed for people who no longer respond to dopamine agents.





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