Restless Legs Syndrome and Other Sleep-Related Leg Disorders

WHAT ARE RESTLESS LEGS SYNDROME AND OTHER SLEEP-RELATED LEG DISORDERS?

Restless Legs Syndrome (RLS or Ekbom's syndrome)

Restless legs syndrome (also called RLS or Ekbom's syndrome) is an unsettling and poorly understood movement disorder affecting more than 5% of the general population. Although effective treatments are available, the condition frequently remains undiagnosed.

Symptoms of RLS. The core symptom of RLS is an irresistible urge to move the legs (medically known as akathisia). It is sometimes described as a sense of unease and weariness in the lower leg that is aggravated by restand relieved by movement. Specific characteristics of RLS include the following:

• Patients have described their RLS symptoms as "pulling, searing, drawing, tingling, bubbling, or crawling" beneath the skin, usually in the calf area, causing an irresistible urge to move the legs.These sensations can occur not only in the lower legs, but they can also affect the thighs, feet, and even the upper body. In fact, a small 2000 study suggested that nearly half of patients may experience RLS-type symptoms in the arms. Furthermore, restless arms may be the first symptom of RLS in some people.
• About 80% of patients with RLS also experience semi-rhythmic movements called periodic limb movement disorder, or PLMD. [For more details see discussion below.]
• Itching and pain, particularly aching pain, may be present.
• Patients experience symptoms when the legs are at rest and they feel most comfortable. (Conversely, movement brings relief.) Symptoms occur most often at night when lying down or sometimes during the day while sitting.
• Episodes of RLS most often occur between 10:00 PM and 4:00 AM at night, being at their worst right after midnight. They typically occur at 30 to 60 second intervals. They usually ebb by morning, although as the condition progresses, people may begin to experience symptoms during the day. They are always worse at night, however.
• At night the unpleasant sensations and the resulting uncontrollable urge to move the legs can often disturb sleep. Ignoring the need to move the legs usually only builds up tension until they jerk uncontrollably. If patients experience them during the day, they usually feel compelled to move his or her legs in order to relieve the symptoms, making it difficult to sit during air or car travel or through classes or meetings.

Late- and Early Onset Forms. Some experts now believe there are two forms of RLS, early- and late-onset, and that each has different characteristics:

• One study reported that people with the onset of RLS in adolescence or earlier tend to have a family history of the disorder and to have RLS without accompanying pain.
• Those with later onset tend not to have a family history of RLS. Their condition is more likely to have a neurologic basis and symptoms are more like to include pain in the lower extremities.

Periodic Limb Movement Disorder (PLMD)

About 6% of the population has periodic limb movement disorder, or PLMD (formerly known as nocturnal myoclonus). In PLMD, the symptoms are as follows:

• As with RLS, episodes usually occur during the night, peaking at around midnight.
• Leg muscles involuntarily and repetitively contract and jerk every 20 to 40 seconds during sleep. Such movements may last less than a second, or as long as 10 seconds.
• Unlike RLS, contractions in PLMD usually do not arouse patients.(PLMD is distinct from so-called hypnic jerks, which are brief and sudden movements that occur just as people are falling asleep and jolt them awake.)

Although 80% of RLS sufferers experience PLMD, only about 30% of people with PLMD also have RLS. Although the two conditions can be treated similarly there are some differences. PLMD, then, is considered to be a separate syndrome. PLMD is also very common in narcolepsy, a sleep disorder that causes people to suddenly fall asleep.

Nocturnal Leg Cramps

Cramps that awaken people during sleep are very common. They can be very painful and may cause a person jump out of bed in the middle of the night. They typically affect a specific area of the calf or the sole of the foot. [ See Box, What Are Nocturnal Legs Cramps? below.]

WHAT CAUSES RESTLESS LEGS SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER?

The primary cause of restless legs syndrome is not known. Researchers are investigating neurologic problems that may arise either in the spinal cord or the brain. One current theory on the cause of restless legs syndrome involves a deficiency in a brain chemical called dopamine. RLS probably has a genetic basis in many cases, particularly those that develop before age 40. When the onset of the condition occur in older adults, it most likely due to some neurologic problem.

Genetic Factors

People with restless legs syndrome often have a family history of the disorder. Researchers, however, have had little luck to date in detecting any specific genetic locations or factors that might be responsible for this condition. Of some promise are some studies of families with a strong history of RLS-related conditions. For example, research on Canadian and Italian families with RLS have led to identification of locations for genetically-based RLS on chromosomes 12 and 14.

Neurologic Abnormalities

Dopamine and Neurologic Abnormalities in the Brain. Other research suggests that neurologic abnormalities involved with RLS and PLMD originate in the brain. A variety of studies support the hypothesis that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS.Dopamine and serotonin unleash an array of nerve impulses that affect muscle movement. A similar effect is seen in Parkinson's disease, and indeed, drugs that increase dopamine are used for both disorders. (It should be noted that Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on. The two diseases then do not appear to share the same mechanisms.)

Neurologic Abnormalities in the Spine. Some research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. It had been thought that such abnormalities were likely to originate from nerve pathways in the lower spine. However, some patients with RLS commonly have symptoms in the arms suggesting that the upper spine may be involved as well. One 2001 study suggested that in patients with RLS and PLMD there is an abnormal over-excitable response along the entire spinal cord, which is triggered by sleep-related factors.

Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. Nevertheless, there is no evidence of a causal relationship.

Deficiencies in Iron Metabolism

Iron deficiency, even at a level too mild to cause anemia, has been linked to RLS in some people.Studies suggest, in fact, that RLS in some people may be due to impaired iron acquisition in cells that regulate dopamine in the brain. (Dopamine abnormalities are known to play a role in RLS--see above.) Some studies have reported RLS in between 25% and 30% of people with low iron levels. (In fact, the common connection between RLS and Parkinson's disease may derive from iron deficiencies in these patients.

Causes of Periodic Limb Movement Disorder (PLMD)

The cause or causes of PLMD are not clear. Some work suggests that it may be due to abnormalities in the autonomic nervous system (which regulates the involuntary actions of the smooth muscles, heart, and glands).

WHAT ARE THE RISK FACTORS FOR RESTLESS LEGS SYNDROME?

Gender and Age

Restless legs syndrome is estimated to affect between 2.5% and 15% of the general population. It is more common in women than in men, and its prevalence increases with age. An estimated 10% to 28% of those older than 65 are affected by the disorder.In about 40% of patients, RLS begins in adolescence, though it is uncommon in young children.

Family History

Up to two thirds of people with RLS have a family history of the disorder. In such cases, it is more likely to occur before age 40. (A family history of RLS is less likely in people who develop it as older adults.) It is also more common in populations from northern and western Europe, giving added support for a genetic basis for some cases of the disorder.

Attention Deficit Activity Disorder (ADHD)

RLS and periodic limb movement disorder in children are strongly associated with inattention and hyperactivity. One study suggested that a quarter of children diagnosed with attention-deficit hyperactivity disorder (ADHD) also has RLS or PLMD, and this may actually contribute to inattentiveness and hyperactivity. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. A 2001 study also reported an associated between adult attention deficit disorder and RLS. More research is needed to determine if RLS is a cause of some cases of ADHD or if it simply aggravates it. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine, which has been observed in both conditions. [For more information, see Well-Connected Report #30 Attention-Deficit Hyperactivity Disorder.]

Pregnancy

About 20% of pregnant women report RLS, which in most cases goes away after delivery. RLS in this population has been strongly associated with deficiencies in iron and with B vitamin folate (which in turn reduce iron levels). Symptoms typically disappear within a month after delivery.

Dialysis

Between 20% and 62% of people undergoing dialysis report restless legs syndrome. Symptoms often dissipate after a kidney transplant.

Anxiety Disorders

Anxiety can cause restlessness and agitation at night that can cause or strongly resemble restless legs syndrome.

Other Conditions Associated with RLS

The following medical conditions are also associated with RLS, although the relationships are not clear. In some cases, these conditions may contribute to RLS or they may have a common cause. In some cases, they may simply often coexist because of other risk factors:

• Osteoarthritis. About 72% of RLS patients have osteoarthritis.
• Varicose veins occur in 14% of RLS sufferers. Sclerotherapy treatments, in which medications are injected into affected veins, may relieve symptoms in such cases.
• Obesity.
• Diabetes.
• Hypertension.
• Hypothyroidism.
• Fibromyalgia.
• Rheumatoid arthritis.
• Emphysema.
• Chronic alcoholism.
• Sleep apnea and snoring.
• Chronic headaches.
• Brain or spinal injuries.
• Many muscle and nerve disorders. Hereditary ataxia, a group of genetic diseases that affect the central nervous system and cause loss of motor control, is of particular interest. Some experts believe that hereditary ataxia may supply clues for genetic causes of RLS.

Environmental and Dietary Factors

A number environmental and dietary factors can worsen or provoke RLS:

• Iron deficiencies. People who are deficient in iron are at risk for restless legs syndrome even if they don't have anemia.
• Folic acid or magnesium deficiencies.
• Smoking.
• Alcohol abuse.
• Caffeine. (Coffee drinking is specifically associated with PLMD.)
• Stress.
• Fatigue.
• Prolonged exposure to cold.

Medications

Drugs that worsen or provoke the condition include:

• Antidepressants.
• Antipsychotic drugs.
• Anti-nausea drugs
• Beta blockers.
• Antihistamines.
• Oral decongestants.
• Diuretics.
• Asthma drugs.
• Spinal anesthesia. Anesthesia-induced RLS typically resolves on its own within several months.

Risk Factors for Periodic Limb Movement Disorder (PLMD)

About 6% of the population has periodic limb movement disorder; they are usually elderly. As with RLS, a number of conditions may occur with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and degenerative neurologic diseases. Certain medications, including some antidepressants and anti-seizure medications, may also contribute to PLMD.

HOW SERIOUS IS RESTLESS LEGS SYNDROME?

Daytime Sleepiness and Its Consequences

Restless legs syndrome rarely results in any serious consequences. But in some cases, severe and persistent symptoms can cause considerable mental distress, chronic insomnia, and daytime sleepiness. [For more information, see Well-Connected Report #27, Insomnia.]

Sleep deprivation, and the daytime sleepiness that follows, is increasingly recognized as a cause of mood disruption and contributor to industrial errors and motor vehicle crashes. Insomnia costs the US approximately $13.9 billion each year in direct medical costs and unknown billions from decreased productivity and consequences of accidents.

Increased Risk for Accidents. As many as 200,000 automobile accidents in the US and 1,500 deaths from such accidents are caused by sleepiness. Studies continue to report that drowsy driving is as risky as drunk driving. In a major 2003 survey, 60% of young adults reported driving while drowsy and 20% dosed off while driving. In the study 1% of adults who dozed off reported having an accident because of it. (One study strongly suggested that it was habitual sleepiness, however, and not just being sleepy at the time of an accident that places people at higher risk.)

Effect on Daily Performance and Activities. Studies suggest that sleeplessness worsens many waking behaviors including the following:

• Avoidance of passive activities. Since RLS is worse when resting, people with severe RLS may avoid activities that involve long periods of sitting, such as going to movies or traveling long distances.
• Reduced concentration. Some experts report that deep sleep deprivation impairs the brain's ability to process information.
• Impaired task performance. One study reported that missing only two to three hours of sleep every night for a week significantly impaired performance and mood. An Australian study reported that 17 hours of sleep deprivation causes impaired performance levels comparable to those found in people who have blood alcohol levels of 0.10%, a level that defines intoxication in many US states.
• Effect on learning. Whether sleeplessness significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

Alcohol and Substance Abuse

Treatments for RLS. Medications used to treat RLS, such as the anti-anxiety agents (benzodiazepines) and opiates, can become habit forming and addictive.

Alcohol Abuse. A study found that people with insomnia were more likely to use alcohol for inducing sleep than people without insomnia. It should be noted, however, that a drink or two does no harm and may be helpful in people who are not at risk for alcoholism.

Psychiatric Effects

Some experts believe that many cases of RLS are due to underlying anxiety or depression. Studies in Swedish working-aged men and women reported that those with RLS were more apt to be socially isolated, to have frequent daytime headaches or depression, and to complain of reduced libido or problems related to sleepiness.

Furthermore, insomnia itself may increase the activity of the hormones and pathways in the brain that can produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of emotional disorders in some cases.

It is not clear if RLS is responsible for negative mood states or if anxiety or depression contributes to RLS. Certainly anxiety can cause agitation and leg restlessness that may even resemble RLS.

Emotional issues, however, are more likely to stem from RLS rather than the other way around.

HOW IS RESTLESS LEGS SYNDROME DIAGNOSED?

Taking a Sleep History

A diagnosis of restless legs syndrome or nocturnal leg cramps often relies solely on the patient's description of symptoms. In general, the recommended approach is first to take a sleep and personal history. The physician may begin an interview that may include the following questions:

• How would the sleep problem be described?
• How long has the sleep problem been experienced?
• How long does it take to fall asleep?
• How many times a week does it occur?
• How restful is sleep?
• What are the leg problems like (cramps, twitching, crawling feelings)?
• What is the sleep environment like? Noisy? Not dark enough?
• What medications are being taken (including the use of antidepressants and self-medications for insomnia, such as herbs, alcohol, and over-the-counter or prescription drugs)?
• Is the patient taking or withdrawing from stimulants, such as coffee or tobacco?
• How much alcohol is consumed per day?
• What stresses or emotional factors may be present?
• Has the patient experienced any significant life changes?
• Does the patient snore or gasp during sleep (an indication of sleep apnea, a condition in which breathing stops for short periods many times during the night and which may worsen symptoms of restless legs syndrome or insomnia)?
• If there is a bed partner, is his or her behavior distressing or disturbing?
• Is the patient a shift worker?

Keeping a Record of Sleep. To help answer these questions, the patient may need to keep a sleep diary. Every day for two weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. Recording sleep behavior using an extended-play audio or videotape can be very helpful in diagnosing sleep apnea.

A bed partner can help by adding his or her observations of the patient's sleep behavior.

Sleep Disorders Centers

In some cases of an uncertain diagnosis, high-risk patients may need to consult a sleep specialist or go to a sleep disorders center. At most centers, patients undergo an in-depth analysis, usually supervised by a multi-disciplinary team of consultants who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine. [ See Where Else Can Help for Restless Legs Syndrome Be Obtained? below.]

Among the signs that may indicate a need for a sleep disorders center are the following:

• Insomnia due to psychological disorders.
• Sleeping problems due to substance abuse.
• Snoring and sudden awakening with gasping for breath (possible sleep apnea).
• Severe restless legs syndrome.
• Persistent daytime sleepiness.
• Sudden episodes of falling asleep during the day (possible narcolepsy).
• At most sleep disorders centers, patients undergo an in-depth analysis, usually supervised by a multidisciplinary team of consultants who can provide both physical and psychiatric evaluations.

Polysomnography

Overnight polysomnography involves a number of tests to measure different functions during sleep. It is typically performed in a sleep center and may be performed to rule out sleep apnea or to confirm the effectiveness of RLS treatments.

The patient arrives about two hours before bedtime without having made any changes in daily habits. Polysomnography electronically monitors the patient as he or she passes, or fails to pass, through the various sleep stages. Polysomnography tracks the following:

• Brain waves.
• Body movements.
• Breathing.
• Heart rate. One study suggested that many patients with obstructive sleep apnea display distinctive heart rhythms as detected by electrocardiogram (ECG).
• Eye movements.

Changes in breathing and the levels of oxygen in the blood are also recorded. In patients with suspected sleep apnea, the sleep expert will track instances of apnea and hypopnea that last longer than 10 seconds. In general, if there are more than five episodes per hour, apnea is significant and if there are more than 15, the condition is serious.

Overnight polysomnography has been the gold standard for diagnosing obstructive sleep apnea in both adults and children. It is very labor intensive and expensive, however, and also misses snoring-induced arousals. A full set of tests including a night at a sleep clinic may cost $2,000 to $3,000 and is not always covered by insurance. In addition, some centers have waiting lists that can be months long.

Actigraphy

Actigraphy uses a small wristwatch-like device (e.g., Actiwatch) to monitor sleep quality in people with suspected RLS, periodic limb movement disorder (PLMD), insomnia, sleep apnea, and other sleep-related conditions. The device can be applied to the wrists or ankles. It measures muscle movements and records them during sleep. For example, with PLMD, it can provide information on total duration of movements, the number of occurrences, whether PLMD occurs simultaneously in both legs, and the effects on sleep.

It is not as accurate as polygraphy because it cannot measure all the biologic effects of sleep. It is more accurate than a sleep log, however, and very helpful for recording long periods of sleep.

Sleepiness Scale

The Epworth sleepiness scale uses a simple questionnaire to measure excessive sleepiness during eight situations.

Diagnosing Iron Deficiency Anemia and Its Causes

Because of the high association between restless legs syndrome and iron deficiency, a test for low iron stores should be part of the diagnostic work-up in RLS. There are two steps in making diagnosis in patients with symptoms of iron deficiency anemia:

• The first step is to determine if a person is actually deficient in iron.
• If iron stores are low, then the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low: The following findings are important in determining that a person is iron deficient:

• Blood cells viewed under the microscope are pale ( hypochromic) and abnormally small ( microcytic). They are also mostly uneven in shape. (These findings suggest iron deficiency, they but can also appear in anemia of chronic disease and thalassemia.)
• Hemoglobin and iron levels are low. (These findings further suggest iron deficiency, but they can also occur in cases due to anemia due to chronic disease.)
• Ferritin levels are low. Ferritin is a protein that binds to iron and low levels typically mean reduced iron stores. Note: High levels in the blood do not always mean sufficient iron stores. For example, pregnant women may have high ferritin levels into their third trimester but still be iron deficient. Ferritin levels may also be normal or even elevated in patients with inflammation from anemia of chronic disease, even if they also have low iron stores.
• A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in problematic patients, including the elderly with chronic diseases and possibly pregnant women.

Determining Causes of Iron Deficiency. When iron deficiency anemia is diagnosed, the next step is to determine what causes the iron deficiency itself.

• Dietary iron deficiency is most common in children and infants. It is rare in adults.
• Heavy menstrual or abnormal uterine bleeding is usually the cause of iron deficiencies in young women. Increased need for iron during pregnancy is also a common cause in this population.
• If internal bleeding is suspected as the cause, the gastrointestinal tract is usually the first suspect as the source. A diagnosis in such cases can be often be made if the patient has noticed blood in the stools, which can be black and tarry or red-streaked. Often, however, bleeding may be present but not visible. In such cases, stool tests for this hidden ( occult) blood are required. Additional tests may then be needed to diagnose the precipitating condition. Endoscopy, in which a fiber optic tube is used to view into the gastrointestinal tract, is helpful in many patients, particularly when the source of bleeding is unclear. Although endoscopy is not always performed in iron deficient patients if there are no signs of GI bleeding, one study suggested that this procedure could reveal other causes, including some cancers, in many patients.

If the patient's diet suggests low iron intake and other causes cannot be established using inexpensive or noninvasive techniques, then the patient may simply be given a monthly trial of iron supplements. If the patient fails to respond, further evaluation is needed.

Other Laboratory Tests

Certainly laboratory tests may be helpful in determining causes of RLS or conditions that rule it out. They include the following:

• Blood glucose tests for diabetes.
• Tests for kidney problems.
• Possibly tests for thyroid hormone and magnesium and folate levels.

Ruling Out Other Leg Disorders

In addition to other sleep-related leg disorders, a number of other medical conditions may have features that resemble restless leg syndrome.The physician will need to consider these disorders in making a diagnosis.

Peripheral Neuropathies. Peripheral neuropathies are nerve disorders in the legs or feet. They can be caused by a wide variety of conditions and can produce pain, burning, tingling, or shooting sensations in the extremities. Diabetes is a very common cause of painful peripheral neuropathies. Other causes include alcoholism, rheumatoid arthritis, systemic lupus erythematosus, amyloidosis, HIV infection, kidney failure, and certain vitamin deficiencies. Symptoms of peripheral neuropathies may mimic RLS. However, unlike RLS they are not usually associated with restlessness, nor are they relieved by movement, and they do not worsen at bedtime.

Deep Vein Thrombosis. Deep vein thrombosis is caused by a blood clot deep in the leg, usually in the thigh or calf. It may cause pain, swelling and aching in the leg where the clot has developed. It can occur in people with heart disease, with varicose veins, during pregnancy, in women from hormonal treatments, from injury to the leg, or from inactivity (such as after surgery or during long flights). Left untreated, this can be a very serious and even life-threatening condition.

Intermittent Claudication and Peripheral Artery Disease. Peripheral artery disease (PAD) occurs when atherosclerosis (commonly called hardening of the arteries) affects the feet and legs. In such cases, the arteries become blocked, obstructing oxygen-rich blood flow. Intermittent claudication is an important symptom of peripheral artery disease (PAD) and occurs in between a third and half of these patients. Claudication is taken from the Latin word "to limp". The name is used to describe the pain that occurs in PAD patients when they exercise, particularly during walking. In intermittent claudication, blood flow is sufficient to meet the needs of the person at rest. The result is leg pain during exercise, which is relieved by rest. [For more information see Well-Connected Report #102 Peripheral Artery Disease and Intermittent Claudication.]

Akathisia. Akathisia is a state of restlessness or agitation and feelings of muscle quivering. A condition called hypotensive akathisia is caused by failure in the autonomic nervous system. Unlike RLS, it occurs at any time of the day and usually only when the patient is sitting--not lying down. Akathisia itself can also be caused by drugs used to treat schizophrenia and other psychoses, with anti-nausea drugs, or when drugs to treat Parkinson's disease are withdrawn.

Painful Legs and Moving Toes Syndrome. A rare disorder affecting one or both legs, painful legs and moving toes syndrome is marked by a constant deep, throbbing ache in the limbs and involuntary toe movements. The discomfort may be mild or severe. It intensifies with activity and usually ceases during sleep. In most cases the cause is unknown, though it may arise from spinal injuries or herpes zoster infection. The condition is hard to treat, although the drug baclofen, combined with either clonazepam or carbamazepine, has shown some success. Other therapies that may help include orthotics for the shoes and transcutaneous electrical nerve stimulation (TENS).

Meralgia Paresthetica.An uncommon nerve condition, meralgia paresthetic is characterized by numbness, pain, tingling, or burning on the front and side of the thigh. It usually occurs on one side and is thought to be due to compression of the thigh nerve as it passes through the pelvis. It occurs most commonly between the ages 30 and 60, though all ages can be affected. It often goes away on its own with conservative treatment.

WHAT ARE THE NONMEDICAL TREATMENTS FOR RESTLESS LEGS SYNDROME?

The initial approach to a patient who complains of sleeplessness and restless legs syndrome is a nondrug one that aims at improving sleep and eliminating possible causes of RLS. A nondrug approach is a particularly important first step in elderly patients:

• The physician should first try to treat any underlying medical conditions that may be causing restless legs.
• If medications may be causing RLS, the physician should try to prescribe alternatives, if possible.
• If the cause cannot be determined, it is best to try sleep hygiene and relaxation methods, which are described below. Such approach provides added benefits, even if drug therapy is later required.

Possible Helpful Tips

Some people report help or relief from RLS with the following behaviors or devices:

• Hot baths or cold compresses.
• Ergonomic measures. For example, patients might find it useful to work at a high stool, where they can dangle their legs. In meetings or during air travel, it is helpful to obtain an aisle seat.
• A lumbar (lower back) corset. In one case, wearing a lumbar corset relieved symptoms in an older woman who elected not to take medications. Physicians suspect that the corset may have stimulated back muscles and mimicked the effects of walking and activity, which typically eases symptoms.
• Changing sleep patterns. Some patients report that symptoms don't occur if they sleep late in the morning, so, if feasible, changing sleep patterns may also be helpful.
• Avoiding caffeine, alcohol, and nicotine.

Alternative treatments that are sometimes advocated for RLS include acupuncture and massage. These treatments, however, have not been rigorously studied.

Dietary Approached for Iron Insufficiency

Because RLS is associated with iron insufficiency, people with the condition should be sure they have a diet that provides iron. Iron found in foods is either in the form of heme or non-heme iron:

• Heme Iron. Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
• Non-Heme Iron. Non-heme iron is less well absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables have only the non-heme form. Such vegetable products include dried beans and peas, iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The Effects of Food on Iron Absorption. The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron.

• Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
• Increasing intake of vitamin-C rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin-C rich foods are healthful and include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or six ounces of orange juice can double the amount of iron your body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on iron stores.)
• Foods containing riboflavin (vitamin B2) may help enhance the formation of hemoglobin from iron. Sources include liver, dried fortified cereals, and yogurt.

Certain nutrients impede the body's absorption of dietary iron. They include the following:

• Polyphenols (found in tea, coffee, red wine, berries, apples).
• Phytates (found in foods such as seeds, dried beans, soy, and bran). Such foods are typically high in fiber. (It is often believed that fiber itself impedes iron absorption, but researchers report that it has little or no effect.)
• Calcium. Calcium impairs the absorption of heme and non-heme iron. However, calcium intake must be quite high to cause any significant problems. For example, a 2002 study reported that cheese had no effect on iron absorption from meals rich in heme and non-heme iron.

The Effects of Cooking Methods on Iron. Cooking methods can enhance iron stores. Cooking in cast iron pans and skillets is well-known to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.

Exercise

Exercise earlier in the day may be one of the best ways to achieve healthy sleep. It should be noted that vigorous exercise and stimulation (including sexual activity) within one to two hours of bed time may worsen RLS. A study found that people who engaged in brisk walking for 30 minutes, four times a week, improved minor sleep disturbances after four months. Another study reported that sleep improved in a group of elderly people who exercised regularly. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

Behavioral Approaches for Preventing Insomnia

Prevention of sleeplessness is very much dependent upon the patient's ability to relax and learn the art of sleeping well. A number of behavioral methods are aimed at achieving these goals. Behavioral techniques can actually cure chronic insomnia and studies report their effectiveness in nearly all patients with primary chronic insomnia. Although medications are equally effective for helping people with insomnia to sleep, behavioral methods act faster. Behavioral methods are effective in all age groups, including elderly patients. In addition, medications cannot cure this condition and prolonged use frequently results in dependency.

Studies have reported that between 70% and 80% of those who are treated with non-drug methods experience improved sleep with an average treatment duration of only five hours over a four-week period. Furthermore, studies report that 75% of those who have been taking drugs are able to stop or reduce their use.

Specific Behavioral Methods. Proper sleep hygiene is the first step and should be accompany any behavioral method. [ See Box Sleep Hygiene Tips.] A number of approaches are available, but all have the same basic goals:

• To reduce the time it takes to go to sleep to below 30 minutes.
• Reduce wake-up periods during the night.

Some experts currently list the following behavioral methods in order of effectiveness:

• Stimulus control (standard treatment, which receives a high degree of physician support). It may also be helpful for some patients with secondary insomnia caused by a medical or psychiatric condition.
• Progressive muscle relaxation (studies and physician reports reflect a moderate degree of confidence in its effectiveness). It may be helpful for older individuals and some patients with secondary insomnia caused by a medical or psychiatric condition.
• Paradoxical intention (studies and physician reports reflect a moderate degree of certainty in its effectiveness).
• Biofeedback (studies and physician reports reflect a moderate degree of certainty in its effectiveness).
• Sleep restriction (evidence inconclusive on its value).
• Cognitive behavioral therapy (evidence inconclusive although studies are increasingly reporting benefits not only for improving sleep in the short term, but in help maintain healthy sleep).
• Sleep hygiene, imagery training, and cognitive training only (experts unable to recommend these approaches as sole therapy).

Stimulus Control. Stimulus control is now considered the standard treatment for primary chronic insomnia and may be helpful for some patients with secondary insomnia as well. The primary goal of stimulus control is to regain the idea that the bed is for sleeping. It involves the following:

• Go to bed only when ready to sleep or for sex.
• If unable to sleep within fifteen to twenty minutes, get up and go into another room. (People who find it physically difficult to get out of bed should sit up and do something relatively arousing, such as read.)
• Maintain a regular wake-up time no matter how few hours are spent sleeping.
• Avoid naps.

Progressive Muscle Relaxation. Progressive muscle relaxation is another technique for inducing sleep that is effective for many people. In one study, it was as effective as anxiety management training, a short-term behavioral technique. It takes about 10 minutes and involves the following:

• Focus first on a specific muscle group, typically with the muscles in one foot. Inhale and tense the muscle group for about eight second until the muscles start to shake and be mildly painful. (Do this gently. It is not intended to cause severe muscles contractions.)
• Release the muscles quickly and let them become loose and limp. Stay relaxed for 15 seconds and then repeat the same muscle group.
• Focus on the next muscle group and repeat the sequence. Move progressively from each foot and leg up through the abdomen, chest, then to each hand and arm and then to the neck and shoulders and face.

Paradoxical Intention. Paradoxical intention is a psychological approach that is based on doing the opposite of what one wants or fears and take it to extreme. The first step is to make a plan to take such a paradoxical approach to insomnia.

• Instead of going through activities leading to sleep, the patient prepares for staying awake and doing something energetic.
• In some cases, people may take specific psychological barriers to sleep to an extreme limit. For example, if worry is a factor in insomnia, the patient intensifies the worries.

Biofeedback. Biofeedback is also effective but requires being monitored with an electroencephalogram (EEG), a device that measures brain waves. Patients are given feedback to recognize certain states of tension or sleep stages so that they can either avoid or repeat them voluntarily.

Sleep Restriction Therapy. Sleep restriction therapy may be effective, although evidence is inconclusive. In one 2001 study, patients practiced sleep hygiene and sleep restriction. Sleep hygiene was very helpful during the first two months while sleep restriction led to sustained benefits and deeper sleep. The approach is a systematic method for achieving sleep and restricting the time spent in bed.

The first step is to calculate a person's sleep efficiency number:

• Keep a sleep diary for 14 days. Then calculate the average hours of actual sleep and hours in bed. Then divide the average hours slept by the hours in bed. The result, given as a percentage, is the sleep efficiency number. (For example, if a patient sleeps an average of five hours out of seven hours in bed then the result is .714 and the sleep efficiency percentage is 71%.)
• The patient's goal is to achieve sleep efficiencies of between 85% and 90%, which means only 10% to 15% of the time is spent staying awake in bed. (Sleep efficiency in older people may fall normally somewhere between 75% to 85%.)

To achieve this goal, the patient takes the following actions:

• Begin by going to bed 15 minutes later than usual the first week.
• If 85% sleep efficiency isn't reached by the end of the week, add another 15 minutes before going to bed. Refrain from going to bed even if tired, although bedtime should not be reduced below five hours.
• Once efficiency reaches 90% or more, then begin to go to bed 15 minutes earlier each week.

Other parts of the program include stopping any sleep medications and following good sleep hygiene. [ See Box Sleep Hygiene Tips.] People using this treatment have reported lasting improvements after just eight weeks and studies report that it is significantly more successful than relaxation techniques.

Cognitive-Behavioral Therapy. Cognitive behavioral therapy (CBT) is a form of therapy that emphasizes observing and changing negative thoughts about sleep (such as, "I'll never fall asleep"). It also employs actions intended to change behavior. Studies have been mixed on its effectiveness, although a major 2003 analysis of six trials suggested that it might be helpful for older adults. As another example, a 2002 study reported that CBT used alone or in combination with medications resulted in improved sleep efficiency and better on-going maintenance of healthy sleep compared to medication alone or sham treatment. In other studies, CBT has even helped post-traumatic stress victims and people with insomnia caused by chronic pain, who are all commonly resistant to most therapeutic maneuvers. The success of this approach rests strongly on the skill of the therapist. The long-term benefits of CBT are not known, and refresher sessions may be needed.

Using Imagery. A 2002 study enrolled people whose chronic insomnia was associated with unwanted thoughts and worries. They were given specific positive mental tasks that gave them a sense of positive control (as opposed to their real life concerns, which felt out of their control.) Those images distracted them and allowed them to fall asleep faster. In support of this approach, a 2002 study evaluated patients with insomnia who were given a problem before sleep. One group was asked to think of the problem in images and the other in words. The group who used imagery fell asleep more quickly and woke up with less anxiety.

Sleep Hygiene. The term sleep hygiene is used to describe simple behaviors that may help everyone improve their sleep.

WHAT ARE THE MEDICATIONS FOR RESTLESS LEGS SYNDROME?

The American Academy of Sleep Medicine recommends medications for RLS or periodic limb movement disorder (PLMD) only for persons who fulfill strict diagnostic criteria, and who experience excessive sleepiness that occurs as a result of these conditions. Little is known about the best way to treat RLS but some experts suggest the following:

• Over-the-counter pain relievers and possibly mineral and vitamin supplements (particularly folic acid in people who might be deficient) should be tried first.
• People with RLS should be tested for iron deficiency and, if they are, treated with oral iron supplements.
• Dopaminergic agents (drugs that increase levels of dopamine) are the standard agents to date for treating severe RLS, PMLD, or both. In either case they provide up to 100% relief. They include levodopa (L-dopa) and agents known as dopamine receptor agonists. Some experts then recommend regular use of dopamine receptor agonists for RLS patients who experience nightly symptoms and fast-acting L-dopa for those whose symptoms occur only occasionally.
• If dopaminergic agents fail or for patients who have frequent--but not nightly--symptoms, other agents may be helpful. These include opiates (pain relievers), benzodiazepines (anti-anxiety drugs), or anticonvulsants.

Over-the Counter Drugs and Supplements

NSAIDs. Before taking stronger medications, people should try over-the-counter pain relievers, such as acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen (Advil, Motrin, Rufen), naproxen (Anaprox, Naprosyn, Aleve), and ketoprofen (Orudis KT, Aktron).

Over-the Counter Supplements. The following supplements may have some benefit:

• Some people report that vitamin E (800 to 1200 IU per day) may help.
• Calcium, magnesium, or potassium supplements have helped some people.
• People who have folate deficiencies should take supplements of folic acid. This is particularly important during pregnancy, when folate deficiencies have been associated with RLS. (And, more importantly, deficiencies also increase the risk for birth defects in the infant.)

Iron Supplements

In people with RLS who are also iron deficient, iron supplements can produce a significant reduction in symptoms. They should be used in these patients, however, only when dietary measures have failed. They do not appear to be useful for RLS patients with normal or above normal iron levels. One interesting study, however, reported that high-dose intravenous iron therapy improved symptoms in nearly all patients with normal iron levels, suggesting that iron therapy may be useful in general for RLS. It should be noted, however, that iron replacement therapy can cause gastrointestinal problems, sometimes severe ones. Excess iron may also contribute to heart disease, diabetes, and certain cancers.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

• Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
• FerroSequels contains a stool softener, which helps prevent constipation.
• Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
• Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
• Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. A reasonable approach for patients with RLS is to take 65 mg of iron (or 325 mg of ferrous sulfate) along with 100 mg of vitamin C on an empty stomach three times a day.

IMPORTANT: As few as three adult iron tablets can poison children, even fatally. This includes any form of iron pill. No one, even adults, should take a double dose of iron if one is missed.

Tips for taking iron are as follows:

• For best absorption, iron should be taken between meals. (Iron may cause stomach and intestinal disturbances, however, and some experts believe that low doses of ferrous sulfate can be taken with food and absorbed without side effects.)
• One should always drink a full eight ounces of fluid with an iron pill.
• Tablets should be kept in a cool place. (Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.)
• One study suggested that iron supplements impeded the absorption of non-heme iron (found in legumes and other vegetables) but not heme iron (contained in meat).

Side Effects. Common side effects of iron supplements include the following:

• Constipation and diarrhea are very common. They are rarely severe, although iron tablets can aggravate existing gastrointestinal problems such as ulcers and ulcerative colitis.
• Nausea and vomiting may occur with high doses, but can be controlled by taking smaller amounts. Switching to ferrous gluconate may help some people with severe gastrointestinal problems.
• Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
• If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occur, gastrointestinal bleeding may be causing the iron deficiency and the patient should call the physician promptly.
• Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength tablets.

Interactions With Other Drugs. Certain medications, including antacids, can reduce iron absorption. Iron tablets may also reduce the effectiveness of other drugs, including the antibiotics tetracycline, penicillamine, and ciprofloxacin and the anti-Parkinson's Disease drugs methyldopa, levodopa, and carbidopa. At least two hours should elapse between doses of these drugs and iron supplements.

Supplementary Agents. The following agents may improve iron absorption:

• Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate therapy will improve absorption of iron stores. Ascorbic acid added to iron therapy, however, may exacerbate some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects.
• Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. (Some evidence for this suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.)

Levodopa and Other Dopaminergic Agents

Dopaminergic agents increase the availability of the brain chemical dopamine and are the standard agents used for severe RLS and PLMD. These drugs significantly reduce the number of limb movements per hour and improve the subjective quality of sleep. Patients with either condition have experienced up to 100% reduction in symptoms.However, these drugs, which are ordinarily used for Parkinson's disease, can have severe side effects. They do not appear to be as helpful for RLS related to hemodialysis as RLS from other causes.

Levodopa (L-Dopa). The drug levodopa (L-dopa) is often used for severe RLS. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are shown to be well tolerated and safe.)

Patients typically start with a very low dose taken one hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended form or to take it again during the night.

Levodopa has a rapid onset of action, and effectiveness is usually achieved within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep.

Dopaminergic Receptor Agonists. Agents known as dopamine receptor agonists are increasingly being used as alternatives to L-dopa. They have fewer side effects, including rebound effect, and augmentation.

They have been shown to relieve symptoms in more than 70% of patients. However, they are usually more expensive than L-dopa.These drugs include Pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), cabergoline (Dostinex),and tolpicone (Tasmar).Studies on some of these agents report the following:

• Pergolide is as effective Sinemet and has fewer side effects, though nausea, dizziness, and nasal stuffiness are common. It also seems to produce fewer of the rebound and augmentation effects of levodopa, particularly at higher doses.Benefits persist for at least a year.
• Pramipexole is the most potent drug yet used for RLS and has resulted in dramatic improvement in symptoms. It seems to be very effective in improving sleep and may also reduce periodic limb movement. A long-term, follow up study showed the drug continued to be effective for RLS, even after seven months of use. Pramipexole also appears to have antidepressant properties. The drug is used at much lower doses than when used for Parkinson's disease, so severe long-term side effects are rare.
• Cabergoline is also showing promise. In one study, cabergoline was used for RLS after levodopa had either failed or resulted in increased symptoms. Patients in the study reported relief or freedom from symptoms after four weeks of use.

Other Dopamine Agonists. Rotigotine is a unique dopamine agonist that is being developed in patch form for RLS and Parkinson's disease. Other dopamine agonists that have shown some promise in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal), although these are not currently available in the U.S.

Regimens. L-dopa is fast acting and takes only 15 to 30 minutes before it is effective. The dopamine receptor agonists take at least two hours to become effective. Some experts then recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms and L-dopa for those whose symptoms occur only occasionally.

Side Effects. Common side effects of all these drugs vary but may include feeling faint or dizzy (especially when standing up), headaches, abnormal muscle movements, rapid heartbeat, insomnia, bloating, chest pain, and dry mouth. Nausea may be especially common; adding the drug domperidone may help to relieve this side effect. Because these drugs may also cause daytime drowsiness, special care should be taken when driving.In rare cases, they can cause hallucinations or lung disease.

Dopaminergic agents may also have the following side effects, which can be limiting factors in the value of these medications for RLS. (They tend to be more severe with L-dopa than the newer dopamine receptor agonists.):

• Rebound Effect. The rebound effect causes increased leg movements at night or in the morning as the dose wears off.
• Augmentation. Long-term use of these agents may eventually intensify (augments) symptoms of restless legs syndrome in the late afternoon or evening. Symptoms of restlessness, in severe cases, extend to the upper part or the whole body and may occur when walking. About 20% of patients who take the dopamine receptor agonists have reported augmentations symptoms compared to 80% who take L-dopa. As the newer agents are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa. In general, however, occasional use of any agent poses a very a low risk for augmentation.
• Tolerance (Loss of effectiveness). Long-term use can lead to loss of effectiveness. Adding a drug called entacapone (Comtan) may prolong the duration of action of carbidopa-levodopa therapy (Sinemet), but it can cause nausea.

Using the lowest dose possible can minimize these effects.

Withdrawal Symptoms. Patients who withdraw from these agents typically experience very severe RLS symptoms for the first two days after stopping. RLS eventually returns to pre-treatment levels after about a week. The longer the drugs have been taken, the worse the withdrawal symptoms.

Benzodiazepines

Benzodiazepines, such as clonazepam (Klonopin), are commonly called hypnotics and are used for insomnia and anxiety. They may be helpful for some patients with RLS that disrupts sleep.Clonazepam may be particularly helpful for children with both periodic limb movement disorder and symptoms of attention-deficit hyperactivity disorder. It also appears to be helpful for RLS patients who are undergoing hemodialysis.

Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long- or short-acting. They include the following:

• The drugs may increase depression, a common co-condition in any case in many people with insomnia.
• Breathing problems may occur with overuse or with people with pre-existing respiratory illness.
• Long-acting agents have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
• Memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states have been reported after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
• Because these drugs cross the placenta and enter breast milk, pregnant nursing women should not use them. An association was reported between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns.
• In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol, and some medications, like the ulcer medication cimetidine, can slow the breakdown of the benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last one to three weeks after stopping the drug and may include the following:

• Gastrointestinal distress.
• Sweating.
• Disturbed heart rhythm.
• In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes one to two nights of sleep disturbance, daytime sleepiness, and anxiety. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Potent Pain Relievers

Narcotics. Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are sometimes prescribed for severe cases of RLS. They may also be a good choice if pain is a prominent feature.Some evidence also suggests they reduce the frequency of periodic leg movements.

There are two types of narcotics, both of which have been used in RLS:

• Opiates, which are derived from natural opium (e.g., morphine and codeine). Some patients report relief with the use of the opiate fentanyl (Duragesic), used in skin patch form. An implanted abdominal pump (Isomed) uses morphine and an anesthetic called bupivacaine. Investigate work is showing promise for patients with severe RLS.
• Opioids, which are synthetic drugs. The most common example is oxycodone (Percodan, Percocet, Roxicodone, Oxycontin). Apomorphine is a morphine derivative. In one study, it was administered subcutaneously (under the skin) at night and reduced nocturnal discomfort and leg movements in some patients.

Although the use of narcotics for severe RLS is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse, even when they are prescribed long-term. The use of such agents may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Patients on long-term opiate therapy should also be monitored periodically for sleep apnea, a condition that causes breathing to stop for short periods many times during the night and which may exacerbate symptoms of RLS, insomnia, and other complaints.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. In one study, tramadol was very effective for RLS and produced few or no side effects. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) Nevertheless, withdrawal after long-term use (e.g., over a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome itself.

Antiseizure Agents

Antiseizure drugs, such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol), relax blood vessels and are being tested for RLS. Gabapentin, a newer antiseizure drug, is showing particular promise for mild to moderate RLS.A well conducted 2002 study reported that it improved RLS symptoms and sleep, particularly in patients who also experienced pain. It was also effective for periodic leg movement disorder.

Side Effects. All antiseizure agents have potentially severe side effects and should be tried only after non-drug methods have failed. Side effects of many anti-seizure agents include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). Some can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazepine.

Other Agents

Selective Serotonin Reuptake Inhibitors (SSRIs) and Similar Antidepressants. Imbalances in the neurotransmitter serotonin have been associated with RLS, and the common antidepressants known as SSRIs, which increase serotonin levels in the brain, may be tried. One study found that SSRIs reduced RLS in 58% of patients and eliminated symptoms in 12%. Oddly, however, RLS became worse in another 12%. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa, Cipramil).

Bupropion (Wellbutrin), a newer so-called designer antidepressant that has slightly different actions, may also be helpful for RLS. These agents are not addictive and do not have the severe side effects of other RLS drugs, but more research is warranted to determine if they are useful.

Clonidine. Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients and may be an apt choice for patients who have RLS accompanied by hypertension. It also appears to be helpful for RLS patients who are undergoing hemodialysis.

Baclofen. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity of RLS (although not frequency of movements).

WHERE ELSE CAN HELP FOR LEG DISORDERS BE OBTAINED?

American Academy of Sleep Medicine (www.aasmnet.org ). Call 708-492-0930.

National Sleep Foundation (www.sleepfoundation.org ). Call 202-347-3471.

National Center on Sleep Disorders Research (www.nhlbi.nih.gov/about/ncsdr/index.htm ). Call 301-435-0199.

Restless Legs Syndrome Foundation (www.rls.org). Call 877-463-6757.

Worldwide Education and Awareness for Movement Disorders (www.wemove.org ). Call 800-437-6682.

The Movement Disorder Society (www.movementdisorders.org ).

Society for Light Treatment and Biological Rhythms (www.sltbr.org ).

The Sleep Well (www.sleepquest.com ).

Sleep Research Online (www.sro.org ).

A comprehensive website on sleep disorders is available at www.sleephomepages.org.

Review Date: 9/30/2003

Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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