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Restless legs syndrome and related disorders

Highlights

Overview

RLS and PLMD

Treatment

Criteria and Guidelines

Introduction

Restless legs syndrome (RLS) is a poorly understood movement disorder that affects 3 to 15% of the general population. The problem can occur in both children and adults. Although effective treatments are available, RLS often goes undiagnosed.

Symptoms of RLS. The core symptom of RLS is an irresistible urge to move the legs. Some people describe this symptom as a sense of unease and weariness in the lower leg. The sensations are aggravated by rest and relieved by movement. Specific characteristics of RLS include:

Late-onset and Early-onset forms

Restless Legs Syndrome can be either an early-onset or late-onset form of the syndrome. Each form may have different characteristics:

Periodic Limb Movement Disorder

Periodic limb movement disorder (PLMD) is also known as nocturnal myoclonus. Characteristics of PLMD include:

While treatments for the two conditions are similar, PLMD is a separate syndrome. PLMD is also very common in narcolepsy, a sleep disorder that causes people to fall asleep suddenly and uncontrollably.

Causes

The main cause of RLS is unknown. Scientists are researching nervous system problems that may arise in either the spinal cord or the brain. One theory suggests that low levels of the brain chemical dopamine causes RLS.

RLS may often have a genetic basis, particularly in those who develop it before age 40. RLS in older adults is less likely to be inherited.

Central nervous system and peripheral nervous system

The central nervous system includes the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

Genetic Factors

People with RLS often have a family history of the disorder. There are at least six genetic factors that may play a part. Two of the genes are linked to spinal cord development. However, more research is needed to show a link between these genetic factors and dopamine or iron-regulating systems.

Neurological Abnormalities

Dopamine and Neurologic Abnormalities in the Brain

Several studies support the theory that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine, may play a part in RLS. Dopamine triggers numerous nerve impulses that affect muscle movement. The effect is similar to that seen in Parkinson disease. In addition, drugs that increase dopamine levels treat both disorders. However, Parkinson disease itself does not seem to increase the risk for RLS and RLS early in life does not increase the risk of Parkinson later on.

Neurologic Abnormalities in the Spine

Other research suggests that RLS may be due to nerve impairment in the spinal cord. Researchers had thought that such abnormalities began in nerve pathways in the lower spine. However, some patients with RLS have symptoms in the arms, which indicates that the upper spine may also be involved.

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. So far, there is no evidence to support a cause and effect relationship between neuropathy and RLS.

Abnormalities of Iron Metabolism

Iron deficiency, even at a level too mild to cause anemia, has been linked to RLS in some people. Some research suggests that RLS in some people may be due to a problem with getting iron into cells that regulate dopamine in the brain. Some studies have reported RLS in a quarter to a third of people with low iron levels.

Deficiencies in Cortisol

Other research suggests that low levels of the hormone cortisol in the evening and early night hours may be related to RLS. Low-dose cortisol injections have reduced symptoms in some people.

Causes of Periodic Limb Movement Disorder

The causes of PLMD are not clear. Some research 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.

Risk Factors

RLS may affect 1.5 to 2.7% of the general population. Some studies have shown that it may be much more common. It is more common in women than in men, and in North America and Europe, its frequency increases with age.

An international study showed that 2% of children ages 8 to 17 have RLS symptoms. The majority of children with RLS have a parent with RLS. RLS may be more common than epilepsy and diabetes in children and teens.

Family History

As many as two-thirds of people with RLS have a family history of the disorder, and are more likely to develop RLS before they turn 40. People who develop the condition at a later age are less likely to have a family history of RLS. RLS is also more common in people from northern and western Europe, adding support for the theory that some cases have a genetic basis.

Attention Deficit Hyperactivity Disorder

Up to a quarter of children diagnosed with attention-deficit hyperactivity disorder (ADHD) may also have RLS, sleep apnea, and PLMD. These conditions 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. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine.

Pregnancy

About 1 in 5 pregnant women report having RLS. The condition usually goes away within a month of delivery. RLS in pregnancy has been linked to deficiencies in iron and the B vitamin folate.

Dialysis

RLS is relatively common in people undergoing kidney dialysis. Up to two-thirds of patients report this problem. Symptoms often disappear after a kidney transplant.

Anxiety Disorders

Anxiety can cause restlessness and agitation at night. These symptoms can cause RLS or strongly resemble the condition.

Other Conditions Associated with Restless Legs Syndrome

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

Osteoarthritis

Osteoarthritis is a chronic disease of the joint cartilage and bone, once thought to result from "wear and tear" on a joint, although there are other causes such as trauma, and metabolic disorders. Joints appear swollen, are stiff and painful, and usually feel worse the more they are used throughout the day.

Hypothyroidism

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Fibromyalgia

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Rheumatoid arthritis

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Emphysema

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Environmental and Dietary Factors

The following environmental and dietary factors can trigger or worsen RLS:

Medications

Drugs that may worsen or provoke RLS include:

Risk Factors for Periodic Limb Movement Disorder

About 6% of the general population has PLMD. However, the prevalence in older adults is much higher, reaching almost 60%. Studies suggest that PLMD may be especially common in elderly women. As with RLS, there are many conditions that are associated with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and diseases that destroy nerves or the brain over time. Certain drugs, including some antidepressants and anti-seizure medications, may also contribute to PLMD.

Complications

RLS rarely results in any serious consequences. However, recurring severe symptoms may cause considerable mental distress, loss of sleep, and daytime sleepiness. Because the condition is worse while resting, people with severe RLS may avoid activities that involve extended periods of sitting, such as attending movies or traveling long distances.

Sleep Deprivation

Inability to sleep during the night due to RLS symptoms and subsequent daytime sleepiness can cause mood changes. Lack of sleep can also contribute to workplace errors and car crashes.

Effect on Daily Performance and Activities

Sleeplessness has a negative effect on the ability to function while awake. Areas that can be affected include:

Psychiatric Effects

People with RLS are more apt to suffer problems such as social isolation, frequent daytime headaches, and depression. They may also complain of lower sex drive and other problems related to insufficient sleep.

RLS can contribute to insomnia. Insomnia itself can increase the activity of hormones and pathways in the brain that produce emotional problems. Even modest changes in waking and sleeping patterns can have significant effects on a person's mood. In some cases, ongoing insomnia may even predict mood disorders in the future.

It is not clear if RLS is responsible for mood problems or if anxiety or depression contributes to RLS. Anxiety can cause agitation and leg restlessness that resemble RLS. Depression and RLS symptoms also overlap. Certain types of antidepressant drugs, such as serotonin reuptake inhibitors, can increase periodic limb movements during sleep. Medicines used to treat RLS can cause or increase existing psychiatric conditions. Dopamine agonists, for example, can increase compulsive behaviors, such as gambling.

Diagnosis

A diagnosis of RLS often relies mainly on the patient's description of symptoms. The first step in diagnosis is usually to gather information on a person's sleep and personal history. The doctor may ask the following questions:

Keeping a Record of Sleep

To help answer these questions, the patient may need to keep a sleep diary for 2 weeks. The patient should record all sleep-related information, including responses to the questions listed above on a daily basis. Using an extended-play audio or videotape to record sleep behavior can be very helpful in diagnosing sleep apnea. A bed partner can help provide information based on observations of the patient's sleep behavior.

The International Restless Legs Syndrome Study Group (IRLSSG) have updated and simplified diagnostic criteria for pediatric RLS. The criteria stress the understanding of specific words used by children in describing pain.

Sleep Disorders Centers

Some patients may need to consult a sleep specialist or go to a sleep disorders center in order for the problem to be diagnosed. At most centers, patients undergo in-depth testing supervised by a team of consultants from various specialties, who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine.

Signs that may indicate the need to go to a sleep disorders center are:

Polysomnography

Overnight polysomnography involves a series of tests to measure different functions during sleep. This type of evaluation is typically performed in a sleep center. It can help rule out sleep apnea when this problem is suspected or evaluate the effectiveness of RLS treatments.

To undergo the test, the patient arrives about 2 hours before bedtime without having made any changes in daily habits. This test electronically monitors the patient through the various sleep stages. Polysomnography tracks the following:

Actigraphy

Actigraphy uses a small wristwatch-like device (such as Actiwatch) worn on the wrist or ankle. The device monitors the sleep quality in people suspected of having RLS, PLMD, insomnia, sleep apnea, and other sleep-related conditions. It measures and records muscle movements during sleep. For example, with PLMD, actigraphy can provide information on how long movements last and the number of times they occur. It can also track whether PLMD occurs in both legs at the same time, and the effect it has on sleep. Actigraphy is not as accurate as polysomnography because it cannot measure all the biological 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.

The Epworth Sleepiness Scale

SituationChance of Dosing

Sitting and reading

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Watching TV

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting inactive in a public place

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Riding as a passenger in a car for an hour without a break

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Lying down to rest in the afternoon when circumstances permit

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting and talking to someone

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting quietly after a lunch without alcohol

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Sitting in a car while stopped for a few minutes in traffic

(Indicate a score of 0 to 3)

0 = no chance of dozing

1= slight chance of dozing

2 = moderate chance of dozing

3 = high chance of dozing

Score Results

1 to 6: Getting enough sleep.

4 to 8: Tends to be sleepy but is average.

9 and over: Very sleepy and suggestive of sleep-disordered breathing. Patient should seek medical advice.

Diagnosing Iron Deficiency Anemia and Its Causes

Because of the high association between RLS and iron deficiency, a test for low iron stores should be part of the diagnostic workup in RLS. There are two steps in making this diagnosis:

Determining if Iron Stores are Low

The following can help determine if a person is iron deficient:

Other Laboratory Tests

The following laboratory tests may be helpful in determining causes of RLS or identifying conditions that rule it out.

Ruling Out Other Leg Disorders

In addition to other sleep-related leg disorders, many other medical conditions may have features that resemble RLS. The doctor will need to consider these disorders in making a diagnosis.

Peripheral Neuropathies

Peripheral neuropathies are nerve disorders in the hands or feet, which can produce pain, burning, tingling, or shooting sensations in the arms and legs. Several conditions can cause these disorders; diabetes is a very common cause of painful peripheral neuropathies. Other causes include alcoholism, chemotherapy, rheumatoid arthritis, systemic lupus erythematosus, amyloidosis, HIV infection, kidney failure, and certain vitamin deficiencies. Symptoms of peripheral neuropathies may mimic RLS. However, unlike RLS, these disorders are not usually associated with restlessness. Also, movement does not relieve the discomfort, and the problem does not worsen at bedtime.

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 only when the patient is sitting -- not lying down. Drugs that are used to treat nausea, schizophrenia and other psychoses can cause akathisia. The condition also occurs when drugs to treat Parkinson disease are stopped.

Painful Legs and Moving Toes Syndrome

This is a rare disorder that affects 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. The problem gets worse with activity and usually stops during sleep. Most of the time, the cause is unknown, although it may arise from spinal injuries or herpes zoster infection. The condition is difficult to treat, but the drug baclofen, combined with either clonazepam or carbamazepine, has shown some success. Other treatments that may help include orthotic shoe inserts and therapy using transcutaneous electrical nerve stimulation (TENS).

Meralgia Paresthetica

An uncommon nerve condition, meralgia paresthetica causes numbness, pain, tingling, or burning on the front and side of the thigh. It usually occurs on one side of the body. The condition may be caused by compression of the thigh nerve as it passes through the pelvis. The problem typically occurs in those with diabetes, obesity or both, and can affect people of all ages. It often goes away on its own.

Nocturnal (Nighttime) Leg Cramps

Cramps that awaken people during sleep are very common, but they are not RLC or PLMD. Nocturnal leg cramps can be very painful and may cause the person to 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.

What Are Nocturnal Leg Cramps?

Benign nocturnal leg cramps (charley horse) are muscle spasms in the calf. They can occur one or many times during the night. Cramping may also occur in the soles of the feet. Typically, cramps last from a few seconds to a few minutes. Some people experience them regularly, others rarely.

Causes of Nocturnal Leg Cramps

In most cases, the cause of nocturnal leg cramps remains unknown. Among the conditions that might cause leg cramps are:

Individuals at Higher Risk for Nocturnal Leg Cramps

Nocturnal leg cramps occur at all ages but peak at different times. They are particularly common in adolescence, during pregnancy, and in older age, affecting up to 70% of adults over age 50 at some point.

Pregnant women and those taking diuretics are also at risk for leg cramps because of low calcium levels and an imbalance in calcium and phosphorus.

Consequences of Nocturnal Leg Cramps. Nocturnal leg cramps rarely have serious consequences. However, they can be extremely painful and long lasting. Severe symptoms that occur often can cause chronic insomnia and considerable mental distress.

Managing Nocturnal Leg Cramps

Ways to relieve a cramp once it has begun include:

If soreness persists, a warm bath or shower or an ice pack may bring relief.

Lifestyle Tips for Preventing Nocturnal Leg Cramps

Nighttime leg cramps are generally treated with lifestyle changes.

Quinine

Quinine had been widely used to prevent leg cramping. The U.S. Food and Drug Administration (FDA) banned its sale over the counter because it reportedly caused some serious, although rare, side effects. These side effects include bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rashes.

The FDA has since banned the marketing of most quinine drugs, cautioning against the off-label (non-approved) use of the drug to treat nocturnal leg cramps. Only one form of the drug, Qualaquin, is approved for sale. It is used for the treatment of some types of malaria. Pregnant women and people with liver problems should avoid quinine in any form. The FDA has issued a warning of serious, potentially life-threatening side effects resulting from the use of Qualaquin for nocturnal leg cramps. These side effects include dangerously low blood platelet counts (platelets help the blood clot) and permanent kidney damage.

Supplements

Some small studies indicate that the mineral magnesium, taken as magnesium citrate or magnesium lactate, may provide some benefit to people with leg cramps, including pregnant women. Supplements tried for leg cramps include vitamin B complex, vitamin E, calcium, and potassium or sodium chloride, but these do not appear to be very effective. Other drugs that may help include diltiazem (a calcium channel blocker) and naftidrofuryl (unavailable in the United States).

Treatment

Treatment for complaints of sleeplessness and RLS focus on improving sleep and eliminating possible causes of RLS. Initially, doctors normally try to achieve these goals without the use of drugs. A non-drug approach is a particularly important first step for elderly patients.

If the cause cannot be determined, measures to improve sleep habits and relaxation techniques are the best first steps. These approaches may help, even if medicines may be needed later on.

Lifestyle Changes

Some people report that making the following changes help control RLS:

Some patients have tried alternative treatments for RLS, such as acupuncture and massage. To date, however, there is not enough data on the effectiveness of these treatments.

Dietary Iron

RLS is associated with iron deficiency, so people with the condition should make sure they get enough iron in their diet. [For more information, see In-Depth Report #57: Anemia.] Iron is found in foods either in the form of heme or non-heme iron:

Iron Supplements

Iron supplements may reduce symptoms in people with RLS who are also iron deficient. Patients should use them only when dietary measures have failed. Iron supplements do not appear to be useful for RLS patients with normal or above normal iron levels.

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, Ferro-Sequels, 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.

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, 3 times a day.

IMPORTANT:As few as 3 adult iron tablets can poison, and even kill, children. This includes any form of iron pill. No one, not even adults, should take a double dose of iron if they miss one dose.

Tips for taking iron are:

Side Effects

Common side effects of iron supplements include the following:

Interactions With Other Drugs. Certain medicines, including antacids, can reduce iron absorption.

Iron tablets may also reduce the effectiveness of other drugs, including:

At least 2 hours should pass between doses of these drugs and doses of iron supplements.

[For additional information about iron supplements see In-Depth Report #57: Anemia.]

Exercise

Exercise early in the day helps achieve healthy sleep. Vigorous exercise too close to bedtime (1 to 2 hours before) may worsen RLS. A study found that people who walked briskly for 30 minutes, 4 times a week, improved minor sleep disturbances after 4 months. Regular, moderate exercise may help prevent RLS. However, patients report that either bursts of excessive energy or long sedentary periods can worsen symptoms.

Medications

The American Academy of Sleep Medicine recommends medications for RLS or PLMD only for persons who fit within strict diagnostic criteria, and who experience excessive daytime sleepiness as a result of these conditions. Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms. Adverse effects are common and may be troublesome enough to prompt some patients to discontinue their RLS medications.

More research and physician training is needed to better diagnose and treat RLS with medications in children and adolescents. Little is known about the best way to treat RLS in general, but some experts suggest the following for adults:

Tylenol and Non-Steroidal Anti-Inflammatory Drugs

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

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers, bleeding, and possible heart problems. The FDA has asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for heart-related problems and digestive tract bleeding.

Levodopa and Other Dopaminergic Drugs

Dopaminergic drugs increase the availability of the chemical messenger dopamine in the brain, and are the first-line treatment for severe RLS and PLMD. These drugs reduce the number of limb movements per hour, and improve the subjective quality of sleep. Patients with either condition who take these drugs have experienced up to 100% reduction in symptoms.

Dopaminergic drugs, however, can have severe side effects (they are ordinarily used for Parkinson disease). They do not appear to be as helpful for RLS related to dialysis as they do for RLS from other causes.

Dopaminergic drugs include dopamine precursors and dopamine receptor agonists.

Dopamine Precursors

The dopamine precursor levodopa (L-dopa) was once a popular drug for severe RLS, although today it is usually recommended only for patients with occasional symptoms who may take it nightly as needed. It may also be helpful for long car rides or plane trips. 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. Sinemet is commonly prescribed in America. Levodopa combinations are well tolerated and safe.

Levodopa acts fast, and the treatment is usually effective within the first few days of therapy.

Unfortunately, many studies report that patients suffer from augmentation (called augmentation) that occur earlier in the day in up to 70% of patients who take L-dopa. The risk is highest for patients who take daily doses, especially doses at high levels (greater than 200 mg/day). For this reason, patients should use L-dopa fewer than 3 times per week. The drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.

A rebound effect (return of symptoms after the drug is discontinued) causes increased leg movements at night or in the morning as the dose wears off, or as tolerance to the drug builds up.

Regimens

The effects of L-dopa are apparent in 15 to 30 minutes. Dopamine receptor agonists, meanwhile, take at least 2 hours to start working. Some doctors 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 dopaminergic 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. In rare cases, dopaminergic drugs can cause hallucinations or lung disease.

Because these drugs may cause daytime drowsiness, patients should be extremely careful while driving or performing tasks that require concentration.

Long-term use of dopaminergic drugs can lead to tolerance, in which the drugs become less effective.

Rebound effect, augmentation, and tolerance can reduce the value of dopaminergic drugs in the treatment of RLS. Using the lowest dose possible can minimize these effects.

Withdrawal Symptoms

Patients who withdraw from these drugs typically experience severe RLS symptoms for the first 2 days after stopping. RLS eventually returns to pre-treatment levels after about a week. The longer a patient uses these drugs, the worse their withdrawal symptoms.

Withdrawal from dopamine precursors or dopamine agonists can lead to a serious, potentially life-threatening condition called Neuroleptic Malignant Syndrome. This disorder causes muscle stiffness and breakdown, fever, rigidity and confusion. One should never abruptly stop these medications with out first talking to their doctor.

Dopamine Receptor Agonists

Dopamine receptor agonists (also called dopamine agonists) mimic the effects of dopamine by acting on dopamine receptors in the brain. They are now generally preferred to L-dopa (see below). Because they have fewer side effects than L-dopa, including rebound effect and augmentation, these drugs may be used on a daily basis. As the newer drugs are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa.

Because they take longer to take effect, these drugs are not as useful to relieve symptoms once they have begun.

Dopamine agonists have been shown to relieve symptoms in 70% or more of patients.

Other Dopamine Agonists

Other dopamine agonists that have tested in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal). However, there is not enough evidence to support their use for RLS treatment.

Benzodiazepines

Benzodiazepines, such as clonazepam (Klonopin), are known as sedative hypnotics. Doctors prescribe them for insomnia and anxiety. They may be helpful for RLS that disrupts sleep, especially in younger patients. Clonazepam may be particularly helpful for children with both PLMD and symptoms of attention deficit hyperactivity disorder. The medicine also may be helpful for patients with RLS who are undergoing dialysis.

Side Effects

Elderly people are more susceptible to side effects. They 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-acting or short-acting.

Interactions

Benzodiazepines are potentially dangerous when used in combination with alcohol. Some drugs, such as the ulcer medication cimetidine, can slow the breakdown of benzodiazepine.

Withdrawal Symptoms

Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 to 3 weeks after stopping the drug and may include:

Rebound Insomnia

Rebound insomnia, which often occurs after withdrawal, typically includes 1 to 2 nights of sleep disturbance, daytime sleepiness, and anxiety. The chances of rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Narcotic Pain Relievers

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

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

Although the use of narcotics for severe RLS is controversial, some studies have suggested that even when the treatments are long-term, they are rarely addictive for pain sufferers except among patients with a history of substance abuse.

The use of such drugs 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 regularly monitoring those who are taking narcotics. Doses should be adjusted 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. Sleep apnea may worsen symptoms of RLS, insomnia, and other complaints.

Tramadol

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, there are reports of dependence and abuse with this drug as well. Withdrawal after long-term use (longer than a year) can cause intense symptoms, including diarrhea, insomnia, and even RLS itself.

Antiseizure Drugs

Antiseizure drugs, such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol) are being tested for RLS. Common side effects included mild sleepiness and dizziness.

Side Effects

All antiseizure drugs have potentially severe side effects. Therefore, patients should try these medications only after non-drug methods have failed. Side effects of many anti-seizure drugs include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and hair loss. Taking zinc and selenium supplements may help reduce this last effect. Some anti-seizure drugs 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 Drugs

Antidepressants. Bupropion (Wellbutrin), a newer antidepressant, may be helpful for RLS. Bupropion is a weak dopamine reuptake inhibitor, it causes a slight increase in the availability of dopamine in the brain. The drug is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine if it is useful.

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

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

Pregabalin. Pregabalin (Lyrica) is approved for the treatment of diabetic neuropathy, postherpetic neuralgia, and fibromyalgia, and may also be helpful in the treatment of RLS.

Resources

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Review Date: 3/9/2016
Reviewed By: Joseph V. Campellone, MD, Division of Neurology, Cooper University Hospital, Camden, NJ. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.
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