Introduction To RLS

Introduction to RLS
History
The term Restless Leg Syndrome was coined by Professor Karl-Axel
Ekbom in 1944 and is therefore also known as "Ekbom's disease". Ekbom
studied medicine at the Karolinska Institute and later became the first
Professor and head of the department of neurology at Uppsala university
hospital. In his 1945 publication entitled "Restless Legs", Ekbom
described the disease and presented eight cases.
Ekbom was not the first to describe the disease. The earliest
documentation was appears to be by Thomas Willis, a 17th century
English physician of Charles II. Willis studied at the private school of
Edward Sylvester in Oxford and is probably most famous for his
publication Cerebri anatome, published in 1664, a foundational text on
the anatomy of the cerebral system. This book was the first to describe
the term reflex action and the Circle of Willis was outlined and
understood.
In 1672 described what may have been RLS. Willis wrote in a chapter
entitled "Instructions for curing the Watching evil":
.......Wherefore to some, when being in bed they betake
themselves to sleep, presently in the arms and legs. Leaping and
contractions of the tendons and so great a restlessness and
tossing of the members ensure, that the diseased are no more
able to sleep, than if they were in the place of the greatest
torture!....
Willis went on to think that the diseases originated in the spinal cord and
was a product of spinal irritation and used opiates as his therapy of
choice.
Sometimes since I was advised with for a lady of quality, who in
the night was hindered from sleep by reason of these spasmodic
effects which came upon her only twice a week; she took
afterward daily for almost three months, receiving no injury
thereby, either on the brain or about any other function, and when
while by the use of other remedies; the dyscrasia of the blood and
nervous juice being corrected, the animal spirits became more
benign and mild. She afterward leaving wholly the opium was able
to sleep indifferently well!!
What is restless legs?

Restless legs syndrome (RLS) is a neurological disorder with unpleasant
sensations in the legs and an uncontrollable urge to move when at rest to
try to relieve these feelings. RLS sensations are often described by people
as burning, creeping, tugging, or like insects crawling inside the legs, and
a wide variety of descriptions is included in diagnostic criteria. Often
called paresthesias (abnormal sensations) or dysesthesias (unpleasant
abnormal sensations), the sensations range in severity from
uncomfortable to irritating to painful.
Lying down and trying to relax activates the symptoms or makes them
worse. Most people with RLS have difficulty falling asleep and staying
asleep. People are exhausted with daytime fatigue and sleepiness. Many
people with RLS report that job, personal relations, and activities of daily
living are strongly affected as a result of this exhaustion, because they
are unable to concentrate, or have impaired memory.
RLS probably affects 5-10% of people, but may be underdiagnosed and,
in some cases, misdiagnosed. Some people with RLS will not seek medical
attention, believing that they will not be taken seriously, that their
symptoms are too mild, or that their condition is not treatable. Some
physicians wrongly attribute the symptoms to nervousness, insomnia,
stress, arthritis, muscle cramps, or aging.
RLS occurs in women and men, probably slightly more often in women.
Although the syndrome may begin at any age, even as early as infancy,
most patients who are severely affected are middle-aged or older. In
addition, severity appears to increase with age. Older patients experience
symptoms more frequently and for longer.
Most people with RLS also experience a more common condition known as
periodic limb movement disorder (PLMD). PLMD is involuntary leg
twitching or jerking movements during sleep that typically occur every 10
to 60 seconds, in periods or throughout the night. The symptoms cause
repeated awakening and disrupted sleep. Unlike RLS, the movements
caused by PLMD are involuntary-people have no control over them.
Although many patients with RLS also develop PLMD, most people with
PLMD do not experience RLS. Like RLS, the cause of PLMD is unknown.
What are the symptoms of restless legs?

People with RLS feel uncomfortable sensations in their legs, especially
when sitting or lying down, often more in the evening than the day, with
an irresistible urge to move about. Although the sensations can occur on
just one side of the body, most often they affect both sides.
Because moving the legs (or other affected parts of the body) relieves the
discomfort, people with RLS often keep their legs moving to reduce the
unpleasant sensations. They may pace the floor, constantly move their
legs while sitting, and toss and turn in bed.
Most people find the symptoms to be less noticeable during the day and
more pronounced in the evening or at night, especially going to sleep. For
many people, the symptoms disappear by early morning, allowing for
more refreshing sleep at that time. Other triggering situations are periods
of inactivity such as long journeys, or other behaviours that reduce
movement.
The symptoms of RLS vary in severity and duration from person to
person. Mild RLS occurs episodically, with only mild disruption of sleep
onset, and causes little distress. In moderately severe cases, symptoms
occur only once or twice a week but result in significant delay of sleep
onset, with some disruption of daytime function. In severe cases of RLS,
the symptoms occur more than twice a week and result in burdensome
interruption of sleep and impairment of daytime function. There is a
standard symptom scoring system.
What causes RLS?

In most cases, the cause of RLS is unknown (and then doctors call it
idiopathic RLS). Family history of the condition is common, perhaps in half
the sufferers. People with familial RLS tend to be younger when
symptoms start and have a slower progression of the condition.
In other cases, RLS appears to be related to the following factors or
conditions, although researchers do not yet know if these factors actually
cause RLS.
People with low iron levels or anaemia may be prone to developing

RLS. Once iron levels or anaemia is corrected, patients may see a
reduction in symptoms.
Chronic diseases such as kidney failure, diabetes, Parkinson's

disease, and peripheral neuropathy are associated with RLS.
Treating the underlying condition often provides relief from RLS
symptoms.
Some pregnant women experience RLS, especially in their last

trimester. For most of these women, symptoms usually disappear
within four weeks after delivery.
Certain medications-such as antinausea drugs (prochlorperazine or

metoclopramide), antiseizure drugs (phenytoin or droperidol),
antipsychotic drugs (haloperidol or phenothiazine derivatives), and
some cold and allergy medications-may aggravate symptoms.
Patients can talk with their physicians about the possibility of
changing medications.
How is RLS diagnosed?

Currently, there is no single diagnostic test for RLS. The disorder is
diagnosed clinically by evaluating the patient's history and symptoms. In
1995, the International Restless Legs Syndrome Study Group identified
four basic criteria for diagnosing RLS:
1. a desire to move the limbs, often associated with paresthesias or

dysesthesias,
2. symptoms that are worse or present only during rest and are
partially or temporarily relieved by activity,
3. motor restlessness, and
4. nocturnal worsening of symptoms.
A 10-question scoring system is available for RLS diagnosis and severity
scoring.
A more detailed description of diagnostic criteria in adults, children, and
cognitively impaired adults is available.
How is RLS treated?

Relief on movement is generally only temporary. However, RLS can be
controlled by finding any possible underlying disorder. Often, treating the
associated medical condition, like anaemia, peripheral neuropathy or
diabetes, will alleviate many symptoms. For patients with idiopathic RLS,
treatment is directed toward relieving symptoms.
For those with mild to moderate symptoms, prevention is key, and many
physicians suggest certain lifestyle changes and activities to reduce or
eliminate symptoms. Decreased use of caffeine, alcohol, and tobacco may
provide some relief. Doctors may suggest the use of supplements to
correct deficiencies in iron, folate, and magnesium. Studies also have
shown that maintaining a regular sleep pattern can reduce symptoms.
Some individuals, finding that RLS symptoms are lower in the early
morning, change their sleep patterns. Others have found that a program
of regular moderate exercise helps them sleep better. Taking a hot bath,
massaging the legs, or using a heating pad or ice pack can help relieve
symptoms in some patients. Although many patients find some relief with
such measures, rarely do these efforts completely eliminate symptoms,
and for many of these measures there is only anecdotal evidence that
they work.
A variety of drugs have been tried, often not in large or long trials. Some
seem to work well in reducing periodic leg movements, or daytime
tiredness, or improving sleep, or reducing RLS symptom severity, but
there is no magic bullet as yet.
http://www.medicine.ox.ac.uk/bandolier/booth/RLS/RLSintro.html
Restless legs syndrome and related

disorders
Description
An in-depth report on the causes, diagnosis, treatment, and
prevention of RLS.
Alternative Names
Ekbom's syndrome
Highlights
Overview
Restless leg syndrome (RLS) can be a temporary problem (such as during pregnancy) or a
chronic, long-term issue. It can develop from several medical conditions and genetic risk factors.
The condition involves a feeling of "pulling, searing, drawing, tingling, bubbling, or crawling"
beneath the skin, usually in the calf area. This causes an irresistible urge to move the legs. These
sensations can sometimes
affect the thighs, feet, and sometimes even the arms. Treatment often includes over-the-counter
remedies and lifestyle changes. Iron supplements may be recommended in cases where a lack of
iron has been identified. Prescription medications can provide good relief of symptoms.
RLS and PLMD:
Periodic limb movement disorder (PLMD) is a condition where leg muscles contract and jerk
every 20 - 40 seconds during sleep. These movements may last less than 1 second, or as long as
10 seconds.
Unlike RLS, contractions in PLMD usually do not wake patients.
Four out of five people who have of RLS sufferers also report having PLMD, but only about a
third of people with PLMD also have RLS.
New Treatment:
An antiseizure agent, gabapentin enacarbil (Horizant), was approved by the Food and Drug
Administration (FDA) in 2011 for moderate-to-severe RLS. Common side effects included mild
sleepiness and dizziness.
The drug rotigotine (Neupro) was withdrawn from the US in 2008 because of concerns about
absorption of the medication from the skin patch. The issue has since been corrected and the drug
was approved in April 2012 for treatment of moderate-to-severe RLS.
Introduction
Restless legs syndrome (RLS) is a poorly understood movement
disorder that affects 3 - 15% of the general population. The
problem can occur in both children and adults. Although effective
treatments are available, RLS often goes undiagnosed.
The core symptom of RLS is an irresistible urge to
move the legs (medically known as akathisia). 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:
Symptoms of RLS.
"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 mostly in the lower
legs, but they can sometimes affect the thighs, feet, and even the upper body. RLS-type symptoms
may also occur in the arms. These may be the first symptoms of RLS in some people.
About 4 out of 5 patients with RLS also have semi-rhythmic movements during sleep, a
condition called periodic limb movement disorder (PLMD). (See description below.)
Itching and pain, particularly aching pain, may be present.
Patients experience symptoms when they feel most relaxed and their legs are at rest.
Symptoms usually occur at night when lying down. In more severe cases,symptoms also occur
during the day while sitting.
Episodes of RLS usually develop between 10 p.m. and 4 a.m. Symptoms are often worse
shortly after midnight and disappear by morning. If the condition becomes more severe, people
may begin to have symptoms during the day, but the problem is always worse at night.
The unpleasant sensations and uncontrollable urge to move the legs often disturbs nighttime
sleep. When the person tries to ignore the urge to move the legs, tension builds up until the legs
jerk uncontrollably. Individuals who experience daytime symptoms may find it difficult to sit during
air or car travel, or through classes or meetings.
There appear to be two forms of RL -early-onset and late-onset. Each form may have different
characteristics:
Late-onset and Early-onset Forms.
People with early-onset RLS (occurring in the teenage years or earlier) tend to have a family
history of the disorder. They usually have RLS without accompanying pain.
People with late-onset RLS usually do not have a family history of RLS. The condition is more
likely to result from a problem with the nervous system. Symptoms may also include pain in the
lower legs.
Periodic Limb Movement Disorder

Periodic limb movement disorder (PLMD) is also known as
nocturnal myoclonus. PLMD symptoms include:
Nighttime episodes that usually peak near midnight (similar to the pattern in restless legs
syndrome).
Contractions and jerking of the leg muscles every 20 - 40 seconds during sleep.
These movements may last less than 1 second, or as long as 10 seconds.
PLMD usually does not wake patients. This condition is distinct from the brief and sudden
movements that occur just as people are falling asleep; these brief jerking movements may
interrupt sleep.
Four out of five people who have RLS also report having PLMD, but only a third of people
with PLMD report having RLS.
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 restless legs syndrome.
RLS may often have a genetic basis, particularly in those who

develop it before age 40. Restless legs syndrome in older adults
is less likely to be inherited.
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.
Researchers have detected at least six genetic factors that may
play a part. Two of the genes are linked to spinal cord
development. Although none of the genes has been associated
with dopamine or iron-regulating systems, these factors are
considered likely causes of the condition.
Neurological Abnormalities
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's disease. In addition, drugs that increase dopamine
levels treat both disorders. However, Parkinson's disease itself
does not seem to increase the risk for RLS and RLS early in life
does not increase the risk of Parkinson's later on.
Dopamine and Neurologic Abnormalities in the Brain.
Other research suggests that restless

legs syndrome 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.
Neurologic Abnormalities in the Spine.
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.
Neuropathy.
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 suggest 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 restless leg
symptoms. 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 3 - 15% of the general population. It is more
common in women than in men, and its frequency increases with
age. The disorder affects an estimated 10 - 28% of adults older
than age 65, however 4 in 10 patients have their first symptoms
of RLS as teenagers.
An international study showed that 2% of children ages 8 - 17

have RLS symptoms. RLS may be more common than epilepsy
and diabetes in children and teens.
Family History
As many as two-thirds of people with restless legs syndrome
(RLS) have a family history of the disorder. In people with a family
history of the condition, RLS is more likely to occur 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

RLS and PLMD in children are strongly associated with
inattention and hyperactivity. 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
Restless legs syndrome 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 restless legs syndrome or strongly
resemble the condition.
Other Conditions Associated with Restless Legs

Syndrome
The following medical conditions are also associated with restless
legs syndrome, although the relationships are not clear. In some
cases, these conditions may contribute to RLS. Others may have
a common cause. In some cases, they may coexist due to other
risk factors:
Osteoarthritis (degenerative joint disease). About three-quarters of patients with RLS also
have osteoarthritis, a common condition affecting older adults.
Varicose veins. Varicose veins occur in about 1 in 7 patients with RLS.
Obesity
Diabetes. People with type 2 diabetes may have higher rates of secondary RLS. Nerve pain
(neuropathy) related to their diabetes cannot fully explain the higher rate of RLS.
Hypertension
Hypothyroidism (a condition in which the thyroid gland does not make enough hormones)
Fibromyalgia (chronic pain of unknown cause)
Rheumatoid arthritis
Emphysema (a lung disease usually caused by smoking)
Chronic alcoholism
Sleep apnea (pauses in breathing during sleep) and snoring
Chronic headaches
Brain or spinal injuries
Many muscle and nerve disorders. Of particular interest is hereditary ataxia, a group of
genetic diseases that affects the central nervous system and causes loss of motor
control. Researchers believe that hereditary ataxia may supply clues to the genetic causes of RLS.
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.
Click the icon to see an image of hypothyroidism.
Click the icon to see an image detailing fibromyalgia.
Click the icon to see an image detailing rheumatoid arthritis.
Click the icon to see an image detailing emphysema.
Environmental and Dietary Factors

Several environmental and dietary factors can trigger or worsen
restless legs syndrome:
Iron deficiencies. People who are deficient in iron are at risk for restless legs syndrome, even
if they do not 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 RLS include:
Antidepressants
Antipsychotic drugs
Anti-nausea drugs
Calcium channel blockers (mostly used to treat high blood pressure)
Metoclopramide (used to treat various digestive diseases)
Antihistamines
Oral decongestants
Diuretics
Asthma drugs
Spinal anesthesia (anesthesia-induced restless legs syndrome typically disappears on its own
within several months)
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 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.
Studies suggest that sleeplessness
has a negative effect on the ability to function while awake. Areas
that can be affected include:
Effect on Daily Performance and Activities.
Concentration. Loss of deep sleep appears to impair the brain's ability to process information.
Task performance. Missing several hours of sleep every night over the course of a week can
negatively affect a person's ability to function. It also affects mood. In fact, people deprived of
sleep show lowered performance levels on a par with those of people who are intoxicated.
Learning. The extent to which sleeplessness impairs learning is unclear. Some studies have
reported problems in memorization. Other studies, however, have found no differences in test
scores between people with temporary sleep loss and those with regular sleep cycles.
Psychiatric Effects
People with restless legs syndrome are more apt to suffer
problems such as social isolation, frequent daytime headaches,
and depression. The 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. In addition, certain types of
antidepressant drugs, such as seratonin reuptake inhibitors, can
increase periodic limb movements during sleep.
Diagnosis
A diagnosis of restless legs syndrome 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:
How would you describe your sleep problem?
How long have you had this sleep problem? How long does it take you to fall asleep?
How many times a week does the problem occur?
How restful is your sleep?
What do your leg problems feel like (such as cramps, twitching, and crawling feelings)?
What is your sleep environment like? Noisy? Not dark enough?
What medications are you taking (including the use of antidepressants and self-medications -such as herbs, alcohol, and over-the-counter or prescription drugs)?
Are you taking or withdrawing from stimulants, such as coffee or tobacco? How much alcohol
do you drink per day?
What stresses or emotional factors may be present in your life? Have you experienced any
significant life changes?
Do you snore or gasp during sleep? (This may be an indication of sleep apnea. Sleep apnea
is a condition in which breathing stops for short periods many times during the night. It may worsen
symptoms of restless legs syndrome or insomnia.)
If you have a bed partner, does he or she notice that you have jerking legs, interrupted
breathing, or thrashing while you sleep?
Are you a shift worker?
Do you have a family history of RLS or periodic movement limb disorder, "growing pains" at
night, or night walking?
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 described 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.
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 for a sleep disorders center are:
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)
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 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.
Polysomnography electronically monitors the patient through the
various sleep stages. Polysomnography tracks the following:
Brain waves
Body movements
Breathing
Heart rate
Eye movements
Changes in breathing and blood levels of oxygen
Actigraphy
Actigraphy uses a small wristwatch-like device (such as
Actiwatch) worn on the wrist or ankle. The device monitors or
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

Situation
Chance of Dosing
(Indicate a score of 0 to 3)
0 = no chance of dozing
Sitting and reading
1= slight chance of dozing

2 = moderate chance of dozing
3 = high chance of dozing
Watching TV

Sitting inactive in a public place

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

break

Lying down to rest in the afternoon when circumstances
permit

Sitting and talking to someone

Sitting quietly after a lunch without alcohol

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

Score Results
1 - 6: Getting enough sleep.
4 - 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 restless legs syndrome
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:
The first step is to determine if a person is actually deficient in iron.

If iron stores are low, the second step is to diagnose the cause of the iron deficiency, which
will help determine treatment.
The following findings are important in

determining that a person is iron deficient:
Determining if Iron Stores are Low:
Blood cells viewed under the microscope are pale (hypochromic) and abnormally small
(microcytic). These observations suggest iron deficiency, but they can appear in anemia resulting
from chronic disease and thalassemia (an inherited blood disorder), as well.
Hemoglobin and iron levels are low. These findings further suggest iron deficiency, but they
can also occur in cases of anemia due to chronic disease. Ferritin levels are low.
Ferritin is a protein that binds to iron; low levels typically indicate a lack of iron in the body.
However, normal levels of ferritin in the blood do not always mean a patient has enough iron. For
example, pregnant women in their third trimester or patients with a chronic disease may not have
enough iron even with normal or high ferritin levels.
A test that measures a factor called serum transferrin receptor (TfR) is proving to be very
sensitive in identifying iron deficiency in some patients, including the elderly with chronic diseases
and possibly pregnant women. When iron deficiency anemia is diagnosed, the next step is to
determine the cause of the iron deficiency itself. Menstrual blood loss is a common cause of iron
deficiencyin women of reproductive age. Tests to check for an underlying cause of iron deficiency,
such as gastrointestinal (digestive tract) bleeding, are particularly important in men,
postmenopausal women, and children. [See In-Depth Report #57: Anemia.]
Other Laboratory Tests

The following laboratory tests may be helpful in determining
causes of restless legs syndrome (RLS) or identifying conditions
that rule it out.
Blood glucose tests for diabetes
Tests for kidney problems
In certain cases, tests for thyroid hormone, magnesium, and folate levels
Electromyography (recording the electrical activity of muscles) for neuropathy, radiculopathy

(problem with the nerve roots), myelopathy (problem with the spinal cord)
Central nervous system MRI for myelopathy or stroke
Ruling Out Other Leg Disorders

In addition to other sleep-related leg disorders, many other
medical conditions may have features that resemble restless legs
syndrome (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,
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 ar not usually associated with
restlessness. Also, movement does not relieve the discomfort,
and the 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. Also, it usually

happens only when the patient is sitting -- not lying down. Antinausea drugs and drugs used to treat schizophrenia and other
psychoses can cause akathisia. The condition also occurs when
drugs to treat Parkinson's 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
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 people aged 30 to 60 years, but it 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 part of restless legs syndrome or periodic limb
movement disorder. Nocturnal leg cramps can be very painful
and may cause the 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.
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:
Calcium and phosphorus imbalances, particularly during pregnancy
Low potassium or sodium levels
Overexertion, standing on hard surfaces for long periods, or prolonged sitting (especially with
the legs contorted)
Having structural disorders in the legs or feet (such as flat feet)
Medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia,
hypoglycemia, anemia, and certain medications. Various diseases that affect nerves and muscles,
such as Parkinson's, cause leg cramps. Peripheral neuropathy, a complication of diabetes, can
cause cramp-like pain, numbness, or tingling in the legs. Patients with kidney disease undergoing
dialysis are also prone to leg cramps.
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, like restless

legs syndrome, 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:
Straightening the leg, flexing the foot upward toward the knee, or grabbing the toes and
pulling them toward the knee.
Walking, or shaking the affected leg then elevating it.
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.
People with leg cramps should drink plenty of water (at least 6 to 8 glasses daily) to maintain
adequate fluid levels. Nightly stretching exercises may help prevent leg cramps from occuring.
(This are generally recommended for RLS, as well).
To stretch leg muscles: Stand about 30 inches from a wall. Keeping heels flat on the floor,
lean forward and slowly move hands up the wall to achieve a comfortable stretch.
Alternately, pedal for a few minutes on a stationary bicycle at bedtime.

While in bed, loose covers should be placed over the toes and feet. This prevents the toes
and feet from pointing, which causes calf muscles to contract and cramp. Propping the feet up
higher than the torso may also help.
Regular swimming and water exercises are a good way to keep muscles stretched.
Wearing supportive footwear may help reduce leg cramps
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 (nighttime) 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. In July 2010 the FDA
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. In one small study, taking vitamin B complex
was shown to be helpful. Other supplements tried for leg cramps
include vitamin E, calcium, and potassium or sodium chloride, but
these do not appear to be very effective.
Treatment
Treatment for complaints of sleeplessness and restless legs
syndrome focus on efforts to improve sleep and eliminate
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.
The doctor should first try to treat any underlying medical conditions that may be causing
restless legs.
If medications may be causing RLS, the doctor should try to prescribe alternatives.
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 restless legs syndrome:
Taking hot baths or using cold compresses.
Stopping smoking.
Getting enough exercise during the day.
Doing calf stretching exercises at bedtime.
Using Ergonomic measures. For example, working at a high stool where legs can dangle
helps some people. Also, sitting on a aisle during meetings or airplane travel can allow for more
leg movement.
Changing sleep patterns. Some people report that symptoms do not occur when they sleep in
the late morning. Therefore, patients may consider changing their sleep patterns if feasible.
Avoiding caffeine, alcohol, and nicotine also improves some cases of 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
Restless legs syndrome is associated with iron deficiency, so
people with the condition should 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:
Foods containing heme iron are the best for increasing or maintaining healthy iron levels.
Such foods include clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-heme iron is less well absorbed. Over half the iron in meat is non-heme. Eggs, dairy
products, and iron-containing vegetables (including dried beans and peas) have only the nonheme form. Other sources of non-heme iron include iron-fortified cereals, bread, and pasta
products, dark green leafy vegetables (such as chard, spinach, mustard greens, and kale), dried
fruits, nuts, and seeds.
Iron Supplements
Iron supplements may reduce symptoms in people with restless
legs syndrome 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.
To replace iron, the preferred forms of iron tablets

are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, MolIron). 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.
Supplement Forms.
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.
Regimen.
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:
For best absorption, take iron between meals. (Iron may cause stomach and intestinal
disturbances, however. Some experts believe that you can take low doses of ferrous sulfate with
food and avoid the side effects.)
Always drink a full 8 ounces of fluid with an iron pill.
Keep tablets in a cool place. Bathroom medicine cabinets may be too warm and humid, which
may cause the pills to disintegrate.
Common side effects of iron supplements include the

following:
Side Effects.
Constipation and diarrhea may occur but these side effects are rarely severe. However, iron
tablets can aggravate existing digestive problems such as ulcers and ulcerative colitis.
Nausea and vomiting may occur with high doses. You can control this by taking smaller
amounts. Switching to ferrous gluconate may help some people with severe digestive problems.
Black stools are normal when taking iron tablets. In fact, if stools do not turn black, the tablets
may not be working effectively.
Stools appear tarry or have red streaks may indicate bleeding in the digestive tract, which
may be causing iron deficiency. Other warning signs include cramps, sharp pains, or soreness in
the stomach. Intestinal bleeding requires immediate medical attention.
Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength
tablets.
Certain medicines, including antacids, can

reduce iron absorption.
Interactions With Other Drugs.
Iron tablets may also reduce the effectiveness of other drugs,

including:
Antibiotics -- tetracycline, penicillamine, and ciprofloxacin
Anti-Parkinson's disease drugs -- methyldopa, levodopa, and carbidopa
At least 2 hours should elapse 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
too close to bedtime (1 to 2 hours before) may worsen restless
legs syndrome (RLS). A study found that people who walked
briskly for 30 minutes, four 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.
Pneumatic Compression Device

Small studies have shown that the use of a pneumatic
compression device improves symptoms on RLS in some
patients. Pneumatic compression devices wrap an inflatable cuff
around the legs. This cuff is attached to a device which then
increases pressure around the legs. It is worn for at least an hour,
generally around the time symptoms usually begin.
Medications
The American Academy of Sleep Medicine recommends

medications for RLS or PLMD only for persons who fit 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).
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:
If lifestyle changes do not control the problem, over-the-counter pain relievers should be the
first form of treatment.
People with RLS should have a test for iron deficiency. If they are iron deficient, they should
start treatment with iron supplements.
Dopaminergic drugs (drugs that increase levels of dopamine) are the standard medicines for
treating severe RLS, PLMD, or both.
Other drugs may be helpful if dopaminergic drugs fail, or for patients who have frequent -- but
not nightly -- symptoms. These include opiates (pain relievers), benzodiazepines (sedative
hypnotic drugs), or anticonvulsants. However, benzodiazepines and opiates can become habit
forming and addictive.
Tylenol and Non-Steroidal Anti-Inflammatory

Drugs
Before taking stronger medications, people should try over-thecounter 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).
Although NSAIDs work well, long-term use can cause stomach
problems, such as ulcers, bleeding, and possible heart problems.
In April 2005, the FDA 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 significantly 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's 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 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. About 30% of patients
who take dopamine receptor agonists have reported
augmentations symptoms. 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.
Dopamine Receptor Agonists.
Dopamine agonists have been shown to relieve symptoms in

70 to 90% of patients. Dopamine agonists can be ergot-derived
(such as cabergoline) or non-ergot derived (such as pramipexole
and ropinirole). The newer non-ergotamine derivatives may

induce fewer side effects than ergot-derived drugs:
Ropinirole (Requip) was the first drug approved specifically for treatment of moderate-tosevere RLS (more than 15 RLS episodes a month). Side effects are generally mild but may include
nausea, vomiting, drowsiness, and dizziness.
Pramipexole (Mirapex) is also approved for RLS. However, patients may fall asleep, without
warning, while taking this drug, even while performing activities such as driving.
Rotigotine is a patch preparation. Common side effects include back or joint pain, dizziness,
decreased appetite, dry mouth, fatigue, sweating, trouble sleeping or upset stomach.
Cabergoline is a dopamine agnoist that should be used only when other medications have
been tried and failed; it poses a risk of heart valve damage.
Other dopamine agonists that have shown

some promise in small studies include alpha-dihydroergocryptine,
or DHEC (Almirid), and piribedil (Trivastal).
Other Dopamine Agonists.
The dopamine precursor levodopa (L-dopa) was

once a popular drug for severe RLS. Although it can still be
useful, most doctors now prefer the newer dopamine agonists
(see above). 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 well tolerated and safe.)
Dopamine Precursors.
Patients typically start with a very low dose taken 1 hour before
bedtime. The dosage is increased until the patient finds relief.
Patients sometimes need to take an extended-release form or to
take it again during the night.
Levodopa acts fast, and the treatment is usually effective within
the first few days of therapy.
Serious common side effects of L-dopa treatment (and, to lesser
extent, of dopamine receptor agonists) are augmentation and
rebound. Many studies report that augmentation (worsening of
symptoms that occur earlier in the day) occurs 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 only
intermittently (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.
The rebound effect causes increased leg movements at night or
in the morning as the dose wears off, or as tolerance to the drug
builds up.
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.
Regimens.
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. Adding the drug domperidone may help to
relieve this side effect. In rare cases, dopaminergic drugs can
cause hallucinations or lung disease.
Side Effects.
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 tolerance, which
results in to loss of effectiveness. Adding a drug called
entacapone (Comtan) may prolong the duration of action of
carbidopa-levodopa therapy, but it can cause nausea.
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.
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 Symptoms.
Benzodiazepines
Benzodiazepines, such as clonazepam (Klonopin), are known as
sedative hypnotics. Doctors prescribe them for insomnia and
anxiety. They may be helpful for restless legs syndrome (RLS)
that disrupts sleep, especially in younger patients. Clonazepam
may be particularly helpful for children with both periodic limb
movement disorder and symptoms of attention deficit
hyperactivity disorder. The medicine also may be helpful for
patients with RLS who are undergoing dialysis.
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.
Side Effects.
The drugs may increase depression, a common condition in many people with insomnia.
Breathing problems may occur with overuse or in people with pre-existing respiratory illness.
Long-acting drugs 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.
There are reports of memory loss (so-called traveler's amnesia), sleepwalking, and odd mood
states after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are
rare and probably enhanced by alcohol.
Because benzodiazepines cross the placenta and enter breast milk, pregnant and nursing
women should not use them. There are some reports of an association between the use of
benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns.
Studies are conflicting at this point, but other side effects are known to occur in babies exposed to
these drugs in the uterus.
In rare cases, overdoses have been fatal.
Benzodiazepines are potentially dangerous when used in

combination with alcohol. Some drugs, such as the ulcer
medication cimetidine, can slow the breakdown of
benzodiazepine.
Interactions.
Withdrawal symptoms usually occur after

prolonged use and indicate dependence. They can last 1 to 3
weeks after stopping the drug and may include:
Withdrawal Symptoms.
Gastrointestinal distress
Sweating
Disturbed heart rhythm
In severe cases, patients might hallucinate or experience seizures, even a week or more after
they stop taking the drug.
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.
Rebound Insomnia.
Narcotic Pain Relievers

Narcotics are pain-relieving drugs that act on the central nervous
system. They are sometimes prescribed for severe cases of
restless legs syndrome (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:
Opiates (such as morphine and codeine) come from natural opium. Some patients report
relief with the use of the opiate fentanyl (Duragesic), available in skin patch form. An implanted
pump that uses morphine and an anesthetic called bupivacaine is showing promise for patients
with severe RLS. The pump delivers the drugs to the fluid surrounding the spinal cord
(cerebrospinal fluid).
Opioids are synthetic drugs. The most common example is oxycodone (Percodan, Percocet,
Roxicodone, OxyContin, Methadone, and Hydrocodone).
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 longterm 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 (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 restless legs syndrome itself.
Tramadol.
Antiseizure Drugs
Antiseizure drugs -- such as gabapentin (Neurontin), valproic acid
(valproate, divalproex, Depakote, Depakene), and
carbamazepine (Tegretol) are being tested for restless legs
syndrome (RLS). In 2011 the FDA approved gabapentin
enacarbil, a form of gabapentin, for the once daily treatment of
moderate to severe RLS. Gabapentin enacarbil converts to

gabapentin in the intestines, and therefore may reduce some of
the side effects experienced by patients taking antiseizure
medications. (Common side effects included mild sleepiness and
dizziness.) The drug is marketed under the name Horizant
Extended Release.
All antiseizure drugs have potentially severe side effects.
Therefore, patients should try these medications only after nondrug 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 antiseizure 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.
Side Effects.
Other Drugs
Bupropion (Wellbutrin), a newer antidepressant, may
be helpful for restless legs syndrome (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.
Antidepressants.
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).
Alpha-2 Delta Blockers.
Gabapentin and gabapentin enacarbil appear to

help RLS sufferers. Pregabalin is currently under study.
Resources
www.aasmnet.org -- American Academy of Sleep Medicine
www.sleepfoundation.org -- National Sleep Foundation
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nhlbi.nih.gov/about/ncsdr/ -- National Center on Sleep Disorders Research
www.rls.org -- Restless Legs Syndrome Foundation
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders
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Version Info
Last Reviewed on 01/10/2013

Reviewed by: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard
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https://umm.edu/health/medical/reports/articles/restless-legs-syndrome-andrelated-disorders
Causes of restless legs

syndrome
In many cases, the exact cause of restless
legs syndrome is unknown.
When no cause can be found, it's known as
"idiopathic" or primary restless legs syndrome.
Research has identified specific genes related to
restless legs syndrome, and it can run in families.
In these cases, symptoms usually occur before
the age of 40.
Dopamine
There's evidence to suggest restless legs
syndrome is related to a problem with part of the
brain called the basal ganglia. The basal ganglia
uses a chemical (neurotransmitter) called
dopamine to help control muscle activity
and movement.
Dopamine acts as a messenger between the
brain and nervous system to help the brain
regulate and co-ordinate movement. If nerve cells
become damaged, the amount of dopamine in

the brain is reduced, which causes muscle
spasms and involuntary movements.
Dopamine levels naturally fall towards the end of
the day, which may explain why the symptoms of
restless legs syndrome are often worse in the
evening and during the night.
Underlying health condition

Restless legs syndrome can sometimes occur as
a complication of another health condition, or it
can be the result of another health-related factor.
This is known as secondary restless legs
syndrome.
You can develop secondary restless legs
syndrome if you:
have iron deficiency anaemia low levels of iron in the blood can lead
to a fall in dopamine, triggering restless legs syndrome
have a long-term health condition such as chronic kidney
disease, diabetes, Parkinson's disease, rheumatoid arthritis,
anunderactive thyroid gland, or fibromyalgia
are pregnant particularly from week 27 until birth; in most cases the
symptoms disappear within four weeks of giving birth
Triggers
There are a number of triggers that don't
cause restless legs syndrome, but can make
symptoms worse. These include medications

such as:
some antidepressants
antipsychotics
lithium used in the treatment of bipolar disorder

calcium channel blockers used in the treatment of high blood pressure
some antihistamines
metoclopramide used to relieve nausea
Other possible triggers include:
excessive smoking, caffeine or alcohol

being overweight or obese
stress
lack of exercise
Page last reviewed: 02/09/2015

Next review due: 02/09/2017
http://www.nhs.uk/Conditions/Restless-leg-syndrome/Pages/Causes.aspx
INTRODUCTION Restless legs syndrome/Willis-Ekbom disease (RLS/WED) refers to an

overwhelming urge to move the legs, usually associated with unpleasant sensations. The urge to
move the legs is worse at rest and at night and relieved by movement. RLS/WED is commonly
associated with sleep disturbance and with involuntary, jerking movements of the legs during sleep,
known as periodic leg movements of sleep (PLMS). When significant sleep disturbances or impaired
daytime functioning coexist with PLMS in the absence of RLS/WED or other associated disorders, the
term periodic limb movement disorder (PLMD) is used.
RLS/WED is a treatable condition that generally responds well to pharmacologic therapy. A variety of
treatments have been studied in randomized, controlled trials; the major classes of drugs used include
dopaminergic agents, alpha-2-delta calcium channel ligands, opioids, and benzodiazepines [1-4]. The
treatment approach to PLMD is similar to that of RLS/WED, although supported by considerably less
data. (See 'Periodic limb movement disorder' below.)
The selection of therapy depends upon a number of factors, including disease severity, patient age,
comorbidities (eg, pain, depression, anxiety, history of impulse control behaviors), drug side effects,
and patient preferences. The goals of therapy are to reduce or eliminate symptoms of RLS/WED and
improve daytime function, sleep, and quality of life.
This topic will review the treatment of RLS/WED and PLMD in adults. The clinical features and
diagnosis of RLS/WED and PLMD in adults and treatment of these disorders in children are discussed
separately. (See "Clinical features and diagnosis of restless legs syndrome/Willis-Ekbom disease and
periodic limb movement disorder in adults" and "Restless legs syndrome/Willis-Ekbom disease and
periodic limb movement disorder in children".)
IRON REPLACEMENT A serum ferritin concentration lower than 45 to 50 mcg/L (ng/mL) has been
associated with an increased severity of restless legssyndrome/WillisEkbom disease (RLS/WED), and iron replacement is suggested if the serum ferritin level is lower than
75 mcg/L [5]. Iron therapy should not be prescribed empirically because it may result in iron overload,
especially in patients with previously unsuspected hemochromatosis.
This recommendation is based on evidence supporting a role for iron deficiency in the
pathophysiology of RLS/WED and three small randomized placebo-controlled studies showing a
clinical benefit in patients receiving iron replacement therapy: one in adult patients with serum ferritin
75 mcg/L treated with oral iron [6], one in patients with end-stage renal disease and functional iron
deficiency treated with intravenous iron dextran [7], and a third in patients with moderate to
severe RLS/WEDtreated with intravenous ferric carboxymaltose [8].
Two other randomized studies of intravenous iron sucrose, only one of which was limited to irondeficient patients, failed to show a benefit [9,10]. A meta-analysis that included four out of five of these
studies found significant heterogeneity in the formulation of iron used, patient characteristics, and
measurement of outcome variables across studies and found insufficient evidence to conclude
whether iron is beneficial for treatment of RLS/WED [1].
Iron supplementation can be supplied orally or intravenously. Intravenous delivery has the advantage
of replenishing iron stores more quickly than oral therapy but it is less convenient and carries a risk of
serious infusion reactions, including anaphylaxis. There are no direct comparisons of intravenous
versus oral iron supplementation in patients with RLS/WED, and available data do not show clear
superiority of one route of administration over the other. (See "Treatment of the adult with iron
deficiency anemia", section on 'Prevention and treatment of adverse drug events'.)
Because oral iron is easier to administer and safer, we suggest initial therapy with an oral regimen
such as ferrous sulfate (325 mg orally two to three times a day). Iron should be combined with vitamin
C (100 to 200 mg with each dose of ferrous sulfate) or a glass of orange juice to enhance absorption.
Iron should not be taken at the same time as calcium supplements or significant amounts of dairy
products. (See "Treatment of the adult with iron deficiency anemia".)
Intravenous iron therapy is generally reserved for patients with low iron stores and either a
malabsorption state or complete intolerance to oral iron preparations. (See"Treatment of the adult with
iron deficiency anemia", section on 'Oral iron therapy'.)
Ferritin levels should be checked after three to four months of therapy and then every three to six
months until the serum ferritin level is >75 mcg/L and iron saturation is greater than 20 percent.
Monitoring is important to avoid the rare but serious complication of iron overload in patients with
hemochromatosis genes [11]. Iron therapy can then be discontinued if an ongoing cause for iron
deficiency has not been established. The etiologic evaluation of iron deficiency in adults is reviewed
separately. (See "Causes and diagnosis of iron deficiency anemia in the adult", section on 'Search for
source of blood and iron loss'.)
NONPHARMACOLOGIC THERAPY In patients with mild symptoms, nonpharmacologic therapies

may be sufficient for symptom relief. In patients with more severe symptoms, nonpharmacologic
measures are worth reviewing, as they may limit medication requirements.
Behavioral strategies Use of the following interventions is supported primarily on the basis of
clinical experience and, in some cases, small randomized trials [5,12]:
Mental alerting activities, such as working on a computer or doing crossword puzzles, at times
of rest or boredom
Avoidance of aggravating factors, including consideration of withdrawal of possibly
predisposing medications (see 'Avoidance of aggravating factors' below)
Moderate regular exercise [13]
Reduced caffeine intake
For symptomatic relief walking, bicycling, soaking the affected limbs, and leg massage,
including pneumatic compression [14]
Short daily hemodialysis for patients with end-stage renal disease (see "Sleep disorders in
end-stage renal disease", section on 'Treatment')
Avoidance of aggravating factors Sleep deprivation is known to aggravate symptoms of restless
legs syndrome/Willis-Ekbom disease (RLS/WED) in many patients, and general principles of sleep
hygiene should be reviewed. (See "Treatment of insomnia", section on 'Sleep hygiene'.)
Antidepressants, neuroleptic agents, dopamine-blocking antiemetics such as metoclopramide, and
sedating antihistamines (including those found in nonprescription medications) may contribute to
emergence of RLS/WED or worsening of prior symptoms (table 1) [15]. Most antidepressant classes
have been associated withRLS/WED, including tricyclics, selective serotonin reuptake inhibitors, and
serotonin-norepinephrine reuptake inhibitors [16].
Discontinuation of antidepressants, however, may not always be possible without causing patient
harm. If antidepressants are necessary, the symptoms of secondaryRLS/WED can usually be treated
in the same way as primary RLS/WED. Bupropion is an alternative antidepressant that may be less
likely to induce or worsenRLS/WED [17].
Novel devices A device that provides vibratory stimulation to the legs (Relaxis Pad) was approved
by the US Food and Drug Administration (FDA) in May 2014 for use in patients with RLS/WED. We do
not find compelling evidence of benefit from the available data, however, and we suggest that patients
not use this device until further studies have been performed and reported in peer reviewed
publications.
According to a pooled analysis of two randomized trials (156 patients) published in a non-MEDLINEindexed journal, patients assigned to the vibrating pad experienced improvement in Medical
Outcomes Study Sleep Problems Index II (MOS-II) scores compared with those assigned to either a
light-emitting or sound-producing sham pad (mean improvement from baseline for active versus sham
pad: 13.2 versus 6.2 points, p = 0.02) [18]. In descriptions of the two trials available on the company
website, however, the MOS-II was not a primary or secondary outcome measure and was tabulated
using 9 out of 12 questions from the MOS sleep scale, which itself was listed as a secondary
outcome.
Analysis of primary and secondary outcome measures revealed no differences in International
Restless Legs Syndrome Study Group (IRLS) scores (improvement from baseline for active versus
sham pad: 6.68 versus 6.39 points, p = 0.81) or RLS quality of life scores (improvement from
baseline: 11 versus 7 points, p = 0.14). Changes in the MOS sleep scale score were not reported. The
most common adverse effect of the vibratory pad was temporary worsening of RLS/WED symptoms,
reported in nine patients in the active group and two patients in the control group.
CHRONIC PERSISTENT SYMPTOMS Chronic persistent restless legs syndrome/WillisEkbom disease (RLS/WED) is defined as RLS/WED that is frequent and troublesome enough to
require daily treatment, with symptoms usually occurring at least twice a week on average and
resulting in moderate or severe distress [5].
Choice of therapy In patients who do not respond to nonpharmacologic therapy and correction of
iron deficiency, we recommend pharmacologic treatment with a dopamine agonist or an alpha-2-delta
calcium channel ligand as first-line therapy. These classes of drugs have been shown to be effective
compared with placebo in multiple randomized controlled trials [2-4,19-21].
Head-to-head comparisons between the two classes are limited to a single study [21], and we
therefore suggest choosing initial therapy based on consideration of symptom severity, patient age
and comorbidities, drug side effect profiles, and patient preferences (table 2) [5].
For patients with very severe RLS/WED, comorbid depression, or obesity/metabolic syndrome,
a dopamine agonist is preferred over other drugs as initial therapy.
For patients with comorbid pain, anxiety, or insomnia or a history of impulse control disorder or
addiction associated with use of a dopamine agonist, we suggest starting with an alpha-2-delta
calcium channel ligand.
For most other patients, we initially try an alpha-2-delta calcium channel ligand because of the
risk of augmentation with dopamine agonists, but other potential side effects of the various drugs
should also be considered. In general, older patients are more prone to side effects of alpha-2delta ligands. If the first drug chosen is ineffective or poorly tolerated, then a drug of the other
class should be tried.
Small randomized trials and observational studies also support the use of other agents, including
levodopa, benzodiazepines, and opioids, but generally these are reserved for intermittent use or in
patients with more refractory symptoms. (See 'Intermittent symptoms' below and 'Refractory
RLS' below.)
Drug dosages should be used at the minimum dose required to control symptoms. For dopaminergic
agents, the doses required for RLS/WED are lower than those used to treat Parkinson disease and
usually are given only in the evening (table 2). Ropinirole and rotigotine should be avoided in patients
with hepatic failure, as they are metabolized by the liver.
Patients on continuous therapy should be examined regularly (eg, every 6 to 12 months) and
screened for side effects and complications such as augmentation, which is a common complication
of long-term dopaminergic therapy [17]. (See 'Augmentation' below.)
Dopamine agonists Dopamine agonists belong to a class of drugs that directly stimulate
dopamine receptors and have a longer half-life (four to six hours) than levodopa (90 minutes). They
are generally superior to levodopa for the treatment of daily RLS/WED, because of the lower risk of
complications.
In a 2011 meta-analysis of 38 trials evaluating dopamine agonists for the treatment of RLS/WED that
included cabergoline, lisuride, pergolide, pramipexole, ropinirole,rotigotine, and sumanirole, all except
sumanirole were superior to placebo [2]. In two trials, cabergoline and pramipexole were superior to
levodopa for improvement in disease severity as measured by the International Restless Legs
Syndrome Study Group (IRLS) rating scale [22,23].
Pramipexole and ropinirole The non-ergot dopamine agonists, pramipexole and ropinirole, are
effective in the treatment of RLS/WED and are less likely to cause side effects than other dopamine
agonists (eg, cabergoline and pergolide) and levodopa. These agents, along with rotigotine, are
considered to be the dopamine agonists of choice for RLS/WED, and all three have been approved by
the US Food and Drug Administration (FDA) for this indication [3,5].
The benefit of pramipexole was demonstrated in a meta-analysis of seven randomized
placebo-controlled trials totalling over 1200 patients [3]. In all of the studies, pramipexole
improved RLS/WED symptom severity, with an average improvement in the IRLS rating scale of
6.7 points over placebo (95% CI 4.9-8.5) [3]. For reference, a 6-point difference has been
proposed as a clinically meaningful improvement in IRLS scores [24]. Uncontrolled studies with
longer-term follow-up (26 to 52 weeks) have reported a mean improvement of 17 points on the
IRLS scale [25,26].
The benefit of ropinirole was demonstrated in a meta-analysis of five randomized placebocontrolled trials totalling over 900 patients, in which the average improvement in IRLS score over
placebo was 4 points (95% CI 2-6) [3].
The onset of action for pramipexole and ropinirole is typically 90 to 120 minutes after intake.
Therefore, these medications should be started two hours beforeRLS/WED symptoms start [5]. The
recommended doses are as follows (table 2) [5]:
Pramipexole 0.125 mg once daily. The dose may be increased by 0.125 mg every two to three
days until relief is obtained. In a clinical trial, all three doses of pramipexole (0.25, 0.50, and 0.75
mg daily) were equally effective, and some patients responded to the initial dose of 0.125 mg
daily [27]. However, side effects were more common with the 0.50 mg and 0.75 mg daily doses.
Therefore, it is expected that 0.25 mg daily has the best therapeutic margin. Most patients
require 0.5 mg or less, but doses up to 1 mg may be needed.
Ropinirole 0.25 mg once daily. The dose may be increased by 0.25 mg every two to three days
until relief is obtained. Most patients require at least 2 mg, and doses up to 4 mg may be
needed. The maximum recommended dose is 3 mg in patients with end-stage renal disease on
hemodialysis. In one large randomized controlled trial, the average daily dose of ropinirole was
1.9 mg [28].
Adverse effects with pramipexole and ropinirole are usually mild, transient, and limited to nausea,
lightheadedness, and fatigue; these usually resolve within 10 to 14 days. Less frequent side effects
include nasal stuffiness, constipation, insomnia, and leg edema; these are reversible if the medication
is stopped. Excessive daytime sleepiness can occur at higher doses and occasionally manifests as
sudden, unexpected sleep attacks [29]. These may be less common than in patients with Parkinson
disease on higher doses of pramipexole [30].
As first reported in patients with Parkinson disease, dopamine agonist therapy in patients
with RLS/WED may be associated with an increased risk of impulse control disorders such as
pathologic gambling, compulsive eating and shopping, and compulsive inappropriate hypersexuality
[31,32]. (See "Pharmacologic treatment of Parkinson disease", section on 'Impulse control disorders'.)
Augmentation, which refers to a worsening of RLS/WED symptoms with increasing doses of
medication, including earlier onset of symptoms, increased intensity of symptoms, shorter duration of
drug action, or topographic spread of symptoms to the arms, is a common complication of long-term
dopaminergic therapy in RLS/WEDthat is discussed in more detail below. (See 'Augmentation' below.)
Early morning rebound symptoms have also been observed in some patients and should be
approached in a manner similar to augmentation. Doses of ropinirole andpramipexole should not
generally exceed the limits given above to avoid or reduce the risk of augmentation.
Dopamine withdrawal syndrome can occur with abrupt discontinuation of dopamine agonist therapy.
Symptoms include anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and
drug craving. (See "Pharmacologic treatment of Parkinson disease", section on 'Dopamine agonist
withdrawal syndrome'.)
Rotigotine Rotigotine is a non-ergot dopamine agonist that is formulated as a 24-hour transdermal
patch. Rotigotine was withdrawn from the United States and European markets in 2008 due to
problems with the delivery mechanism, but it was reintroduced in 2012.
The benefit of rotigotine for RLS/WED was demonstrated in a meta-analysis of five randomized
controlled trials totalling over 600 patients, in which the average improvement in IRLS score over
placebo was 7 points (95% CI 5.6-8.4) [3]. Two long-term follow-up studies (52 to 104 weeks) have
reported a mean improvement of 15 to 17 points on the IRLS scale [33,34].
Transdermal rotigotine is a once-daily patch that is typically started at 1 mg/24 hours and titrated
upwards to a maximum dose of 3 mg/24 hours. Application site reaction is the most common adverse
effect of rotigotine, reported by 40 to 50 percent of patients. To decrease the risk of skin reactions, the
manufacturer recommends rotating application sites, avoidance of direct sun exposure, and removal
of the patch during magnetic resonance imaging. Other side effects are similar to those seen with oral
dopamine agonists, including augmentation. (See 'Augmentation' below.)
Alpha-2-delta calcium channel ligands Gabapentin enacarbil, gabapentin, and pregabalin are
alternative choices for patients with chronic persistent RLS, and the FDA has approved gabapentin
enacarbil for this indication [5,35,36].
The alpha-2-delta calcium channel ligands may be particularly useful when RLS/WED occurs in the
setting of a painful peripheral neuropathy or an unrelated chronic pain syndrome and in patients with
comorbid insomnia or sleep disturbance that is disproportionate to other RLS/WED symptoms [20].
They are preferred over dopamine agonists in patients with impulse control disorders and are
probably more helpful than dopamine agonists in patients with comorbid anxiety.
They may also be considered in the treatment of RLS/WED in association with Parkinson disease,
since these patients may already be receiving dopaminergic therapy, or as an add-on therapy in
patients with a partial response to dopamine agonist therapy but intolerance to higher doses. Unlike
the dopamine agonists, they are not associated with augmentation.
As with other antiepileptic drugs (AEDs), the alpha-2-delta calcium channel ligands may be
associated with an increased risk of suicidal thoughts and behavior, and patients should be monitored
for emergent suicidality and depression. (See "Overview of the management of epilepsy in adults",
section on 'Specific adverse reactions'.)
Gabapentin enacarbil Several randomized, placebo-controlled studies have demonstrated
that gabapentin enacarbil is effective in reducing RLS/WEDsymptom severity [3]. In the largest study
of 325 patients, gabapentin enacarbil at a dose of 600 or 1200 mg/day was associated with a 3- to 4point improvement in IRLS scores compared with placebo [37]. In another randomized study,
gabapentin enacarbil also showed efficacy in decreasing the polysomnographic parameters of wake
time during sleep and number of periodic limb movements with arousals per hour of sleep [38].
The recommended dose of gabapentin enacarbil for RLS/WED is 600 mg, taken in the early evening
(eg, at 5 pm). Common adverse effects associated with gabapentin enacarbil include somnolence and
dizziness; these are generally mild to moderate and remit with time. In a 52-week open-label study,
two-thirds of patients reported mild to moderate side effects, leading to treatment discontinuation in 10
percent [39]. Somnolence, dizziness and weight gain were among the most common reasons for
discontinuation. Although not formally assessed with rating scales, augmentation was not recognized
in any patients based on retrospective review of adverse events.
Gabapentin More limited data also suggest that gabapentin may be effective in RLS/WED.
Gabapentin, mean dose 733 mg/day, was effective in a four-week open-label study of nine patients
with idiopathic RLS [40], and at a much higher mean dose (1855 mg) in a randomized, placebocontrolled trial of 22 patients [41]. Although this trial suggested that mean gabapentin doses of 1800
mg a day are needed, many patients appear to benefit from a lower dose.
We suggest beginning treatment at 100 to 300 mg per dose because of the tendency of the drug to
cause somnolence and gait unsteadiness [5]. Among dialysis patients, low-dose gabapentin (200 to
300 mg three times weekly after hemodialysis) was effective in a 12-week, double-blind crossover
study [42].
Pregabalin In a small randomized trial of 58 patients, pregabalin (starting dose 150 mg daily, mean
dose 337 mg daily) was superior to placebo for improving symptoms of RLS/WED [43].
In a subsequent larger randomized trial, pregabalin was compared with pramipexole and placebo in
719 patients with RLS/WED [21]. After 12 weeks of therapy, both pregabalin (300 mg daily) and
pramipexole (0.5 mg daily) were associated with a significant 3- to 4-point improvement in IRLS
scores compared with placebo. Over 40 to 52 weeks of treatment, pregabalin was noninferior to
pramipexole on measures of efficacy and was associated with a significantly lower augmentation rate
(2.1 percent) compared with pramipexole at a dose of 0.25 mg (5.3 percent) or 0.5 mg (7.7 percent).
In contrast, pregabalin was associated with a slightly higher rate of treatment discontinuation due to
side effects (28 percent, versus 19 and 24 percent for pramipexole 0.25 mg and 0.5 mg daily,
respectively). Suicidal ideation was reported in six patients taking pregabalin and in five patients
taking pramipexole.
Similar to gabapentin enacarbil, pregabalin may also improve subjective and objective measures of
sleep maintenance and total sleep time in patients with RLS and comorbid insomnia [44].
We suggest starting pregabalin at a dose of 50 to 75 mg per day. The usual effective dose is 150 to
450 mg. The most common side effects reported with pregabalin include dizziness, somnolence,
fatigue, headache, peripheral edema, and weight gain [21,43].
Duration of therapy RLS/WED is often a lifelong disease, but the optimal and safe duration of
pharmacologic therapy has not been well established [20]. Most of the supporting data are based on
relatively short (12-week) randomized trials, with fewer long-term extension studies supporting
efficacy for 6 to 12 months of therapy with either a dopamine agonist or gabapentin enacarbil.
In clinical practice, the most common problems that arise with long-term therapy are loss of efficacy
and augmentation. (See 'Augmentation' below and 'Refractory RLS' below.)
INTERMITTENT SYMPTOMS
Choice of therapy In patients with mild or intermittent symptoms, nonpharmacologic therapies
may be sufficient for symptom relief. In other patients, clinically significant symptoms do not occur
frequently enough to require daily treatment but are nonetheless disabling when they do occur. For
such patients, we suggest use of levodopa or a dopamine agonist on an as-needed basis. While this
approach has not been systematically studied in clinical trials, clinical experience suggests that it is a
reasonable strategy.
The use of dopamine agonists in restless legs syndrome/Willis-Ekbom disease (RLS/WED) is
discussed in more detail above (see 'Dopamine agonists' above). Other treatment options include
intermittent use of levodopa, a benzodiazepine, or a low-potency opioid [5]. (See 'Levodopa' below
and 'Benzodiazepines' below and'Opioids' below.)
Levodopa Levodopa was the first drug to be formally studied in RLS/WED, and its ability to
ameliorate symptoms of RLS/WED has long been recognized. However, use of levodopa
for RLS/WED has waned over time as the risk for augmentation has been better characterized, and
as other dopaminergic agents that have a lower risk for augmentation have become available.
(See 'Augmentation' below.)
Levodopa remains a reasonable "on demand" treatment option for patients with intermittent RLS who
do not require daily therapy [3,5].
Several small randomized studies have demonstrated that levodopa improves RLS/WED symptom
severity, number of periodic limb movements in sleep (PLMS), self-rated sleep quality, and quality of
life compared with placebo [45]. Most studies were performed before the International Restless Leg
Syndrome Study Group (IRLS) rating scale became widely used as an outcome measure; in two
studies that reported RLS/WED symptom severity on a 10-point scale, levodopa improved symptom
severity by a mean of 1.34 points compared with placebo [45]. Levodopa was also effective in a
double-blind study of uremic RLS/WED [46].
Short-term therapy with levodopa is generally well tolerated; common adverse effects such as
nausea, dizziness, and somnolence are usually mild and improve over time. Other problems that may
occur in patients on levodopa include symptom rebound in the early morning (20 to 35 percent) or in
the second half of the night [47,48]. Controlled release (CR) carbidopa-levodopa combined with
standard carbidopa-levodopa may help sleep quality during the second half of the night for patients
who experience recurrence [49].
For best absorption, levodopa should not be taken with high protein foods. Suggested agents include:
Carbidopa-levodopa 25 mg/100 mg, one-half or one tablet, can be used as a starting dose for
intermittent RLS/WED that occurs during the evening, at bedtime, or on waking during the night.
Additionally, this medication may be helpful for RLS/WED associated with specific triggers
including lengthy travel by auto or airline, or spectator events with prolonged sitting. Levodopa
doses greater than 200 mg per day should be avoided.
Carbidopa-levodopa CR, starting at 25 mg/100 mg before bed, may be helpful
for RLS/WED symptoms that awaken the patient during the night.
Benzodiazepines Benzodiazepines can be useful in mild cases of RLS/WED, particularly in
younger patients [50,51]. The best-studied benzodiazepine inRLS/WED is clonazepam.
In a small randomized, double-blind, crossover trial, treatment with clonazepam, 1 mg daily, was
superior to placebo in six patients with RLS/WED [52]. In an open trial, 14 of 15 patients
with RLS/WED due to uremia responded to clonazepam, 1 to 2 mg daily [53]. Clinical experience
suggests that clonazepam is useful in some patients at 0.5 mg daily.
Although most trials have been performed with clonazepam, its long duration of action may result in
more adverse effects, such as nocturnal unsteadiness, drowsiness or cognitive impairment in the
morning, impotence, and exacerbation of sleep apnea [54]. However, at least one study has shown a
low rate of adverse effects from clonazepam in older adult patients [50].
Long-term maintenance treatment with benzodiazepines is limited by tolerance in many patients, but
abuse appears to be low in this disorder. Because of tolerance and the potential for side effects, use
of benzodiazepines for RLS/WED is generally limited to those patients that require only intermittent
therapy, or as an add-on agent in patients with refractory symptoms.
Short-acting benzodiazepine receptor agonists such as zolpidem should generally be avoided, as a
high frequency of sleepwalking and sleep-related eating disorder has been reported with their use in
the setting of RLS/WED (as high as 80 percent in one study of 15 patients) [55-57].
AUGMENTATION Augmentation is the main complication of long-term dopaminergic therapy for
restless legs syndrome/Willis-Ekbom disease (RLS/WED). It refers to an overall increase
in RLS/WED symptom severity with increasing doses of medication, including earlier onset of
symptoms, increased intensity of symptoms, shorter duration of drug action, or topographic spread of
symptoms to other body parts, including the trunk and arms.
Augmentation should be considered a possibility in the following circumstances [58]:
A maintained increase in symptom severity despite appropriate treatment
A maintained increase in symptom severity following a dose increase, particularly if a dose

reduction leads to an improvement in symptoms
Earlier onset of symptoms in the afternoon/evening
Topographic spreading of symptoms to previously unaffected body parts
Shorter latency to symptom onset during the day when at rest
Shorter duration of action of the drug
Augmentation was first recognized in patients taking levodopa. In one study of 23 patients with
severe RLS/WED treated with a combination of regular release and sustained-release levodopa
(mean total daily dose of levodopa, 388 mg), two-thirds of patients stopped therapy before the end of
the planned year of therapy due to increased severity of RLS during the day [59]. In a multicenter
open-label study using flexible dosing of levodopa (mean maximum daily dose, 311 mg), 60 percent of
patients developed augmentation at a median time of 71 days into therapy, leading to treatment
discontinuation in 12 percent [60]. Augmentation was significantly more common in patients taking
greater than or equal to 300 mg of levodopa daily (70 versus 35 percent).
The risk of augmentation with dopamine agonists appears to be lower but not insignificant; it has been
reported in 3 to 9 percent of patients taking pramipexole for one year [21], about one-third of patients
taking pramipexole for two years [61], and 42 to 68 percent of patients taking pramipexole for 8 to 10
years [29,62]. Fewer studies have been performed on ropinirole, but it appears that the short-term
augmentation rate is similar to that of pramipexole. Augmentation has been reported in 2 to 9 percent
of patients taking rotigotine for one year [34,63,64] and 38 percent of those using rotigotine for five
years (only clinically significant in 13 percent) [65]. The definition of augmentation and the method of
assessment (ie, retrospective or prospective) have varied across studies, and therefore direct
comparisons are difficult.
The risk of augmentation increases with higher daily doses, longer duration of use, and lower iron
stores [21,66]. Other risk factors for augmentation are not well known; in one study, augmentation was
significantly more common in patients with a family history of RLS/WED and in those who had no
evidence of neuropathy on electromyography or nerve conduction studies [67].
Using dopaminergic drugs on an intermittent basis rather than continuously may lower the risk of
augmentation, although this has not been well studied. This is the rationale for use of levodopa in
patients with intermittent RLS/WED, despite the high risk of augmentation with continuous use.
Alpha-2-delta calcium channel ligands have not been associated with augmentation.
Management of augmentation has not been systematically studied, but several strategies can be used
when it is recognized in patients on dopamine agonists.
For mild augmentation, the dose of a dopamine agonist can be split between a nighttime dose
and a dose earlier in the day. If this is ineffective, the dose can be modestly increased, but
caution should be used not to exceed the maximum recommended total daily dosage. In
addition, the patient should be carefully followed to ensure that augmentation is not worsening.
For more severe augmentation, switching from pramipexole or ropinirole to the extended
release preparation, rotigotine, can sometimes help, as the rate of significant augmentation may
be less with rotigotine.
Alternatively, dopamine agonists can be discontinued and replaced with alpha-2-delta calcium
channel ligands [5]. We typically introduce the new drug and increase the dose to an effective
level before slowly reducing the dopamine agonist and discontinuing if at all possible. Some
experts advocate a 10-day wash-out period before introducing the alpha-2-delta ligand in order
to establish a baseline measure of disease severity, but this can result in
increased RLS/WEDsymptoms and profound insomnia during the wash-out period.
Iron stores should be re-evaluated and iron replacement initiated if stores are low. (See 'Iron
replacement' above.)
REFRACTORY RLS Refractory restless legs syndrome/Willis-Ekbom disease (RLS/WED) is
defined as restless legs unresponsive to monotherapy with tolerable doses of a dopamine agonist or
alpha-2-delta ligand due to reduced efficacy, augmentation, or adverse effects [5].
In patients with refractory symptoms, iron stores should be re-evaluated and iron replacement initiated
if stores are low. Lifestyle practices, concomitant medications, and treatment adherence should also
be reviewed. (See 'Iron replacement' above and 'Avoidance of aggravating factors' above.)
Referral to a specialist for RLS/WED management should be considered for these patients [54]. The
main pharmacologic treatment options are:
Use a combination of agents, such as a dopamine agonist, alpha-2 delta ligand, and/or a
benzodiazepine. (See 'Dopamine agonists' above and 'Alpha-2-delta calcium channel
ligands' above and 'Benzodiazepines' above.)
Change to a high-potency opioid. (See 'Opioids' below.)
Opioids Opioids can be effective in the treatment of chronic and refractory RLS/WED, particularly
for patients who have not responded to other therapies. A variety of opioids,
including oxycodone, codeine, propoxyphene, methadone, and tramadol, have been reported to be
helpful for RLS/WED, primarily in uncontrolled trials [3,59].
In a double-blind, four-week crossover study of 11 patients, oxycodone (mean dose 16 mg/day) was
superior to placebo with regard to number of sleep arousals, periodic leg movement frequency, and
sleep efficiency [68]. One long-term retrospective study of 113 patients treated with opioids
demonstrated persistent benefit, but a small number of patients developed sleep apnea [69].
In a double-blind, multicenter trial of 276 patients with refractory RLS/WED, controlled
release oxycodone-naloxone was significantly more effective than placebo at 12 weeks (mean
difference in International Restless Legs Syndrome Study Group [IRLS] scores: 8.15) [70]. The mean
daily dose of oxycodone was 22 mg. Benefit was preserved over a 40-week, open-label extension
period. Fatigue and constipation were the most common side effects; two patients developed ileus or
sub-ileus. No augmentation was seen.
In a 10-year, open-label study of methadone for RLS/WED, 15 percent of 76 patients discontinued

methadone treatment in the first year, but the remainder continued to use it with benefit. The mean
daily dose after six months was 10 mg, with subsequent increases of no more than 10 mg [62].
Low potency opioids or opioid agonists can be used for intermittent RLS [54]. These drugs are usually
taken before bed and include:
Codeine 30 to 60 mg.
Tramadol 50 to 100 mg before bed or during the night. Of note, tramadol has also been
reported to cause augmentation in some patients [15].
Similar to benzodiazepines, tolerance to high potency opioids can develop with long-term
maintenance therapy, but opioid abuse potential appears to be low in patients with RLS/WED in the
absence of a history of substance abuse. Nevertheless, we typically restrict use to patients with more
severe symptoms who fail to respond to other agents. Potential side effects include constipation,
nausea, fatigue, itchiness, unsteadiness, and exacerbation of sleep apnea. Agents include [54]:
Oxycodone 5 to 30 mg
Hydrocodone 5 to 30 mg
Methadone 2.5 to 20 mg
Other drugs Other drugs that may be useful in RLS/WED but have been reported in only a small
number of (mainly open-label) studies include carbamazepine(mean dose
236 mg/day) [71], clonidine (0.05 mg/day) [72], and amantadine (up to 300 mg/day) [73]. There is
inadequate evidence to suggest that magnesium supplementation is an effective treatment
for RLS/WED.
SPECIAL POPULATIONS
Pregnancy and lactation Management of restless legs syndrome/WillisEkbom disease (RLS/WED) during pregnancy should be individualized based on symptom severity,
comorbidities such as depression or anxiety, and patient preferences.
Many patients can be managed successfully with education, reassurance, iron supplementation if
indicated, and nonpharmacologic strategies. Pharmacologic therapies such
as clonazepam or carbidopa-levodopa may be considered for severe symptoms in women who wish
to try medication. (See "Restless legs syndrome/Willis-Ekbom disease during pregnancy and
lactation".)
End-stage renal disease The management of RLS/WED in patients with end-stage renal disease
is similar to that in patients with normal renal function. However, medication doses may need to be
adjusted, especially if the patient is not yet receiving dialysis, as dopamine agonists and alpha-2-delta
ligands are all excreted by the kidneys. Careful attention to iron status is especially important in this
group [74]. (See "Sleep disorders in end-stage renal disease", section on 'Treatment'.)
PERIODIC LIMB MOVEMENT DISORDER Periodic limb movements of sleep (PLMS) accompany
many sleep and neurologic disorders, including restless legssyndrome/WillisEkbom disease (RLS/WED), obstructive sleep apnea, rapid eye movement (REM) sleep behavior
disorder, narcolepsy, and Parkinson disease. PLMS increase in frequency with age. (See "Clinical
features and diagnosis of restless legs syndrome/Willis-Ekbom disease and periodic limb movement
disorder in adults", section on 'Periodic limb movements of sleep'.)
PLMS do not have a consistent relationship with symptoms (eg, insomnia, excessive daytime
sleepiness) or with polysomnographic variables of sleep disruption. They are generally considered to
be an age-related phenomenon, a response to arousals, or an epiphenomenon of other disorders.
However, occasionally they occur abundantly with frequent electroencephalographic arousals in the
absence of other disorders, leading the clinician to suspect that they are directly responsible for
complaints of excessive sleepiness or insomnia. The term periodic limb movement disorder (PLMD)
should be restricted to this subgroup.
For patients with PLMS associated with RLS/WED, treatment should concentrate on the symptoms
of RLS/WED rather than on the leg movements. For PLMS associated with other sleep disorders,
independent treatment of PLMS is rarely required.
There are limited data regarding management of PLMD. Polysomnographic studies of PLMS
in RLS/WED have shown reduction in the periodic limb movement index
with pramipexole, ropinirole, rotigotine, gabapentin, gabapentin enacarbil, and pregabalin [3,38,75]. A
comparison study suggested greater reduction with pramipexole compared with pregabalin [44].
Extrapolating from this data, we suggest a trial of dopamine agonist therapy in suspected cases of
PLMD. If there are contraindications to dopamine agonist therapy, an alpha-2-delta ligand can be
tried. Dosing and safety considerations are the same as for use in RLS/WED. (See 'Dopamine
agonists' above and 'Alpha-2-delta calcium channel ligands' above.)
If the primary symptoms of insomnia or sleepiness do not respond to adequate doses of the selected
drug, then the patient should be re-evaluated for other causes of insomnia or excessive daytime
sleepiness. (See "Clinical features and diagnosis of insomnia" and "Approach to the patient with
excessive daytime sleepiness".)
Clonazepam, valproate, and selegiline have been reported to help PLMD in small, uncontrolled
studies [3]. It would appear, however, that clonazepam reduces arousals rather than eliminates PLMS.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade reading level
and are best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
Basics topic (see "Patient information: Restless legs syndrome (Willis-Ekbom disease) (The
Basics)" and "Patient information: Nocturnal (nighttime) leg cramps (The Basics)")
Online information and support is available for patients with RLS/WED through The Restless Legs
Syndrome Foundation and the American Academy of Sleep Medicine (yoursleep.aasmnet.org).
SUMMARY AND RECOMMENDATIONS Restless legs syndrome/WillisEkbom disease (RLS/WED) is a treatable condition that generally responds well to pharmacologic
therapy. A variety of treatments for RLS/WED have been studied in randomized controlled trials. The
goals of therapy are to reduce or eliminate symptoms of RLS/WED and improve daytime function,
sleep, and quality of life.
Iron stores should be evaluated in all patients with suspected or established RLS/WED. We
suggest a trial of oral iron therapy for patients with iron deficiency or low-normal ferritin levels (ie,
serum ferritin level <75 mcg/mL) (Grade 2C). (See 'Iron replacement' above.)
Nonpharmacologic therapy options include avoidance of aggravating drugs and substances
such as caffeine (table 1), mental alerting activities, short daily hemodialysis for patients in renal
failure, exercise, leg massage, and applied heat. In patients with mild and/or intermittent
symptoms, these therapies may be sufficient for symptom relief. (See 'Nonpharmacologic
therapy' above.)
In patients with chronic persistent RLS/WED despite nonpharmacologic therapies, we
recommend pharmacologic therapy with a non-ergot dopamine agonist or an alpha-2-delta
calcium channel ligand (Grade 1B). The choice between the two classes of drugs is based on
symptom severity, patient age and comorbidities, drug side effect profiles, and patient
preferences. (See 'Choice of therapy' above.)
For patients with very severe RLS/WED, comorbid depression,
or obesity/metabolic syndrome, we suggest initial therapy with a dopamine agonist
(pramipexole, ropinirole, or rotigotine) rather than an alpha-2-delta calcium channel ligand
(Grade 2C). (See 'Dopamine agonists' above.)
For patients with comorbid pain, anxiety, or insomnia or a history of impulse control
disorder or addiction associated with use of a dopamine agonist, we suggest starting with
an alpha-2-delta calcium channel ligand (gabapentin enacarbil, gabapentin, or pregabalin)
(Grade 2C). (See 'Alpha-2-delta calcium channel ligands' above.)
For most other patients, we initially try an alpha-2-delta calcium channel ligand because of
the risk of augmentation with dopamine agonists, but other potential side effects of the
various drugs should also be considered. In general, older patients are more prone to side
effects of alpha-2-delta ligands. If the first drug chosen is ineffective or poorly tolerated,
then a drug of the other class should be tried.
In patients with intermittent symptoms that are not frequent enough to require daily therapy but
are nonetheless disabling when they do occur, we suggest a trial of a dopamine agonist or
levodopa on an as-needed basis (Grade 2C). Other treatment options for intermittent symptoms
include benzodiazepines and opioids. (See 'Intermittent symptoms' above.)
When RLS/WED symptoms are refractory to first-line therapy with a dopamine agonist or an
alpha-2-delta calcium channel ligand, treatment options include combination therapy and
opioids. (See 'Refractory RLS' above.)
Augmentation, which refers to an overall worsening of RLS/WED symptom severity, with earlier
onset of symptoms, shorter symptom latency with rest, shorter duration of action of drugs, or
spread of symptoms to trunk or arms, is the most common complication of long-term
dopaminergic therapy. Augmentation may be managed by alteration in the treatment regimen.
(See 'Augmentation' above.)
RLS/WED is common during pregnancy. Many patients can be managed successfully with
education, reassurance, iron supplementation if indicated, and nonpharmacologic strategies.
Pharmacologic therapies such as clonazepam and carbidopa-levodopa may be considered for
severe symptoms. (See "Restless legs syndrome/Willis-Ekbom disease during pregnancy and
lactation".)
Treatment of periodic limb movement disorder (PLMD) as an entity distinct from RLS/WED is
not well studied, but the approach is similar to that of RLS/WED. Periodic limb movements of
sleep (PLMS) in the absence of insomnia or excessive daytime sleepiness do not require
treatment. (See 'Periodic limb movement disorder' above.)
ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Robert Sheon,
MD, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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syndrome. Mov Disord 2000; 15:324.
74.
Giannaki CD, Hadjigeorgiou GM, Karatzaferi C, et al. Epidemiology, impact, and treatment
options of restless legs syndrome in end-stage renal disease patients: an evidence-based review.
Kidney Int 2014; 85:1275.
75.
Oertel WH, Benes H, Garcia-Borreguero D, et al. Rotigotine transdermal patch in moderate to

severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study.
Sleep Med 2010; 11:848.
Topic 88241 Version 19.0
http://www.uptodate.com/contents/treatment-of-restless-legs-syndrome-willisekbom-disease-and-periodic-limb-movement-disorder-in-adults
Untuk RLS ringan, gejala dapat membaik dengan terapi non-farmakologi, yaitu
dengan program latihan atau olahraga yang dilakukan rutin. Penggunaan mandi air
panas, pijat pada tungkai, dan heating pads dapat mengurangi gejala. Disamping
itu, penting juga untuk menghindari konsumsi alkohol karena dapat mengurangi
dan menurunkan kulaitas tidur sehingga dapat menyebabkan eksaserbasi RLS.
Pemberian preparat besi secara oral maupun intravena dapat mengurangi gejala
pada pasien RLS dengan kadar feritin serum rendah. Terapi pada RLS dapat
meliputi obat-oabt sebagai berikut :
1. Agonis Dopamin
Merupakan first-line teratment untuk RLS.
Memiliki
efek
terhadap
level
dopamin
otak
yang
merupakan
neurotransmitter yang berperan penting dalalm sistem saraf pusat.
Contoh : ropinirole (Requip), pramipexole (Mirapex), pergolide (Permax)
Agen dopaminergik lainnya seperti levodopa (Sinemet) dapat digunakan

untuk RLS, tetapi memiliki efektifitas rendah serta efek samping yang lebih
banyak dibandingkan agonis dopamin.
2. Benzodiazepin
Obat golongan ini memiliki efektivitas yang lebih rendah dalam
mengurangi gejala RLS, tetapi memiliki kelebihan dalam meningkatkan
kualitas tidur. Dosis kecil benzodiazepin dapat digunakan untuk menangkal
efek stimulasi dari agonis dopamin.
Contoh : clonazepam (Klonipin)
3. Anti-konvulsan
Dianggap berpotensi rendah dibanding agonis dopamin.
Pilihan efektif untuk RLS ringan atau untuk paien yang tidak toleransi
terhadap agonis dopamin. Juga sangat berguna untuk pasien dengan sensai
nyeri.
Contoh : gabapentin (Neurontin)
4. Opioid
Digunakan pada pasien dengan gejala berat yang tidak respon terhadap
terapi farmakologi lainnya. Terapi ini juga dapat digunakan sebgai antinyeri.
Contoh : kodein, propoxyphene (Darvon)

Introduction To RLS

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Introduction To RLS

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Introduction to RLS

What is restless legs?

What are the symptoms of restless legs?

What causes RLS?

People with low iron levels or anaemia may be prone to developing

Chronic diseases such as kidney failure, diabetes, Parkinson's

Some pregnant women experience RLS, especially in their last

Certain medications-such as antinausea drugs (prochlorperazine or

How is RLS diagnosed?

1. a desire to move the limbs, often associated with paresthesias or

How is RLS treated?

Restless legs syndrome and related

RLS and PLMD:

Periodic Limb Movement Disorder

While treatments for the two conditions are similar, PLMD is a

RLS may often have a genetic basis, particularly in those who

Other research suggests that restless

Some experts suggest that RLS, particularly if it occurs in

Abnormalities of Iron Metabolism

An international study showed that 2% of children ages 8 - 17

Attention Deficit Hyperactivity Disorder

Other Conditions Associated with Restless Legs

Varicose veins. Varicose veins occur in about 1 in 7 patients with RLS.

Fibromyalgia (chronic pain of unknown cause)

Emphysema (a lung disease usually caused by smoking)

Sleep apnea (pauses in breathing during sleep) and snoring

Brain or spinal injuries

Click the icon to see an image of hypothyroidism.

Click the icon to see an image detailing fibromyalgia.

Click the icon to see an image detailing rheumatoid arthritis.

Click the icon to see an image detailing emphysema.

Environmental and Dietary Factors

Caffeine (coffee drinking is specifically associated with PLMD)

Prolonged exposure to cold

Calcium channel blockers (mostly used to treat high blood pressure)

Metoclopramide (used to treat various digestive diseases)

Risk Factors for Periodic Limb Movement

sleeping patterns can have significant effects on a person's

How would you describe your sleep problem?

How many times a week does the problem occur?

How restful is your sleep?

What is your sleep environment like? Noisy? Not dark enough?

Are you a shift worker?

Keeping a Record of Sleep.

To help answer these questions, the patient

Sleep Disorders Centers

Insomnia due to psychological disorders

Sleeping problems due to substance abuse

Severe restless legs syndrome

Persistent daytime sleepiness

Sudden episodes of falling asleep during the day (possible narcolepsy)

To undergo the test, the patient arrives about 2 hours before

Changes in breathing and blood levels of oxygen

The Epworth Sleepiness Scale

1= slight chance of dozing

1= slight chance of dozing

Sitting inactive in a public place

1= slight chance of dozing

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

1= slight chance of dozing

1= slight chance of dozing

Sitting and talking to someone

1= slight chance of dozing