Restless legs syndrome

Restless leg syndrome also called Willis-Ekbom disease, is a common neurologic and sleep related movement disorder that is characterized by an irresistible urge to move the legs while at rest, usually because of uncomfortable sensations that are often likened to crawling, cramping, aching, burning, itching, or prickling deep within the affected areas, with relief upon leg movement or getting up to walk ¹. Restless legs syndrome typically happens in the evening or nighttime hours when you’re sitting or lying down. Restless legs syndrome causes unpleasant or uncomfortable sensations in the legs and an irresistible urge to move them ². People typically describe restless legs syndrome symptoms as compelling, unpleasant sensations in their legs or feet. They usually happen on both sides of the body. Less commonly, the sensations affect the arms. There is an association with involuntary jerking movements of the legs during sleep, known as periodic leg movements of sleep ³.

In the United States, there are more than three million cases of restless legs syndrome per year. Restless legs syndrome can begin at any age, even during childhood and generally worsens as you age. Restless leg syndrome is more common with increasing age and appears to be about twice as common in women than men. Men may be more likely to have periodic leg movements during sleep and experience less deep sleep as a result. In contrast, women appear to suffer more from sensory symptoms, leading to less satisfying sleep overall ⁴. Associated symptoms may become apparent at any age, and restless legs syndrome is usually chronic, often becoming more severe with increasing age. However, in some affected individuals, restless legs syndrome symptoms may periodically subside and recur with varying levels of severity. According to some reports, although most individuals do not bring their symptoms to the attention of physicians until middle age, up to 40 percent may initially experience symptoms before age 20.

The main symptom of restless leg syndrome is an urge to move your legs. Common accompanying characteristics of restless legs syndrome include:

• Sensations that begin while resting. The sensation typically begins after you’ve been lying down or sitting for an extended time, such as in a car, airplane or movie theater.
• Relief with movement. The sensation of restless legs syndrome lessens with movement, such as stretching, jiggling the legs, pacing or walking.
• Worsening of symptoms in the evening. Symptoms occur mainly at night.
• Nighttime leg twitching. Restless legs syndrome may be associated with another, more common condition called periodic limb movement of sleep, which causes the legs to twitch and kick, possibly throughout the night, while you sleep.

The words and phrases most commonly used by restless legs syndrome patients to describe the feelings are:

• “Twitchy”
• “Uncomfortable”
• “Restless”
• “Need to stretch”
• “Urge to move”
• “Legs want to move on their own”

The sensations also known as paresthesias or dysesthesias, which generally occur within the limb rather than on the skin. Restless legs syndrome patients use the following terms to describe the sensations that they commonly feel inside the shin, or between the knee and ankle:

• Crawling like having insects crawling inside the legs
• Creeping
• Tingling
• Pulling
• Tugging
• Throbbing
• Aching
• Burning
• Itching
• Electric

Sometimes the sensations are difficult to explain. People with restless legs syndrome usually don’t describe the condition as a muscle cramp or numbness. They do, however, consistently describe the desire to move the legs.

For some people, these sensations are merely uncomfortable. For others, they may actually cause pain. It’s common for symptoms to fluctuate in severity. Sometimes, symptoms disappear for periods of time, then come back. Symptoms range from mild to severe and may occur occasionally, a few times a week, or every night. They may disappear for weeks or months at a time and then come back. The sensations are usually felt on both sides of the body, though some people may find they alternate back and forth or stay limited to one side. The severity of restless legs syndrome symptoms generally increases with age.

People with restless legs syndrome often resort to a variety of movements to get relief, such as stretching, rubbing or kicking the legs, as well as getting up and walking around. This constant movement makes it difficult to settle down for sleep. For some people, deep sleep is only possible in the early morning, when symptoms tend to be less severe. However, their symptoms present, individuals with restless legs syndrome frequently report sleep problems and corresponding fatigue the next day.

Restless legs syndrome symptoms often make it difficult for you to fall asleep or rest and lead to functional impairments in mood, cognition, energy, and other daily activities ¹. The severity of impairment from restless legs syndrome is commonly measured subjectively by rating scales such as the International Restless Legs Syndrome Study Group rating scale (IRLS) or its self-administered version, the sIRLS ⁵. Both scales use ten questions to examine the severity of restless legs syndrome symptoms in relation to the patient’s mood, normal everyday functioning, frequency, sleep quality, and overall discomfort ⁶.

Restless legs syndrome may be primary (idiopathic or unknown cause) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency. Genetic predisposition with a family history is common ⁷. The pathogenesis of restless legs syndrome remains unclear but is likely to involve central nervous system dopaminergic dysfunction, as well as other, undefined contributing mechanisms.

Here is what scientists know about restless legs syndrome:

• Restless legs syndrome often runs in families. This is called primary or familial restless legs syndrome. Between 40% and 90% of patients with restless legs syndrome have at least one first-degree relative (parent, sibling, or child) with the condition. Researchers have identified some genetic changes that increase risk for restless legs syndrome, but it is likely that more have yet to be discovered.
• Restless legs syndrome sometimes appears to be a result of another condition, such as iron deficiency, anemia, kidney failure, or peripheral neuropathy, which, when present, worsens the underlying restless legs syndrome. This is called secondary restless legs syndrome.
• Up to 25 percent of women develop restless legs syndrome during pregnancy (during the third trimester), but symptoms often disappear after giving birth ⁸, ⁹. However, some women may continue to have symptoms after giving birth or may develop restless legs syndrome again later in life.
• Anemia and low iron levels (ferritin) frequently contribute to a worsening of restless legs syndrome symptoms.
• Restless legs syndrome is very common in patients requiring dialysis for end-stage renal disease.
• Some medications may appear to cause or aggravate restless legs syndrome symptoms, such as certain antipsychotic, antidepressant or antinausea drugs.
• Damage to the nerves of the hands or feet (i.e., peripheral neuropathy) from any number of causes, including diabetes, contributes to restless legs syndrome.
• Attention deficit hyperactivity disorder (ADHD) is common in children and adults with restless legs syndrome.

Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms, especially when augmentation develops. Augmentation syndrome is defined as a worsening of restless legs syndrome symptoms that occurs after starting a dopaminergic medication to treat restless legs syndrome. The medication is effective when it’s first started, but over time symptoms worsen or return to what symptoms were like prior to starting the treatment. Augmentation syndrome is characterized by more intense symptom severity, earlier symptom occurrence, and often, symptom spread from the legs to the arms or other body regions.

Restless legs syndrome can be treated, with care directed toward relieving symptoms. Certain lifestyle changes and activities may provide some relief in persons with mild to moderate symptoms of restless legs syndrome. Some people with restless legs syndrome have adequate symptom control with non-pharmacological measures such as massaging the legs, taking a warm bath, using a heating pad or ice pack, avoiding or decreasing the use of alcohol and tobacco, changing or maintaining a regular sleep pattern and moderate exercise. Moving the affected limb(s) may provide temporary relief.

There are new medical devices that have been cleared by the U.S. Food & Drug Administration (FDA), including a foot wrap that puts pressure underneath the foot and another that is a pad that delivers vibration to the back of the legs. Aerobic and leg-stretching exercises of moderate intensity also may provide some relief from mild symptoms.

Sometimes restless legs syndrome symptoms can be controlled by finding and treating an associated medical condition, such as peripheral neuropathy, diabetes, or iron deficiency anemia.

First-line pharmacological management options include iron-replacement therapy in those with evidence for reduced body-iron stores (low or low-normal blood tests called ferritin and transferrin saturation) or, alternatively, with prescribed gabapentin or pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine. Iron supplements are available over-the-counter. A common side effect of iron-replacement therapy is upset stomach, which may improve with use of a different type of iron supplement. Because iron is not well-absorbed into the body by the gut, it may cause constipation that can be treated with a stool softeners such as polyethylene glycol. In some people, iron supplementation does not improve a person’s iron levels. Others may require iron given through an IV line in order to boost the iron levels and relieve symptoms.

Second-line therapies include intravenous iron infusion in those who are intolerant of oral iron and/or those having augmentation with intense, severe restless legs syndrome symptoms, and opioids including tramadol, oxycodone, and methadone are typically reserved for patients who have failed other pharmacologic agents ¹⁰.

Restless legs syndrome types

There are two types of restless legs syndrome:

1. Primary restless legs syndrome is the most common type of restless legs syndrome. It is also called idiopathic restless legs syndrome. “Primary” means the cause is not known. Primary restless legs syndrome, once it starts, usually becomes a lifelong condition. Over time, symptoms tend to get worse and occur more often, especially if they began in childhood or early in adult life. In milder cases, there may be long periods of time with no symptoms, or symptoms may last only for a limited time. It is known, that primary restless legs syndrome tends to run in families. People whose parents have restless legs syndrome are more likely to develop the disorder. This suggests that there may be a genetic link that increases the chance of getting restless legs syndrome.
2. Secondary restless legs syndrome is restless legs syndrome that is caused by another disease or condition or, sometimes, from taking certain medicines. Symptoms usually go away when the disease or condition improves, or if the medicine is stopped.
   1. Some of the diseases and conditions that can cause restless legs syndrome are:
      • Iron deficiency (with or without anemia)
      • Kidney failure
      • Diabetes
      • Parkinson’s disease
      • Damage to the nerves in the hands or feet (peripheral neuropathy)
      • Neurologic lesions (spinal cord tumors, peripheral nerve lesions, or spinal cord injury)
      • Rheumatoid arthritis
      • Pregnancy. Restless legs syndrome is common in pregnant women. It usually occurs during the last 3 months of pregnancy and usually improves or disappears within a few weeks after delivery. However, some women may continue to have symptoms after giving birth or may develop restless legs syndrome again later in life.
      • Thyroid problems
      • Sleep apnea or narcolepsy
      • Varicose veins or trouble with the nerves in the hands or feet
      • Alcoholism
   2. Some of the types of medicines that can cause restless legs syndrome are:
      • Antiseizure medicines
      • Anti-nausea medicines (such as Antivert, Compazine, and Dramamine)
      • Antidepressants (such as Prozac, Effexor, and Lexapro)
      • Antipsychotics (used for bipolar disorder and schizophrenia)
      • Some cold and allergy medications containing antihistamines (such as Benadryl, NyQuil, and Dimetapp).
      • Restless legs syndrome symptoms usually go away when the medicine is stopped.
   3. Certain substances can trigger restless legs syndrome symptoms or make them worse. These substances include:
      • Caffeine
      • Alcohol
      • Tobacco

Restless Legs Syndrome and Periodic Limb Movement Disorder

Most people who have restless legs syndrome (RLS) also have a condition called periodic limb movement disorder (PLMD) ¹¹. Periodic limb movement disorder (PLMD) is a condition in which a person’s legs twitch or jerk uncontrollably about every 10 to 60 seconds. This usually happens during sleep. Periodic limb movement disorder (PLMD) involves repetitive flexing or twitching of the limbs while asleep at night. PLMD usually affects the legs but can also affect the arms. Periodic limb movement disorder (PLMD) is different from restless legs syndrome in that these movements are not accompanied by uncomfortable sensations and because they occur during sleep, patients are often not aware of them. However, PLMD-associated movements can cause a person to wake up and therefore can compound sleep issues in patients who also have restless legs syndrome.

Although most people with restless legs syndrome have periodic limb movement disorder, many with periodic limb movement disorder do not have restless legs syndrome.

Is there a test for restless leg syndrome?

There is no specific diagnostic test for restless leg syndrome. If you think you may have restless legs syndrome, you should schedule an appointment with your doctor. They will perform a thorough history and physical exam to determine what’s causing your symptoms. Other tests and studies may be required to rule out medical conditions presenting with similar symptoms. Until then, you can track your restless legs syndrome symptoms at home using a sleep diary.

If you have restless legs syndrome you may experience these symptoms:

• You have an irresistible urge to move or stretch, often due to uncomfortable sensations in your legs. These sensations are distinct from numbness, or the cramps associated with a charley horse. Rather, patients with restless legs syndrome describe them as twitching, itching, aching, crawling, tingling, or tugging. Symptoms range from uncomfortable to painful. Restless leg syndrome is so-called because sensations are primarily felt in the legs, although up to 57 percent of people may experience similar sensations in their arms. Sensations usually affect both legs, but can appear in just one, or alternate between legs.
• Moving partially or temporarily relieves these sensations. Individuals with restless legs syndrome may find relief from kicking, rubbing, pacing, walking or moving around. Once you stop moving, the sensations may reoccur.
• Symptoms begin or worsen when you are inactive, particularly when you are lying down, sitting, or resting. For example, you may be lying in bed, resting on the couch, or sitting on a plane.
• Your symptoms primarily occur at night, or worsen during the evening and night. It’s common for the morning to be relatively symptom-free, with symptoms worse at night .
• Your symptoms are not caused by another medical or behavioral condition, such as arthritis, leg cramps, or habitual foot tapping.
• Your symptoms disrupt your sleep, cause you distress, or otherwise impair your wellbeing or ability to function normally. Poor sleep is the main reason people seek out care for their restless legs syndrome symptoms, and affects 60 to 90 percent of individuals with restless legs syndrome. In turn, poor sleep can have negative mental, physical, or behavioral impacts that make coping with restless legs syndrome difficult.

If you’ve experienced these symptoms, you should consult a doctor.

Is it possible to have restless legs syndrome symptoms in other areas of the body?

Yes, restless legs syndrome can affect the arms, trunk or even the face.

Can taking vitamin or mineral supplements help my restless legs syndrome symptoms?

If an underlying vitamin deficiency is found to cause your restless legs syndrome, supplementing with iron, vitamin B12 or folate (as directed by your healthcare provider) may reduce or even alleviate your symptoms. Because the use of even moderate amounts of some minerals (such as iron, magnesium, potassium and calcium) can impair your body’s ability to use other minerals or can cause toxicity, you should use mineral supplements only on the advice of your healthcare provider.

Are there things I should avoid if I have restless legs syndrome?

Some medications, foods and other substances are known to cause or increase restless legs syndrome symptoms. Caffeine use may intensify restless legs syndrome symptoms. Caffeine-containing products, including chocolate and caffeinated beverages such as coffee, tea and soft drinks, should be avoided. Alcohol consumption also increases the span or intensity of symptoms for most individuals.

Are there medications that are known to worsen restless legs syndrome symptoms?

Yes. These medications include:

• Some cold and allergy medications that contain older antihistamines (e.g., diphenhydramine) (like Benadryl) found in many cold, allergy and over-the-counter sleep aids
• Antidizziness, antinausea medications (e.g. prochlorperazine or metoclopramide) like Meclizine, Compazine, Phenergan and Reglan
• Antidepressants that increase serotonin (e.g., fluoxetine or sertraline) such as Elavil, Prozac, Lexapro and Effexor
• Psychiatric medications such a haloperidol and phenothiazines that are used to treat bipolar disorders, schizophrenia and other serious disorders

Always be sure that your healthcare provider is aware of all the medicines you are taking, including herbal supplements and over-the-counter medications.

Can children have restless legs syndrome?

Yes. Restless legs syndrome can occur in people of any age including children ¹². While restless legs syndrome is most often diagnosed in middle-aged individuals, adults can usually trace their symptoms back to childhood and often remember hearing things like “those are growing pains” or “quit wiggling so much.” Research suggests that restless legs syndrome affects an estimated 1.5 million children and adolescents in the United States, and confirms that restless legs syndrome and Periodic Limb Movement Disorder are not unique to adulthood.

Researchers believe that many cases of childhood restless legs syndrome may go undetected for a number of reasons. Children can have trouble communicating their experiences, meaning that symptoms may be mistakenly attributed to other causes such as growing pains, motor tics, muscle pain, leg cramps, or sleep apnea. restless legs syndrome also affects sleep, which can cause secondary effects such as hyperactivity or moodiness that are easily mistaken for attention deficit hyperactivity disorder (ADHD). Evidence connecting restless legs syndrome and attention deficit/hyperactivity disorder (ADHD) is growing. For example, parents may observe their child being restless and fidgety in situations where they are required to sit still, such as a classroom or at the movies. Children with restless legs syndrome often find it difficult to stop these compensatory movements, regardless of where they are.

Diagnosis of restless legs syndrome in kids is based on the same criteria that are used for adults, though children may describe their symptoms differently than adults ¹³. When evaluating a child for restless legs syndrome, a doctor may ask them to describe their symptoms in their own words. Some common phrases used by kids with restless legs syndrome to describe their symptoms include “energy in my legs,” “want to run,” “creepy crawlies,” or “boo-boos.”

Children with restless legs syndrome frequently complain of pain, with symptoms that can be soothed by applying heat or cold, leading to potential confusion with growing pains. One way to differentiate the two conditions is to see whether the pain stops using the classic restless legs syndrome remedy of moving the legs.

Doctors may also collect observations of symptoms consistent with restless legs syndrome when the child is sitting or lying down. In addition, they may assess for sleep disturbance, check for periodic limb movements during sleep, or ask if other family members have restless legs syndrome.

Is restless legs syndrome hereditary?

Restless legs syndrome is familial in about 50 percent of affected individuals which is consistent with a genetic origin. It also may be idiopathic (unknown) or related to acquired conditions such as iron deficiency anemia or chronic renal failure. Several predisposing candidate genes have been identified through genome wide association studies.

Restless leg syndrome symptoms

Common signs and symptoms of restless legs syndrome:

• Leg discomfort combined with strong urge to move. Uncomfortable sensations deep within the legs, accompanied by a strong, often irresistible urge to move them.
• Rest triggers the symptoms. The uncomfortable leg sensations start or become worse when you’re sitting, lying down, or trying to relax.
• Symptoms get worse at night. restless legs syndrome typically flares up at night. In more severe cases, the symptoms may begin earlier in the day, but they become much more intense at bedtime.
• Symptoms improve when you walk or move your legs. The relief continues as long as you keep moving.
• Leg twitching or kicking while sleeping. Many people with restless legs syndrome also have periodic limb movement disorder (PLMD), which involves repetitive cramping or jerking of the legs during sleep.
• The symptoms of restless legs syndrome can range from mildly annoying to severely disabling. You may experience the symptoms only once in a while, such as times of high stress, or they may plague you every night. In severe cases of restless legs syndrome, you may experience symptoms in your arms as well as your legs.

People with restless legs syndrome feel the irresistible urge to move, which is accompanied by uncomfortable sensations in their lower limbs that are unlike normal sensations experienced by people without the disorder ². The sensations in their legs are often difficult to define but may be described as aching throbbing, pulling, itching, crawling, or creeping. These sensations less commonly affect the arms, and rarely the chest or head. Although the sensations can occur on just one side of the body, they most often affect both sides. They can also alternate between sides. The sensations range in severity from uncomfortable to irritating to painful.

Because moving the legs (or other affected parts of the body) relieves the discomfort, people with restless legs syndrome often keep their legs in motion to minimize or prevent the sensations. They may pace the floor, constantly move their legs while sitting, and toss and turn in bed.

A classic feature of restless legs syndrome is that the symptoms are worse at night with a distinct symptom-free period in the early morning, allowing for more refreshing sleep at that time. Some people with restless legs syndrome have difficulty falling asleep and staying asleep. They may also note a worsening of symptoms if their sleep is further reduced by events or activity.

Restless legs syndrome symptoms may vary from day to day, in severity and frequency, and from person to person. In moderately severe cases, symptoms occur only once or twice a week but often result in significant delay of sleep onset, with some disruption of daytime function. In severe cases of restless legs syndrome, the symptoms occur more than twice a week and result in burdensome interruption of sleep and impairment of daytime function.

People with restless legs syndrome can sometimes experience remissions—spontaneous improvement over a period of weeks or months before symptoms reappear—usually during the early stages of the disorder. In general, however, symptoms become more severe over time.

People who have both restless legs syndrome and an associated medical condition tend to develop more severe symptoms rapidly. In contrast, those who have restless legs syndrome that is not related to any other condition show a very slow progression of the disorder, particularly if they experience onset at an early age; many years may pass before symptoms occur regularly.

Restless legs syndrome complications

Although restless legs syndrome doesn’t lead to other serious conditions, symptoms can range from barely bothersome to incapacitating. Many people with restless legs syndrome find it difficult to fall or stay asleep. Severe restless legs syndrome can cause marked impairment in life quality and can result in depression. Insomnia may lead to excessive daytime drowsiness, but restless legs syndrome may interfere with napping.

Restless leg syndrome causes

In most cases, the cause of restless legs syndrome is unknown this is called primary or idiopathic restless legs syndrome. Many researchers suspect restless legs syndrome may be caused by an imbalance of the certain neurotransmitter called dopamine, which sends messages to control muscle movement. Considerable evidence suggests that restless legs syndrome is related to a dysfunction in one of the sections of the brain that control movement called the basal ganglia that use the brain chemical dopamine. Dopamine is needed to produce smooth, purposeful muscle activity and movement. Disruption of these pathways frequently results in involuntary movements. Individuals with Parkinson’s disease, another disorder of the basal ganglia’s dopamine pathways, have increased chance of developing restless legs syndrome.

Low iron stores in the brain may also play a role.

Furthermore, restless legs syndrome has a genetic component and can be found in families where the onset of symptoms is before age 40. Specific gene variants have been associated with restless legs syndrome. Evidence indicates that low levels of iron in the brain also may also be responsible for restless legs syndrome.

Restless legs syndrome also appears to be related to or accompany the following factors or underlying conditions:

• end-stage renal disease and hemodialysis
• iron deficiency
• thyroid problems
• alcoholism
• certain medications that may aggravate restless legs syndrome symptoms, such as antinausea drugs (e.g. prochlorperazine or metoclopramide), antipsychotic drugs (e.g., haloperidol or phenothiazine derivatives), antidepressants that increase serotonin (e.g., fluoxetine or sertraline), and some cold and allergy medications that contain older antihistamines (e.g., diphenhydramine)
• use of alcohol, nicotine, and caffeine
• pregnancy, especially in the last trimester; in most cases, symptoms usually disappear within 4 weeks after delivery
• neuropathy (nerve damage)
• neurologic lesions (spinal cord tumors, peripheral nerve lesions, or spinal cord injury)
• varicose veins or trouble with the nerves in the hands or feet
• multiple sclerosis
• Parkinson’s disease.

Sleep deprivation and other sleep conditions like sleep apnea also may aggravate or trigger symptoms in some people. Reducing or completely eliminating these factors may relieve symptoms.

Genetics

Sometimes restless legs syndrome runs in families, especially if the condition starts before age 40. Researchers have identified sites on the chromosomes where genes for restless legs syndrome may be present.

Restless leg syndrome pregnancy

Pregnancy or hormonal changes may temporarily worsen restless legs syndrome signs and symptoms. Some women get restless legs syndrome for the first time during pregnancy, especially during their last trimester. However, symptoms usually disappear after delivery.

Risk factors for restless legs syndrome

Restless legs syndrome usually isn’t related to a serious underlying medical problem. However, it sometimes accompanies other conditions, such as:

• Peripheral neuropathy. This damage to the nerves in the hands and feet is sometimes due to chronic diseases such as diabetes and alcoholism.
• Iron deficiency. Even without anemia, iron deficiency can cause or worsen restless legs syndrome. If you have a history of bleeding from the stomach or bowels, experience heavy menstrual periods, or repeatedly donate blood, you may have iron deficiency.
• Kidney failure. If you have kidney failure, you may also have iron deficiency, often with anemia. When kidneys don’t function properly, iron stores in the blood can decrease. This and other changes in body chemistry may cause or worsen restless legs syndrome.
• Spinal cord conditions. Lesions on the spinal cord as a result of damage or injury have been linked to restless legs syndrome. Having had anesthesia to the spinal cord, such as a spinal block, also increases the risk of developing restless legs syndrome.
• Parkinson’s disease. People who have Parkinson’s disease and take certain medications called dopaminergic agonists have an increased risk of developing restless legs syndrome.

Restless legs syndrome triggers

Sitting or resting are common triggers for restless legs syndrome symptoms. Additionally, some substances can make symptoms worse. These include:

• Alcohol
• Caffeine
• Nicotine
• Medications, including certain drugs used to treat nausea, colds and allergies, and mental health conditions

Incidentally, most of these substances when taken in excess or too close to bedtime can also adversely affect our sleep architecture.

Restless leg syndrome diagnosis

Your doctor will take your medical history and ask for a description of your symptoms. Since there is no specific test for restless legs syndrome, a diagnosis of restless legs syndrome is based on the following criteria established by the International Restless Legs Syndrome Study Group ⁷:

1. You have a strong, often irresistible urge to move the legs, usually but not always accompanied by uncomfortable and unpleasant sensations in the legs;
2. Your symptoms that start or get worse during periods of rest or inactivity, such as lying down or sitting;
3. Your symptoms are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues;
4. Your symptoms only occur or are worse in the evening or night than during the day; and
5. The occurrence of the above symptoms is not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g. myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping)

A recent expert consensus statement outlined several different restless legs syndrome diagnostic categories based on its presenting clinical features and scenarios, with suggested management strategies and approaches ¹⁴:

• Intermittent restless legs syndrome is defined as restless legs syndrome symptoms sufficiently bothersome to require treatment and occurring, on average, less than twice weekly, for which non-pharmacologic or intermittent prescription medications are typically advised.
• Chronic persistent restless legs syndrome constitutes moderately or severely distressing symptoms occurring at least twice weekly requiring daily treatments, most often requiring medications.
• Refractory restless legs syndrome symptoms are unresponsive to first-line monotherapy medications due to incomplete or reduced efficacy, intolerable adverse effects, or evolution of augmentation, which is a worsening of restless legs syndrome symptoms with temporally earlier, increasingly intense, and often geographically ascending characteristics (as further defined and discussed extensively later in this article). Refractory restless legs syndrome symptoms are usually addressed through a revised management approach, which typically involves assessment for iron deficiency with oral or intravenous iron therapy if indicated, as well as consideration of a medication class switch, a newly added adjunctive drug, or in the setting of augmentation, reduction of dopaminergic therapies with or without substitution by non-dopaminergic medications.

Your doctor will focus largely on your descriptions of symptoms, their triggers and relieving factors, as well as the presence or absence of symptoms throughout the day. A neurological and physical exam, plus information from your medical and family history and list of current medications, may be helpful. Individuals may be asked about frequency, duration, and intensity of symptoms; if movement helps to relieve symptoms; how much time it takes to fall asleep; any pain related to symptoms; and any tendency toward daytime sleep patterns and sleepiness, disturbance of sleep, or daytime function.

Blood tests may rule out other conditions such as kidney failure, iron deficiency anemia (which is a separate condition related to iron deficiency), or pregnancy that may be causing symptoms of restless legs syndrome. Blood tests can identify iron deficiencies as well as other medical disorders associated with restless legs syndrome.

In addition, your doctor may refer you to a sleep specialist. This may involve an overnight stay and a study at a sleep clinic if another sleep disorder such as sleep apnea is suspected. Sleep studies such as polysomnography (a test that records the individual’s brain waves, heartbeat, breathing, and leg movements during an entire night) may identify the presence of other causes of sleep disruption (e.g., sleep apnea), which may impact management of the disorder. Periodic limb movement of sleep during a sleep study can support the diagnosis of restless legs syndrome but, again, is not exclusively seen in individuals with restless legs syndrome. However, a diagnosis of restless legs syndrome usually doesn’t require a sleep study.

Diagnosing restless legs syndrome in children may be especially difficult, since it may be hard for children to describe what they are experiencing, when and how often the symptoms occur, and how long symptoms last. Pediatric restless legs syndrome can sometimes be misdiagnosed as “growing pains” or attention deficit disorder.

Restless leg syndrome treatment

The varying clinical presentations of restless legs syndrome have direct clinical relevance toward management including symptom frequency and severity, disease course, and response to therapy.

Before proceeding with restless legs syndrome treatment, experts recommend looking for other conditions that could be causing or aggravating restless legs syndrome symptoms ¹⁵. Common culprits include:

• Sleep deprivation
• Stress
• A sedentary lifestyle
• Obesity
• Alcohol, nicotine, caffeine use
• Pregnancy
• Diabetes
• Sleep-disordered breathing
• Peripheral neuropathy
• Renal insufficiency
• Medication such as antihistamines and certain antidepressants

For many people, addressing these factors may lead to a drastic reduction in restless legs syndrome symptoms. However, if symptoms are still bothersome, or if they interfere with sleep, doctors may advise additional remedies.

If you have restless legs syndrome without an associated medical condition, treatment focuses on lifestyle changes.

Home remedies for restless legs syndrome

Home remedies offer a simple way to improve restless legs syndrome symptoms. Though more research is needed to confirm how effective these methods are, many people with mild to moderate restless legs syndrome symptoms find relief from a combination of the following:

• Try baths and massages. Soaking in a warm bath and massaging the legs can relax the muscles ¹⁶. Some people find relief from restless legs syndrome symptoms after massaging affected areas. However, there is limited scientific evidence supporting the effectiveness of these methods at this time.
• Apply warm or cool packs. Use of heat or cold, or alternating use of the two, may lessen the limb sensations. Response to temperature may vary from person to person.
• Establish good sleep hygiene. Restless legs syndrome can cause sleep loss and fatigue tends to worsen symptoms of restless legs syndrome, so it’s important that you practice good sleep hygiene. Ideally, have a cool, quiet, comfortable sleeping environment; go to bed and rise at the same time daily; and get at least seven hours of sleep nightly.
• Moving your legs. Moving the affected body part usually leads to relief from uncomfortable sensations, though symptoms may return when movement ceases.
• Exercise. Getting moderate regular exercise and stretching may relieve symptoms of restless legs syndrome, but overdoing it or working out too late in the day may intensify symptoms. People with restless legs syndrome should be careful with high-intensity activity, which may cause muscle cramps and stiffness that can exacerbate symptoms. In 2006, a small study found that a combination of moderate aerobic exercise and lower-body resistance training three days a week reduced restless legs syndrome symptom severity by about 50 percent. The study found that it took six weeks to see maximum benefit from the exercise program. In general, people with restless legs syndrome have reported that moderate exercise seems helpful and that strenuous exercise may worsen symptoms.
• Avoid caffeine. Sometimes cutting back on caffeine may help restless legs. Try to avoid caffeine-containing products, including chocolate, coffee, tea and soft drinks, for a few weeks to see if this helps.
• Avoiding tobacco. Nicotine is a stimulant that impairs blood flow to muscles and can make restless legs worse, so it’s best to avoid cigarettes, vaporizers, and e-cigarettes.
  
• Eating a healthy diet. The Restless Legs Syndrome Foundation recommends reducing alcohol, caffeine, sugar, and salt and following a healthy diet rich in vitamins and minerals ¹⁷. In addition to relieving restless legs syndrome symptoms, a healthy diet can help improve sleep quality.
• Manage stress. Restless legs syndrome symptoms get worse when you’re anxious and overwhelmed. Anything you can do to keep stress in check will help, including relaxation techniques such as meditation and deep breathing.
• Consider using a foot wrap or a vibrating pad. A foot wrap specially designed for people with restless legs syndrome puts pressure under the foot and may help relieve your symptoms. You may also find relief using a pad that vibrates on the back of the legs ¹⁸.
• Improve your sleep. The symptoms of restless legs syndrome can make it hard to get to sleep. When you’re sleep deprived, you not only feel terrible, but you’re more vulnerable to stress. Stress and fatigue can worsen restless legs syndrome, making it a vicious cycle, so doing what it takes to get enough sleep is crucial.
  • Try sleeping with a pillow between your legs. It may prevent nerves in your legs from compressing and result in fewer nighttime restless legs syndrome symptoms.
  • Stick to a regular sleep schedule. Support your body’s natural sleep rhythms by going to bed and getting up at the same time every day (including weekends).
  • Optimize your bedroom for sleep. Make sure the room is dark (no lights from electronic devices), quiet, and cool.
  • Wind down with a relaxing bedtime routine. Try curling up in bed with a book, listening to calming music, or taking a hot bath (the heat has the added bonus of relieving restless legs).
  • Power down electronics 1-2 hours before bed. The blue light from screens (TVs, phones, tablets, computers) suppresses sleep-promoting hormones and stimulates your brain.

Researchers have also proposed acupuncture, electrical stimulation, transcranial magnetic stimulation, sclerotherapy for varicose veins, infrared light, yoga, and other methods for relieving restless legs syndrome symptoms ¹⁹.

• Transcutaneous electric nerve stimulation (TENS). Fifteen to 30 minutes of daily TENS therapy (using low-voltage electrical current) appears to help people who experience a lot of muscle spasms. You can purchase a portable, bedside TENS unit online. They are relatively inexpensive and don’t require a prescription.
• Positional release manipulation. A small medical trial in the United Kingdom found that an osteopathic exercise technique known as positional release manipulation could benefit people with restless legs syndrome. Positional release manipulation involves holding different parts of the body in a position that reduces feelings of discomfort and pain.
• According to research published in the Journal of Alternative and Complementary Medicine, women with restless legs syndrome who practiced yoga reduced their symptoms and experienced less stress, an elevated mood, and better sleep habits. However, there is limited research on whether these treatments are effective, and whether the benefits outweigh the risks.

If these aren’t effective, your doctor might prescribe medications. Iron supplementation or medications are usually helpful but no single medication effectively manages restless legs syndrome for all individuals. Trials of different drugs may be necessary. In addition, medications taken regularly may lose their effect over time or even make the condition worse, making it necessary to change medications.

Stretching exercise for restless legs syndrome

Simple stretching can help stop the symptoms of restless legs syndrome in their tracks. Here’s a handful to help you get started:

• Calf stretch – Stretch out your arms so that your palms are flat against a wall and your elbows are nearly straight. Slightly bend your right knee and step your left leg back a foot or two, positioning its heel and foot flat on the floor. Hold for 20 to 30 seconds. Now bend your left knee while still keeping its heel and foot flat on the floor. For a deeper stretch, move your foot back a bit farther. Switch legs and repeat.
• Front thigh stretch – Standing parallel to a wall for balance, grab and pull one of your ankles toward your buttock while keeping the other leg straight. Hold for 20 to 30 seconds. Switch legs and repeat.
• Hip stretch – Place the back of a chair against the wall for support and stand facing the chair. Raise your left foot up and rest it flat on the chair, with your knee bent. (Or try placing your foot on a stair while holding the railing for balance.) Keeping your spine as neutral as possible, press your pelvis forward gently until you feel a stretch at the top of your right thigh. Your pelvis will move forward only a little. Hold for 20 to 30 seconds. Switch legs and repeat.

Medical devices for restless legs syndrome

New attention is being given to the possibility of using medical devices to improve restless legs syndrome symptoms. Similar to the way that moving the legs gives temporary relief, these medical devices aim to reduce discomfort of restless legs syndrome symptoms by providing external stimulation ²⁰.

So far, the Food and Drug Administration (FDA) has approved two medical devices as restless legs syndrome treatments: a compression foot wrap and a vibrating pad. Both are available by prescription and designed for people with moderate to severe restless legs syndrome.

The foot wrap works by applying targeted pressure to the affected area, usually the lower leg or foot ²¹. By contrast, the vibrating pad uses counter-stimulation to mask restless legs syndrome symptoms and improve sleep quality ²². Both devices are considered fairly safe, though they may not be suitable for people with certain underlying health conditions.

Some doctors also recommend using a pneumatic compression device to ease restless legs syndrome symptoms. It’s thought that compression of the veins helps boost circulation and reduce the uncomfortable sensations caused by restless legs syndrome.

Restless legs syndrome medications

Medication is currently considered the gold standard for people with moderate to severe restless legs syndrome ¹¹. Several prescription medications, most of which were developed to treat other diseases, are available to reduce the restlessness in the legs. It may take several trials for you and your doctor to find the right medication or combination of medications that work best for you. To reduce the risk of unpleasant side effects, always work with a doctor to find the medication that’s right for you.

Iron for restless legs

Sometimes, treating an underlying condition, such as iron deficiency, greatly relieves symptoms of restless legs syndrome. Correcting an iron deficiency may involve receiving iron supplementation orally or intravenously. However, take iron supplements only with medical supervision and after your doctor has checked your blood-iron level. Peripheral iron stores (ferritin, transferrin saturation) should be assessed at the time of initial restless legs syndrome diagnosis, and later during the course of chronic management, whenever there is a change in symptom control, especially when there are features of augmentation or overall clinical worsening of symptom frequency or severity, and/or when there is a waning response to previously effective therapy. If iron stores are low, iron-replacement therapy should generally be pursued, either as monotherapy (if symptoms are relatively mild) or in combination with another restless legs syndrome treatment.

If iron-replacement therapy is indicated for a restless legs syndrome, the first-line approach is typically oral iron-replacement therapy. Various oral iron-replacement therapies are available, most commonly ferrous sulfate. Vitamin C aids the absorption of elemental iron from the gastrointestinal tract, often minimizing side effects. Alternatively, a formulation of ferrous fumarate (Vitron C) may be considered, with dosing of 65 mg of elemental iron taken approximately 1 hour before mealtimes to facilitate optimal absorption. Some patients are unable to tolerate oral iron due to gastric upset, nausea, or constipation or are unable to absorb it effectively, particularly when there is concomitant proton-pump inhibitor use for gastroesophageal reflux (which lowers gastric acid, thereby often decreasing iron absorption), or in patients with a history of prior bariatric or other bowel surgeries leading to limited small-bowel iron absorption. Oral iron supplementation may be insufficient for restless legs syndrome patients presenting with severe symptoms, with or without augmentation, since it often takes a prolonged timeframe of weeks or months for resulting efficacy.

In cases when oral iron is not tolerated or effectively absorbed and in patients with severe restless legs syndrome symptoms, the use of intravenous iron-replacement therapy may be considered. Several formulations are available, with best evidence supporting the use of ferric carboxymaltose in single or divided infused total doses of 1000–1500 mg (i.e., either 1000 mg × one infused dose, or two infused doses of 500–750 mg) ²³. Of note, iron deficiency was not a requirement for some of the clinical trials of ferric carboxymaltose for restless legs syndrome. Thus, this therapy may be beneficial for people with restless legs syndrome without low iron (as long as there is no iron overload), although in practice, use is often limited to those with evidence of iron deficiency. Ferric carboxymaltose is expensive and may be difficult to obtain; in these instances, an alternative formulation to consider is low-molecular weight iron dextran (INFeD), with a 1000 mg total dose infused over 1 hour ²⁴. Pre-treatment with acetaminophen, 1 g, and Solu-Medrol, 125–250 mg, can be considered to limit the possibility of anaphylactic reaction. INFeD 25 mg may be administered as a test dose over 15 min, followed by the remaining 975 mg infusion over 45 min to complete a total 1000 mg infused dose. IV iron infusion typically leads to improvement in clinical restless leg symptoms severity within 2 to 4 weeks. Assessment of the serum ferritin after 1 and 3 months to ensure adequate replacement is prudent. If insufficient (i.e., the patient remains with a ferritin < 75 µg/L and/or transferrin saturation < 20–25%), repeat infusion may be considered.

Dopamine agonists

Dopamine agonists (pramipexole, ropinirole, rotigotine) act like dopamine by stimulating molecules on the surface of certain cells that bind with dopamine (dopamine receptors). Rotigotine (Neupro), pramipexole (Mirapex) and ropinirole are approved by the Food and Drug Administration for the treatment of moderate to severe restless legs syndrome symptoms, at least in the short term ²⁵, ²⁶, ²⁷. Dopamine agonists (pramipexole, ropinirole, rotigotine) have been shown to reduce symptoms of restless legs syndrome when they are taken at nighttime. Short-term side effects of these medications are usually mild and include nausea, lightheadedness and fatigue. However, they can also cause impulse control disorders, such as compulsive gambling, and excessive daytime sleepiness with sleep attacks, leading to harmful consequences such as drowsy driving and motor vehicle collisions.

Although dopamine-related medications are effective in managing restless legs syndrome symptoms, long-term use can lead to worsening of the symptoms in many individuals. A growing body of evidence over the last decade has indicated several shortcomings of dopamine agonist therapies due to their adverse event potential. Most significantly, a large proportion of restless legs syndrome patients (40-80% of patients) treated with excessive doses of dopamine agonists develop augmentation syndrome, at a rate of approximately 8% per year for pramipexole ²⁸. Augmentation syndrome represents both a temporal and spatial progression of restless legs syndrome symptoms to an earlier time-of-day of symptom onset (until the symptoms are present around the clock, often with daylong persistence), with growing intensity of symptoms that have a shorter latency to occur following briefer period of daytime and evening rest, becoming highly sleep-disturbing. Over time, the initial evening or bedtime dose can become less effective, the symptoms at night become more intense, and symptoms could begin to spread from the legs to other body regions to affect the arms or trunk, especially the arms. Fortunately, this apparent progression can be reversed by removing the person from all dopamine-related medications.

A second further significant concern of dopaminergic medications is the approximately 15% frequency of impulse-control disorder symptoms (compared with 6–8% in sleep disorder patients not treated with dopamine agonists) including a spectrum of undesired behaviors such as compulsive and financially destructive shopping, obsessive gambling, punding (repetitive aimless hand movements, such as assembly and reassembly of watches or other gadgets), and other quasi-addictive behaviors ²⁹. A common theme of impulse control disorder spectrum behaviors is an inability to control impulses toward undesirable behaviors, often leading to socially destructive consequences. Should they occur, these behaviors can be improved or reversed by stopping the medication.

Pramipexole (Mirapex) is started at a dose of 0.125 mg administered approximately 1 to 2 hour prior to bedtime (or typical symptom onset, if symptoms begin before bed) ¹. Pramipexole may then be further titrated by 0.125 mg every 3 to 7 days, toward a target dose in the range of 0.375 to 0.5 mg at maximum for the day, using the lowest effective dosage for symptom control. Some patients require divided doses, in the afternoon and prior to bedtime, if symptoms begin earlier in the afternoon. The maximal pramipexole dose range of 0.5 mg/day should only rarely be exceeded, due to the increased risk of augmentation syndrome at higher doses ³⁰. However, some experts advise further titration over the dose range of 0.5 to 1.0 mg total daily dose with careful serial observation and repeated counseling to instruct patients to immediately report earlier or more intense symptoms ³⁰.

An alternative is ropinirole (Requip), with initial doses of 0.25 mg, increasing by 0.25 to 0.5 mg increments to the dose range of 3.0 to 4.0 mg maximal daily dose. However, some experts will consider more aggressive dosing in the daily dose range of 4.0 to 6.0 mg with similar careful observation and adequate counseling of the patient.

The rotigotine (Neupro) patch can provide daylong symptom control for the patient, given its continual gradual daylong release ³¹. This prolonged duration of action and more continual release of dopamine into the bloodstream may minimize dopamine fluctuation at receptors and may be associated with a lower tendency toward evolving augmentation syndrome ³². Rotigotine dosing may be started at a 1.0 mg patch strength and titrated weekly to either 2 or 3 mg maximal daily dose ³⁰. The clinical trials of rotigotine suggested that further dose increases to 4.0 mg daily may be considered, but there may be greater augmentation risk at this higher dose ³³. Rotigotine as a transdermal patch may cause cutaneous reactions such as excessive itching or redness of the skin underlying the site of patch application. However, this may be avoided or minimized by rotation of the patch location on a daily basis. Optimal places for patch location include sites along the upper outer arms, upper legs, the scapula, or upper back. Otherwise, the range of adverse effects is similar to the other dopaminergic therapies. Expense has been a limiting factor in the more widespread application of this dopaminergic therapy.

Levodopa

Levodopa also known as L-dopa, is a dopamine precursor that increases concentrations of dopamine in the brain. Because certain enzymes immediately begin to break down available dopamine, a medication (carbidopa) that blocks the activity of such enzymes is often combined with L-dopa (e.g., as a combination drug known as carbidopa-levodopa [Sinemet]). Many individuals who take levodopa medications may develop more severe restless legs syndrome symptoms when the dose begins to wear off, or earlier in the day before treatment was initiated (known as “augmentation”). Because of this, the drug should never be used long-term but should be restricted to intermittent use, not more frequently than twice a week.

Carbidopa levodopa (Sinemet) may still be useful in the occasional patient with infrequent symptoms for which intermittent medication treatment can be considered. Sinemet should be avoided in patients with daily disturbing restless legs syndrome symptoms; approximately 60% of patients will experience augmentation syndrome within 6 months of treatment when carbidopa levodopa is given daily ³⁴. However, it can be useful in treating restless legs syndrome in the patient with occasional symptoms, such as those who experience symptoms during flights or long car rides. If patients find this medication to be sedating, they should be counseled not to use it prior to driving.

Drugs affecting calcium channels

Certain anti-seizure drugs, such as gabapentin (Neurontin, Gralise), gabapentin enacarbil (Horizant) and pregabalin (Lyrica), work for some people with restless legs syndrome. Gabapentin and related medications (gabapentin enacarbil, pregabalin [Lyrica]) have recently become preferred first-line medications for restless legs syndrome management ¹⁵. The FDA has approved gabapentin enacarbil (Horizant) for the treatment of moderate to severe restless legs syndrome. This drug appears to be as effective as dopamine agonists treatment and, at least to date, there have been no reports of problems with a progressive worsening of symptoms due to medication (called augmentation). Other medications may be prescribed “off-label” to relieve some of the symptoms of restless legs syndrome. Other anti-seizure drugs such as the standard form of gabapentin (Neurontin, Gralise) and pregabalin (Lyrica) can decrease such sensory disturbances as creeping and crawling as well as nerve pain. Typical side effects of gabapentin, gabapentin enacarbil, and pregabalin include sleepiness, drowsiness, dizziness, and unsteadiness, so caution must be taken in elderly patients to avoid the risk of instability and falls. Driving impairment may occur. Providers also must use prudence with patients with chronic renal insufficiency, since these medications can accumulate due to reduced renal clearance. In such patients, starting with lower-end doses and titrating toward a lower target dose is advised. Other typical adverse effects with gabapentin include peripheral edema and weight gain. A similar range of adverse effects are seen in gabapentin enacarbil and pregabalin.

Gabapentin may be started at doses of 100 to 300 mg, 1 to 2 hours in advance of evening symptoms, and can be given in divided doses throughout the daytime depending on whether patients have late-afternoon or early-evening symptoms (i.e., given twice daily, thrice daily, or four times daily, individualizing to the patients symptoms and perceived duration of action). The doses are then advanced by 100- to 300-mg increments as needed and tolerated, typically every 3 to 7 days, toward a broad target dosage of 600 to 2400 mg nightly, which was rigorously analyzed in an early proof of concept, randomized, double-blind, placebo-controlled crossover trial which showed a mean effective gabapentin dose of 1855 mg/day and the effective dose ranging from 1391 to 2400 mg/day ³⁵. Another limitation of gabapentin is that higher range doses (i.e., above 1800 mg/day) are poorly absorbed, since the drug is absorbed by a saturable intestinal L-amino acid transporter. Therefore, smaller, more frequent doses must be given to permit adequate absorption, through the dose range of 1800 to 3600 mg daily, although dosages substantially above 2400 mg are even more poorly absorbed despite multiple daily doses. For patients responsive to and able to tolerate gabapentin but requiring higher doses to achieve efficacy, pregabalin (Lyrica) may be especially valuable to consider, since there is no dose-limited absorption of this medication and it works mechanistically similarly to gabapentin. Sound evidence exists for efficacy of pregabalin in restless legs syndrome. A pivotal, randomized, controlled trial compared the efficacy of pregabalin to pramipexole and found that doses of pregabalin in the range of 300 mg daily offered comparable or superior efficacy to pramipexole but with a lower incidence of augmentation syndrome.

Opioids

Narcotic medications are used mainly to relieve severe symptoms and are typically reserved for patients who have failed other medications, but they may be addicting if used in high doses. Some examples include tramadol (Ultram, ConZip), codeine, oxycodone (Oxycontin, Roxicodone, others) and hydrocodone (Hysingla ER).

Initial use of lower-potency opioid agents and later escalation toward higher-potency opioids is the preferred approach in chronic severe restless legs syndrome symptom management unless the patient has particularly severe symptoms or advanced augmentation syndrome, which may necessitate escalation to higher-potency opioids. Tramadol, 50 to 200 mg nightly, rarely exceeding and titrating further to 300 or 400 mg as the maximal daily dosage, is often the initial lower-potency opioid used for treating restless legs syndrome. When symptoms begin earlier in the daytime (i.e., in the early evening, afternoon hours, or earlier), a strategy of split multiple daily doses divided between a 6- and 8-hour dosing interval may be employed. Typical adverse effects include sleepiness, drowsiness, or dizziness. Nausea or gastric upset may also occur. Tramadol may be especially useful in patients with concurrent chronic neuropathic pain.

The next intermediate-potency opioid agent to treat restless legs syndrome is oxycodone, in initial doses of 5 to 10 mg, titrating by 5- to 10-mg increments in nightly doses 1 hour before symptom onset. Alternatively, patients with earlier daytime symptoms may divide the doses 2 or 3 times daily on a schedule of every 6 to 12 hours. The range of adverse effects is similar to those outlined above, with more prominent nausea, gastric upset, and constipation occurring with oxycodone.

Higher-potency opioids, particularly methadone, have been utilized with good success as a “last resort” in the treatment of particularly severe and intense restless legs syndrome symptoms, often in the setting of augmentation syndrome caused by high dosage dopaminergic medications ³⁶. In such settings, rapid weaning of the dopaminergic drug and replacing it with methadone may be the best strategy for select patients with severe restless legs syndrome symptoms, with careful oversight. Patients require significant counseling regarding the stigma of methadone, as it is often used in the setting of heroin detoxification and advanced cancer pain. Methadone has the advantage of a particularly long duration of action, but this also carries an inherent risk for overdose ³⁷. Initial doses of 5 mg daily, titrating by 2.5- to 5-mg increments as needed and tolerated toward a total daily dosage of 20 to 30 mg daily is the usual strategy ³⁸. As above, doses may be divided, typically in 12-hour intervals as a twice-daily dose strategy for patients with daylong severe restless legs syndrome symptoms. After augmentation symptoms have been controlled for a few weeks to months, the methadone dose can be lowered to the lowest effective dosing level. In addition to usual adverse effects of sedation, nausea or constipation, distinctive adverse effects seen with methadone include hyperhidrosis, which is sometimes intolerable, and the potential for QTc prolongation and severe ventricular cardiac arrhythmias including ventricular tachycardia, torsade de pointe, or fibrillation ³⁹. Therefore, baseline ECG and serial monitoring of electrocardiograms are recommended both during titration and once the patient has reached an effective target dose to assure safety of continued treatment. If the patient is receiving other QTc-prolonging medications, there may be a particular danger of precipitating cardiac arrhythmias, so discontinuation of other QTc-prolonging drugs is recommended prior to initiating methadone. The concomitant use of benzodiazepines with opioids also should be avoided. Discontinuation of benzodiazepine medications should occur prior to opioid use to avoid respiratory depression. Treatment of co-morbid sleep-disordered breathing with nasal positive airway-pressure therapies is also essential when opioids are used to prevent worsening of obstructive or central sleep apnea. In particular, chronic opioid use has been associated with central sleep apnea and ataxic breathing ⁴⁰. For this reason, patients receiving opioid medications should be evaluated for possible sleep-disordered breathing and undergo a polysomnogram or home sleep apnea test study if there is a concern for co-morbid sleep apnea.

Muscle relaxants and sleep medications

Benzodiazepines can help individuals obtain a more restful sleep at night, but they don’t eliminate the leg sensations, and they may cause daytime drowsiness. However, even if taken only at bedtime they can sometimes cause daytime sleepiness, reduce energy, and affect concentration. Benzodiazepines such as clonazepam and lorazepam are generally prescribed to treat anxiety, muscle spasms, and insomnia. Because these drugs also may induce or aggravate sleep apnea in some cases, they should not be used in people with this condition. These are last-line drugs due to their side effects and only used if no other treatment provides relief.

Caution about medications

Sometimes dopamine medications that have worked for a while to relieve your restless legs syndrome become ineffective, or you notice your symptoms returning earlier in the day or involving your arms. This is called augmentation. Your provider may substitute another medication to combat the problem.

Most drugs prescribed to treat restless legs syndrome aren’t recommended during pregnancy. Instead, your provider may recommend self-care techniques to relieve symptoms. However, if the sensations are particularly bothersome during your last trimester, your provider may approve the use of certain drugs.

Some medications may worsen symptoms of restless legs syndrome. These include some antidepressants, some antipsychotic medications, some anti-nausea drugs, and some cold and allergy medications. Your provider may recommend that you avoid these drugs, if possible. However, if you need to take these medications, talk to your provider about adding drugs to help manage your restless legs syndrome.

Restless legs syndrome and nutrition

Many cases of restless legs syndrome are associated with iron deficiency, which can be treated with iron supplements ⁴¹. These have few side effects apart from stomach complaints and constipation, and they work to reduce symptoms of restless legs syndrome in many people with low iron and ferritin levels or iron-deficiency anemia. After checking your iron and ferritin levels, your doctor may prescribe iron supplements alone or in conjunction with other medications.

Other vitamins and minerals such as magnesium ⁴², zinc ⁴³ and vitamin D ⁴⁴ may also play a role in restless legs syndrome.

• Magnesium can improve sleep and some studies have shown it to be beneficial for restless legs. Try experimenting with a magnesium supplement (250 to 500 mg) at bedtime to see if your symptoms improve.
• Vitamin D. Recent studies show that restless legs syndrome symptoms are more frequent and more severe in people with vitamin D deficiency. Your doctor can easily test your vitamin D levels or you can simply make it a point to get out more in the sun.

Pregnant women in particular may benefit from folate supplements ⁸. Folate deficiency has been linked to restless legs syndrome, which may explain why restless legs are so common in pregnant women (folate plays a key role in healthy fetal development). When folic acid is low, vitamin B12 is often low as well, so you may want to try supplementing with a B-complex vitamin.

People with kidney problems may benefit from vitamin C and vitamin E supplements ⁴⁵.

Restless leg syndrome prognosis

Restless legs syndrome is generally a lifelong condition for which there is no cure ². However, current therapies can control the disorder, minimize symptoms, and increase periods of restful sleep. Restless legs syndrome symptoms tend to get worse over time and with age, although the decline may be somewhat faster for individuals who also suffer from an associated medical condition. Restless legs syndrome may begin in childhood and develop slowly over several years. People with early symptoms are more likely to have other family members with restless legs syndrome than people who develop restless legs syndrome later in life. In addition, some individuals have remissions—periods in which symptoms decrease or disappear for days, weeks, months, or years—although symptoms often eventually reappear. If restless legs syndrome symptoms are mild, do not produce significant daytime discomfort, or do not affect an individual’s ability to fall asleep, the condition does not have to be treated.

A diagnosis of restless legs syndrome does not indicate the onset of another neurological disease, such as Parkinson’s disease. However, restless legs syndrome that occurs later in life is also more likely to result from an underlying condition or illness than restless legs syndrome that occurs early in life. Symptoms tend to worsen faster when restless legs syndrome occurs later in life.

Coping and support

Restless legs syndrome is generally a lifelong condition. It may help you to develop coping strategies that work for you, such as:

• Learning to recognize and avoid your personal triggers can help you manage restless legs syndrome over time.
• Effective techniques for minimizing restless legs syndrome symptoms vary from person to person ¹⁶. Many people find relief from keeping active throughout the day and using acupuncture, massage, stretching, or relaxation techniques at night. During the day, you may be able to ward off restless legs syndrome symptoms by keeping your mind busy even when you are sitting still with activities like reading or chatting to a friend.
• Tell others about your condition. Sharing information about restless legs syndrome will help your family members, friends and co-workers better understand when they see you pacing the halls, standing at the back of the theater or walking to the water cooler many times throughout the day.
• Don’t resist your need for movement. If you attempt to suppress the urge to move, you may find that your symptoms worsen.
• Keep a sleep diary. Though restless legs syndrome is not life-threatening, the frustration of not being able to sleep well can take a toll on mental health. Keep track of the medications and strategies that help or hinder your battle with restless legs syndrome, and share this information with your doctor.
• Stretch and massage. Begin and end your day with stretching exercises or gentle massage.
• Seek help. Cognitive behavioral therapy, support groups, or reaching out to family and friends may provide additional emotional resources for coping with restless legs syndrome. By participating in a group, your insights not only can help you but also may help someone else.

1. Gossard, T. R., Trotti, L. M., Videnovic, A., & St Louis, E. K. (2021). Restless Legs Syndrome: Contemporary Diagnosis and Treatment. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 18(1), 140–155. https://doi.org/10.1007/s13311-021-01019-4[↩][↩][↩]
2. Restless Legs Syndrome Fact Sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Restless-Legs-Syndrome-Fact-Sheet[↩][↩][↩]
3. Mansur A, Castillo PR, Rocha Cabrero F, et al. Restless Legs Syndrome. [Updated 2021 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430878[↩]
4. Holzknecht, E., Hochleitner, M., Wenning, G. K., Högl, B., & Stefani, A. (2020). Gender differences in clinical, laboratory and polysomnographic features of restless legs syndrome. Journal of sleep research, 29(3), e12875. https://doi.org/10.1111/jsr.12875[↩]
5. Sharon D, Allen RP, Martinez-Martin P, Walters AS, Ferini Strambi L, Högl B, Trotti LM, Buchfuhrer M, Swieca J, Bogan RK, Zak R, Hensley JG, Schaefer LA, Marelli S, Zucconi M, Stefani A, Holzknecht E, Olvera V, Meaklim H, Laska I, Becker PM; International RLS Study Group. Validation of the self-administered version of the international Restless Legs Syndrome study group severity rating scale – The sIRLS. Sleep Med. 2019 Feb;54:94-100. doi: 10.1016/j.sleep.2018.10.014[↩]
6. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003 Mar;4(2):121-32. doi: 10.1016/s1389-9457(02)00258-7[↩]
7. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB; International Restless Legs Syndrome Study Group. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep Med. 2014 Aug;15(8):860-73. doi: 10.1016/j.sleep.2014.03.025[↩][↩]
8. Srivanitchapoom, P., Pandey, S., & Hallett, M. (2014). Restless legs syndrome and pregnancy: a review. Parkinsonism & related disorders, 20(7), 716–722. https://doi.org/10.1016/j.parkreldis.2014.03.027[↩][↩]
9. Darvishi, N., Daneshkhah, A., Khaledi-Paveh, B., Vaisi-Raygani, A., Mohammadi, M., Salari, N., Darvishi, F., Abdi, A., & Jalali, R. (2020). The prevalence of Restless Legs Syndrome/Willis-ekbom disease (RLS/WED) in the third trimester of pregnancy: a systematic review. BMC neurology, 20(1), 132. https://doi.org/10.1186/s12883-020-01709-0[↩]
10. Trenkwalder C, Beneš H, Grote L, García-Borreguero D, Högl B, Hopp M, Bosse B, Oksche A, Reimer K, Winkelmann J, Allen RP, Kohnen R; RELOXYN Study Group. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol. 2013 Dec;12(12):1141-50. doi: 10.1016/S1474-4422(13)70239-4. Epub 2013 Oct 18. Erratum in: Lancet Neurol. 2013 Dec;12(12):1133.[↩]
11. Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS). https://www.msdmanuals.com/professional/neurologic-disorders/sleep-and-wakefulness-disorders/periodic-limb-movement-disorder-plmd-and-restless-legs-syndrome-rls[↩][↩]
12. Maheswaran, M., & Kushida, C. A. (2006). Restless legs syndrome in children. MedGenMed : Medscape general medicine, 8(2), 79. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785221[↩]
13. Picchietti DL, Bruni O, de Weerd A, Durmer JS, Kotagal S, Owens JA, Simakajornboon N; International Restless Legs Syndrome Study Group (IRLSSG). Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study Group. Sleep Med. 2013 Dec;14(12):1253-9. doi: 10.1016/j.sleep.2013.08.778[↩]
14. Silber MH, Becker PM, Earley C, Garcia-Borreguero D, Ondo WG; Medical Advisory Board of the Willis-Ekbom Disease Foundation. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc. 2013 Sep;88(9):977-86. doi: 10.1016/j.mayocp.2013.06.016[↩]
15. Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge J, Buchfuhrer M, Hadjigeorgiou G, Inoue Y, Manconi M, Oertel W, Ondo W, Winkelmann J, Allen RP. Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med. 2016 May;21:1-11. doi: 10.1016/j.sleep.2016.01.017[↩][↩]
16. Mitchell U. H. (2011). Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatric disease and treatment, 7, 251–257. https://doi.org/10.2147/NDT.S19177[↩][↩]
17. Restless Legs Syndrome Foundation Blog. https://rlsfoundation.blogspot.com/2020/04/eating-with-rls.html[↩]
18. Lettieri CJ, Eliasson AH. Pneumatic compression devices are an effective therapy for restless legs syndrome: a prospective, randomized, double-blinded, sham-controlled trial. Chest. 2009 Jan;135(1):74-80. doi: 10.1378/chest.08-1665[↩]
19. Park, A., Ambrogi, K., & Hade, E. M. (2020). Randomized pilot trial for the efficacy of the MMF07 foot massager and heat therapy for restless legs syndrome. PloS one, 15(4), e0230951. https://doi.org/10.1371/journal.pone.0230951[↩]
20. Rozeman, A. D., Ottolini, T., Grootendorst, D. C., Vogels, O. J., & Rijsman, R. M. (2014). Effect of sensory stimuli on restless legs syndrome: a randomized crossover study. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 10(8), 893–896. https://doi.org/10.5664/jcsm.3964[↩]
21. https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN110009.pdf[↩]
22. https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN110011.pdf[↩]
23. Trotti, L. M., & Becker, L. A. (2019). Iron for the treatment of restless legs syndrome. The Cochrane database of systematic reviews, 1(1), CD007834. https://doi.org/10.1002/14651858.CD007834.pub3[↩]
24. Cho YW, Allen RP, Earley CJ. Lower molecular weight intravenous iron dextran for restless legs syndrome. Sleep Med. 2013 Mar;14(3):274-7. doi: 10.1016/j.sleep.2012.11.001[↩]
25. Trenkwalder C, Benes H, Grote L, Happe S, Högl B, Mathis J, Saletu-Zyhlarz GM, Kohnen R; CALDIR Study Group. Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. Mov Disord. 2007 Apr 15;22(5):696-703. doi: 10.1002/mds.21401[↩]
26. Benes H, Kurella B, Kummer J, Kazenwadel J, Selzer R, Kohnen R. Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial. Sleep. 1999 Dec 15;22(8):1073-81. doi: 10.1093/sleep/22.8.1073[↩]
27. Micozkadioglu H, Ozdemir FN, Kut A, Sezer S, Saatci U, Haberal M. Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: an open-label study. Ren Fail. 2004 Jul;26(4):393-7. doi: 10.1081/jdi-120039823[↩]
28. Allen RP, Chen C, Garcia-Borreguero D, Polo O, DuBrava S, Miceli J, Knapp L, Winkelman JW. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med. 2014 Feb 13;370(7):621-31. doi: 10.1056/NEJMoa1303646[↩]
29. Cornelius, J. R., Tippmann-Peikert, M., Slocumb, N. L., Frerichs, C. F., & Silber, M. H. (2010). Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study. Sleep, 33(1), 81–87.[↩]
30. Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, Salminen AV, Winkelman JW, Trenkwalder C, Sampaio C. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017)§. Mov Disord. 2018 Jul;33(7):1077-1091. doi: 10.1002/mds.27260[↩][↩][↩]
31. Garcia-Borreguero D, Allen R, Hudson J, Dohin E, Grieger F, Moran K, Schollmayer E, Smit R, Winkelman J. Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study. Curr Med Res Opin. 2016;32(1):77-85. doi: 10.1185/03007995.2015.1103216[↩]
32. Trenkwalder C, Benes H, Poewe W, Oertel WH, Garcia-Borreguero D, de Weerd AW, Ferini-Strambi L, Montagna P, Odin P, Stiasny-Kolster K, Högl B, Chaudhuri KR, Partinen M, Schollmayer E, Kohnen R; SP790 Study Group. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2008 Jul;7(7):595-604. doi: 10.1016/S1474-4422(08)70112-1[↩]
33. Oertel W, Trenkwalder C, Beneš H, Ferini-Strambi L, Högl B, Poewe W, Stiasny-Kolster K, Fichtner A, Schollmayer E, Kohnen R, García-Borreguero D; SP710 study group. Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. Lancet Neurol. 2011 Aug;10(8):710-20. doi: 10.1016/S1474-4422(11)70127-2[↩]
34. García-Borreguero D, Kohnen R, Högl B, Ferini-Strambi L, Hadjigeorgiou GM, Hornyak M, de Weerd AW, Happe S, Stiasny-Kolster K, Gschliesser V, Egatz R, Cabrero B, Frauscher B, Trenkwalder C, Hening WA, Allen RP. Validation of the Augmentation Severity Rating Scale (ASRS): a multicentric, prospective study with levodopa on restless legs syndrome. Sleep Med. 2007 Aug;8(5):455-63. doi: 10.1016/j.sleep.2007.03.023[↩]
35. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002 Nov 26;59(10):1573-9. doi: 10.1212/wnl.59.10.1573[↩]
36. Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord. 2005 Mar;20(3):345-8. doi: 10.1002/mds.20359[↩]
37. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother. 2005;19(4):13-24.[↩]
38. Silver N, Allen RP, Senerth J, Earley CJ. A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome. Sleep Med. 2011 May;12(5):440-4. doi: 10.1016/j.sleep.2010.11.002[↩]
39. Mujtaba, S., Romero, J., & Taub, C. C. (2013). Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?. Journal of cardiovascular disease research, 4(4), 229–235. https://doi.org/10.1016/j.jcdr.2013.10.001[↩]
40. Filiatrault, M. L., Chauny, J. M., Daoust, R., Roy, M. P., Denis, R., & Lavigne, G. (2016). Medium Increased Risk for Central Sleep Apnea but Not Obstructive Sleep Apnea in Long-Term Opioid Users: A Systematic Review and Meta-Analysis. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 12(4), 617–625. https://doi.org/10.5664/jcsm.5704[↩]
41. Aurora, R. N., Kristo, D. A., Bista, S. R., Rowley, J. A., Zak, R. S., Casey, K. R., Lamm, C. I., Tracy, S. L., Rosenberg, R. S., & American Academy of Sleep Medicine (2012). The treatment of restless legs syndrome and periodic limb movement disorder in adults–an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep, 35(8), 1039–1062. https://doi.org/10.5665/sleep.1988[↩]
42. Marshall NS, Serinel Y, Killick R, Child JM, Raisin I, Berry CM, Lallukka T, Wassing R, Lee RW, Ratnavadivel R, Vedam H, Grunstein R, Wong KK, Hoyos CM, Cayanan EA, Comas M, Chapman JL, Yee BJ. Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder: A systematic review. Sleep Med Rev. 2019 Dec;48:101218. doi: 10.1016/j.smrv.2019.101218[↩]
43. Chen, P., Bornhorst, J., Patton, S., Bagai, K., Nitin, R., Miah, M., Hare, D. J., Kysenius, K., Crouch, P. J., Xiong, L., Rouleau, G. A., Schwerdtle, T., Connor, J., Aschner, M., Bowman, A. B., & Walters, A. S. (2021). A potential role for zinc in restless legs syndrome. Sleep, 44(4), zsaa236. https://doi.org/10.1093/sleep/zsaa236[↩]
44. Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Neurochemical features of idiopathic restless legs syndrome. Sleep Med Rev. 2019 Jun;45:70-87. doi: 10.1016/j.smrv.2019.03.006[↩]
45. Sagheb MM, Dormanesh B, Fallahzadeh MK, Akbari H, Sohrabi Nazari S, Heydari ST, Behzadi S. Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial. Sleep Med. 2012 May;13(5):542-5. doi: 10.1016/j.sleep.2011.11.010[↩]