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An Academic Research Center of Excellence
march - april
2008
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Restless Legs Syndrome:
A Not So Moving Experience
R
estless legs syndrome (RLS) can be described as a neurologic sensory motor disorder characterized by an overwhelming urge to move the legs when they are at rest. This involuntary need to move the legs may be accompanied by a variety of other unpleasant sensations. RLS affects approximately 10% of adults—nearly 12 million people—in the United States. The syndrome is commonly misdiagnosed as insomnia or other neurologic condition. The urge to move the legs usually occurs upon inactivity and is temporarily relieved by either movement or pressure. The most severe symptoms of RLS occur in the evening and nighttime hours and can significantly disrupt normal sleep and the patient’s quality of life. RLS is often seen in other family members and appears to have a strong genetic basis. The syndrome usually occurs in adults, but has been reported in all age groups. It is slightly more common in women. In children, RLS can be confused with growing pains or restlessness. Older patients often experience similar symptoms of restlessness; however, they increase in frequency and severity over time and with age. This condition is generally categorized into two forms, primary and secondary. Primary RLS is unrelated to any other disorder or condition, whereas the secondary form may be associated with a number of other common diseases or medications. Nearly 40-60% of the cases of RLS are of the primary variety.
Signs and Symptoms The major symptom associated with RLS is an uncomfortable sensation that results in an irresistible urge to move the legs. These sensations usually occur between the knee and ankle and can occur whether sitting or lying down. Symptoms are less common in the arms, face, torso, and genital region. The feelings are often described as creeping, itching, aching, burning, etc. Symptoms generally occur on both sides of the body; however, it is possible they only affect one side. People often find relief by moving the legs.
From: DaVita Online Network http://www.davita.com/kidney-disease/complications/a/895 (accessed 31 January 2008)
In general, there is little difference in symptoms between the primary and secondary forms of RLS. Pacing the floor, tossing and turning in bed, and constantly moving the legs while at rest provide some measure of relief. Patients relying on these methods to abort symptoms should see their physician for proper diagnosis and treatment.
Causes of RLS As stated earlier, the primary form of RLS has no known cause. Secondary RLS may be due to underlying conditions such as low iron levels (with or without anemia), chronic diseases (for example kidney failure, diabetes, Parkinson’s disease, rheumatoid arthritis, etc.), existing nerve damage in the hands and/or feet, third-semester pregnancy, etc. Some medications used to treat nausea, seizures, nasal congestion, and psychiatric disorders have been associated with symptoms similar to RLS. In addition, caffeine, alcohol, and tobacco may trigger an exacerbation or flare of symptoms.
Diagnosis There are no specific tests for diagnosing RLS. Diagnosis is based solely on the patient’s medical history and clinical symptoms. continued on back
restless legs syndrome: A Not So Moving Experience Because the physician must rely heavily on the patient’s description of the problem, RLS is often misdiagnosed. At the time of physical exam and review of the medical history, the physician should address certain topics to assist in diagnosis. These include identifying general sleep habits, frequency of symptoms, general quality of life, and other medical conditions. The International Restless Legs Syndrome Study Group identified criteria for properly diagnosing RLS in 1995. These include a constant need to move the extremities, symptoms that worsen or appear while at rest and are alleviated upon movement, motor restlessness, and an increased severity of symptoms at night. Specific laboratory tests may be performed in order to rule out conditions such as anemia, renal insufficiency, diabetes, etc. that may be the cause of secondary RLS. Ultrasound and other studies may be conducted to determine the amount of activity within muscle and nerves.
Prognosis There is no cure for RLS; however, drug therapy and appropriate lifestyle changes can result in resolution of symptoms. Even though RLS is a lifelong condition, patients may experience periods of remission that extend for days to months. In some cases, the symptoms may be so severe as to be debilitating.
Treatment
Once diagnosed, patients can be treated using lifestyle modification and/or drug therapy. A summary of the prescription drugs used in RLS is included in the accompanying table. Lifestyle Modification: Initiating lifestyle changes is the first approach in treating RLS. They include moderate exercise, decreased stress, massage therapy, improved sleep habits and avoidance of the triggers discussed previously. Patients should continue these changes in daily life even if placed on prescription therapy. Dopamine Agonists: Dopamine is a neurotransmitter found within the brain. Increased dopamine activity results in a decrease in the sensory perceptions associated with RLS. Two drugs, pramipexole (Mirapex) and ropinirole (Requip), bind to dopamine receptors in the brain and increase dopamine activity. They are the only FDAapproved medications for treating RLS. Dopamine Precursor: Levodopa is converted in the body to dopamine and is occasionally used as initial therapy for mild cases of RLS.
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Opioids: These medications bind to opioid receptors found within the central nervous system and help to decrease pain. In RLS, opioids help to relax the patient and decrease any painful sensations they may be experiencing. Anticonvulsants: This group of drugs decreases sensory effects by reducing excessive activity of neurons within the brain. As activity decreases, the symptoms of tingling and aching are alleviated. RLS can affect the quality of life in all patients suffering from the disease. Lifestyle changes, the use of prescription drugs, and referral to appropriate support groups can greatly reduce symptoms and help the patient cope with the condition.
class
drug
Dopamine agonists
pramipexole (Mirapex) ropinirole (Requip)
Only medications FDA approved to treat RLS; reserved for treatment of moderate to severe cases
Dopamine precursors
levodopa
Increases motor function; refrain from long-term use due to adverse effects; often used in conjunction with carbidopa
Benzodiazepines
clonazepam (Klonopin) diazepam (Valium)
Use only to enhance sleep; does not relieve RLS symptoms; may cause daytime sleepiness
Opioids
codeine oxycodone (Oxycontin) propoxyphene (Darvon)
Induce relaxation and reduce pain; may cause dizziness, nausea, and vomiting
Anticonvulsants
carbamazepine (Tegretol) gabapentin (Neurontin) valproic acid (Depakote)
Decrease sensory effects (tingling, aching); improve sleep; may cause dizziness and fatigue
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A publication of: Mylan School of Pharmacy Center for Pharmacy Care Pharmaceutical Information Center (PIC)
Benzodiazepines: This class of medications is used primarily to help the patient sleep. They have no direct affect on other symptoms associated with this condition.
Drugs Used in the Treatment of Restless Legs Syndrome
There are three main goals in RLS treatment: • Relieving symptoms • Increasing the quality and amount of sleep • Treating or correcting any underlying condition(s) responsible for secondary RLS
Because of possible adverse effects, levodopa is normally not used on a long-term basis.
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Newsletter Contributors
For more information on Restless Leg Syndrome, visit the following Web sites:
John G. Lech, Pharm.D. Amanda M. Strutt, Pharm.D. Candidate Brian P. Matthews, Pharm.D. Candidate
• http://www.ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm
• http://www.rls.org • http://www.wemove.org/rls/rls_dor.html 319363 2/08