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Restless Legs Syndrome Medication

  • Author: Ali M Bozorg, MD; Chief Editor: Selim R Benbadis, MD  more...
Updated: Apr 15, 2016

Medication Summary

Medications used in the treatment of restless legs syndrome (RLS) include the following:

  • Dopaminergic agents
  • Benzodiazepines
  • Opioids
  • Anticonvulsants
  • Alpha 2 -adrenergic agonists
  • Iron salt

Antiparkinson Agents, Dopamine Agonists

Class Summary

Dopamine agonists may improve sensory symptoms associated with RLS. Agents such as pramipexole, ropinirole, and bromocriptine are less likely to produce augmentation or rebound than the combination of levodopa and carbidopa is. These agents can be used alone or along with levodopa.

Pramipexole (Mirapex, Mirapex ER)


Pramipexole is a dopamine D2- and D3-receptor agonist that has been approved by the US Food and Drug Administration (FDA) for the treatment of Parkinson disease. It is also used effectively in patients with RLS.

Ropinirole (Requip, Requip XL)


Ropinirole is a dopamine D2-receptor agonist that has been approved by the FDA for the treatment of Parkinson disease. It has also has been used in patients with RLS. Ropinirole is a nonergoline, nonphenolic indolone derivative.

Levodopa with carbidopa (Sinemet, Parcopa)


Levodopa with carbidopa can improve sensory symptoms and periodic leg movements of sleep (PLMS) in primary RLS and in secondary RLS due to uremia. Most patients experience benefits with doses of 25/100 mg (in mild cases), with a maximum dosage of 50/200 mg/day.

Dosages higher than 50/200 mg/day are accompanied by marked augmentation of symptoms in 85% of patients. Adjunctive therapy with reduction of levodopa dose or discontinuance of levodopa and substitution with a dopamine agonist drug may help. Sinemet is preferred for patients with occasional and mild symptoms.

Bromocriptine mesylate (Parlodel, Cycloset)


Bromocriptine mesylate is a dopamine D2-receptor agonist that has been found to be effective in RLS. However, it is usually poorly tolerated because of nausea and orthostatic hypotension. Other dopamine agonists, such pramipexole, are preferred.

Rotigotine (Neupro)


Rotigotine is a dopamine agonist stimulating D3, D2, and D1 receptors. It is indicated for treatment of moderate-to-severe primary RLS. It is available as a transdermal patch that provides continuous delivery for 24 hours.


Anxiolytics, Benzodiazepines

Class Summary

A benzodiazepine may be used as monotherapy in patients with mild or intermittent symptoms of RLS or as a component of combination therapy in severe cases. Clonazepam has been shown to ease sensory symptoms and PLMS in RLS. Other benzodiazepines, such as temazepam and alprazolam, also can be effective.

Clonazepam (Klonopin)


No controlled trials have demonstrated that clonazepam or any other gamma-aminobutyric acid (GABA)-ergic sedative hypnotic actually reduces the symptoms of RLS. Clonazepam's therapeutic benefit appears to arise from sleep-promoting properties that allow the patient to continue to sleep despite disturbances from RLS symptoms.


Opioid Analgesics

Class Summary

Low-potency opioids (eg, codeine) can benefit patients with mild and intermittent symptoms; higher-potency agents (eg, oxycodone hydrochloride, methadone hydrochloride, and levorphanol tartrate), may have a role in refractory cases. Because of the risk of addiction, these drugs should be used with caution; their use usually is recommended only in refractory cases, especially in ones with a prominent pain component.



Codeine and other opioids can be helpful in decreasing the symptoms of RLS, serving as a treatment of second choice when other treatments have failed or have caused augmentation problems.


Anticonvulsants, Other

Class Summary

Anticonvulsants are being used more frequently for the treatment of moderate-to-severe RLS. They are particularly helpful in patients with a strong neuropathic symptom component or with comorbid neuropathy.

Gabapentin Enacarbil (Horizant)


A prodrug of gabapentin, gabapentin enacarbil, has been approved by the FDA. In a randomized, placebo-controlled study, 600 mg orally, taken once daily at 5 PM, provided sustained gabapentin exposure and maintained improvements in RLS symptoms in comparison with placebo.[29]

Gabapentin (Neurontin)


Gabapentin is indicated for patients whose symptoms include pain, neuropathy, or both. It may be used as a single treatment or with other treatments.

Pregabalin (Lyrica)


Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit). Its mechanism of action is unknown. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. This agent is FDA-approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures. It is not FDA-approved for the treatment of RLS.


Alpha2-Adrenergic Agonists

Class Summary

Presynaptic alpha2 -adrenergic agents stimulate alpha2 adrenoreceptors in the brainstem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow.

Clonidine hydrochloride (Catapres, Kapvay, Nexiclon XR)


Clonidine hydrochloride may be effective in primary RLS, as well as in RLS associated with uremia. However, it has no effect on PLMS.


Iron Salt

Class Summary

Iron salt is used to correct iron deficiency resulting from chronic hemodialysis.

Iron sucrose (Venofer)


Iron sucrose is used to treat iron deficiency (in conjunction with erythropoietin) due to chronic hemodialysis. Iron sucrose has shown a lower incidence of anaphylaxis than other parenteral iron products. Parenteral iron sucrose has also been shown to improve symptoms of RLS in patients with RLS and low ferritin levels. Parenteral iron sucrose is not FDA-approved for the treatment of RLS.

Contributor Information and Disclosures

Ali M Bozorg, MD Assistant Professor, Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine

Ali M Bozorg, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Academy of Sleep Medicine

Disclosure: Received honoraria from Cyberonics for speaking and teaching; Received honoraria from UCB, Inc. for speaking and teaching.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.


Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the Medscape Reference articles that I wrote or edited.

William G Irr, MD Consulting Staff, Department of Neurology Service, St Luke's Episcopal Hospital of Houston

William G Irr, MD is a member of the following medical societies: American Academy of Neurology.

Disclosure: Nothing to disclose.

Juan Latorre, MD Research Fellow, Department of Physical Medicine and Spinal Cord Injury Medicine, The Institute for Rehabilitation and Research

Juan Latorre, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center, Florida Center for Neurology

Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, and American Society of Neuroimaging

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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