Rest for Weary Legs

Restless leg syndrome may be treated with some medications

/ Author:  / Reviewed by: Robert Carlson, M.D

(RxWiki News) Restless legs syndrome is a disorder of the nervous system that causes uncomfortable urges to move limbs. Patients often wonder if there are medications that work, and if they are safe.

Restless legs syndrome causes sensations described as throbbing, pulling or creeping that leads to an uncontrollable urge to move the affected limbs. Patients typically experience these symptoms at night while resting or relaxing.

A review of previous studies on medications for restless legs syndrome found that several medications may help relieve the sensations of restless legs syndrome. These medications included rotigotine (Neupro) and levodopa-containing medications (Sinemet, Parcopa, Atamet, Stalevo, Madopar, and Prolopa).

The researchers said that deciding which treatment to try first should depend on each patient's situation, such as how severe the case is and the patient's other health conditions. Most patients did well with dopamine receptor agonists and calcium channel alpha-2 delta ligands, according to this review.

"Talk to your doctor about controlling your restless legs syndrome."

Diego Garcia-Borreguero, MD, PhD, from the Sleep Research Institute in Madrid, Spain and President of the International Restless Legs Syndrome Study Group (IRLSSG), led this study to find the best scientific recommendations for moderate to severe restless legs syndrome, also called Willis-Ekbom disease.

Dr. Garcia-Borreguero told dailyRx News that he and his team wanted to answer "...two important questions patients of [restless legs syndrome] have been asking for years: 'What is the efficacy of my treatment?' and 'What is the safety of this treatment?'"

The researchers were a Task Force formed by the International Restless Legs Syndrome Study Group (IRLSSG). The Task Force looked at studies on restless legs syndrome medications done in the previous two years.

To be included in this research, the studies must have lasted at least six months. The reviewed studies had either been presented at a professional meeting, posted on a pharmaceutical website or were published in a scientific journal.

The authors of this review looked at 61 studies on the effectiveness and safety of medications for moderate to severe restless legs syndrome. The Task Force made recommendations based on consensus, which they defined as at least 80 percent of the researchers agreeing on the research conclusion.

The researchers concluded that the medications pregabalin (Lyrica), gabapentin (Neurontin), gabapentin enacarbil (Horizant), pramipexole (Mirapex, Mirapexin, Sifrol) and ropinirole (Requip, Ronirol, Adartrel) relieved symptoms of restless legs syndrome for one year. Levodopa (Sinemet, Parcopa, Atamet, Stalevo, Madopar, and Prolopa) was determined to help for two years, and rotigotine (Neupro) is most likely effective for up to five years in around half of patients who did not have side effects or loss of effectiveness.

Prices of medications for restless legs syndrome vary greatly, from $0.18 per dose for Neurontin to $5-6 per dose for Horizant and $6-9 per dose for Neupro.

Only three medicines, Horizant, Requip and Mirapex, have been approved by the Food and Drug Administration (FDA) for treating restless legs syndrome. Other medications have been used successfully to treat the symptoms "off label."

The FDA regulations allow physicians to prescribe medications for conditions different than the intended conditions. This practice is known as "off label" use.

The authors found safety concerns with the medications pergolide (Permax) and cabergoline (Cabaser, Dostinex). Pergolide and carbergoline were associated with fibrosis, a disease that causes scarring in the lungs and valvulopathy, a disorder of the heart valves. They recommend against using these medications.

The researchers noted that when doctors are prescribing, the medication chosen should depend on how severe the patient's condition is. They also stated that doctors should consider what other diseases a patient has when prescribing a medication.

The authors further determined that the best medications for most patients to try first are dopamine-receptor agonists and calcium-channel alpha-2 delta ligands.

Dopamine-receptor agonists,  such as Requip and Mirapex, are medications which activate dopamine receptors similar to dopamine, to allow communication between nerve cells. Dopamine-receptor agonists  were first used to treat Parkinson's disease.

Calcium-channel alpha-2 delta ligands are medications such as Lyrica and Neurontin which work similarly to the neurotransmitter gamma-aminobutyric acid (GABA) to bind to calcium channels, reducing influx of calcium into neurons. This may decrease the release of glutamate, norepinephrine and substance P, relieving neuropathic pain. Alpha-2 delta legands were first used for epilepsy. Their use for restless legs syndrome is currently "off label," except for Horizant.

"Our report provides the first comprehensive review of long-term treatment options for [restless legs syndrome] patients. We conclude that, in order to avoid complications of long-term use, either dopamine receptor agonists or alpha-2 delta ligands, depending on the clinical circumstances, are the best choice to initiate treatment," said Dr. Garcia-Borreago.

The research was limited by the length of the studies available. The authors stated that longer clinical studies are needed to help find the best long-term treatments for patients with restless legs syndrome.

"Ekbom disease has a significant worldwide prevalence with significant potential morbidity," William Kohler, MD, of the Florida Sleep Institute, told dailyRx News. "This article is important as it gives guidelines for practitioners as to the most efficacious medications to utilize for this condition."

This study was published in the July issue of Sleep Medicine.

The study was funded by the International Restless Legs Syndrome Study Group. Five of the authors have received grants from pharmaceutical companies and six of the authors are consultants for pharmaceutical companies. Additionally, two of the authors are on the scientific advisory board for pharmaceutical companies. Four of the authors reported no conflict of interest.

Reviewed by: 
Review Date: 
July 19, 2013
Last Updated:
January 2, 2014