Managing Restless Leg Syndrome: Current Strategies and Treatment Guidelines

In this session, Stephany Fulda, PhD, described current issues that are being faced in clinical practice and the considerations that must be taken into account when treating restless leg syndrome (RLS). She discussed the importance of insomnia and periodic leg movement in relation to RLS.

Starting with a case report by Kurlan et al, Fulda discussed a 6-year patient case history of RLS that included a typical clinical progression. Through this report, Fulda was able to demonstrate that only a few patients are able to experience long-term relief with the use of a single drug. Commenting on the case report, Fulda stated that “We are looking only at symptomatic treatment.”

When formulating a treatment plan for RLS, a number of factors should be taken into consideration. For instance, drug-induced RLS may stem from the use of certain medications. Mirtazapine has an approximate 30% chance of inducing RLS symptoms; by comparison, paroxetine, sertraline, and other psychiatric medications only have an approximate 5% chance of causing RLS symptoms.

As there is a relationship between iron deficiency and RLS, iron supplementation may lead to clinical improvements of RLS symptoms. Iron deficiency is thought to contribute to the pathophysiology of RLS, and although many patients with RLS do not have iron deficiency, individuals with low ferritin may benefit from the correction of low ferritin levels. By correcting the underlying cause of low ferritin levels, which may be consequent to comorbid conditions, a patient’s symptoms of RLS may be improved.

In addition to iron deficiency and certain medications, sleep deprivation, caffeine and/or alcohol intake, strenuous exercise, and even idiosyncratic patient factors may exacerbate symptoms of RLS. Asking patients to actively maintain a log of RLS symptoms that are experienced in association with the consumption of certain foods may help to control and reduce the severity of symptoms.

Also, it is possible for a patient to experience the onset of RLS symptoms during pregnancy; however, the symptoms may disappear after delivery.

Fulda recommended the use of diaries to record symptoms, severity rating scales, and quality-of- life measures to help clinicians establish a baseline for the extent and severity of RLS before instituting therapy. Fulda emphasized the utility of the Augmentation Severity Rating Scale in assessing RLS; the rating scale evaluates the timing of initial symptoms and the progression of symptoms over time.

Fulda emphasized the importance of interdisciplinary communication, and the case management of a patient with RLS should include identifying and communicating with caregivers, specialists, general practitioners, and the patient’s family. Fulda also noted that RLS may present as an emergency. Setting goals and realistic treatment expectations for patients also comprises an important component of therapy. Fewer than 25% of patients experience complete remission of RLS symptoms with treatment, and while response rates for treatment range from 50% to 80%, rates of withdrawal from treatment in long-term observational studies are also high, between 13% and 51%.

RLS severity correlates with insomnia, which often worsens mood disorders. Periodic leg movements are often reduced by the use of pramipexole; however, EEG disturbances may continue to occur. By contrast, clonazepam reduces the incidence of EEG disturbances, but has no effect on leg movements. Fulda used these findings to illustrate that the cause of RLS has not been fully elucidated. After all, if the EEG disturbance causes RLS, why did the treatment of EEG disturbances with clonazepam have no effect on leg movement? Unfortunately, the answer remains elusive.

Pharmacologically, the number of therapeutic options has increased over the last 2 years. Rotigotine, which has a very long half-life, has been on the market in Europe for some time but was only recently approved and marketed in the United States.

US treatment guidelines published in 2012 recommend pramipexole and ropinirole as the standards of care, with levodopa, opioids, and gabapentin as guideline-recommended alternative treatments. The use of all agents, except for opioids, was supported by high levels of clinical evidence. The use of opioids is only supported by a moderate level of clinical evidence. Fulda speculated that rotigotine may be implemented into the US treatment guidelines for RLS, perhaps as a standard of care, as it has been in European guidelines.