Effectiveness of Ropinirole and Gabapentin for the Treatment of Restless Legs Syndrom in Patients on Maintenance Hemodialysis: a Randomized, Blinded, Placebo-Controlled Trial

Purpose

Restless legs syndrome (RLS), also known as Willis-Eskbom disease, is a neurologic disorder characterized by 1) an urge to move the legs, 2) uncomfortable sensations in the legs, 3) symptoms that are often worse the evening or when at rest , and 4) may be temporarily relieved by physical activity. While the precise pathogenic mechanisms responsible for uremic RLS remain unknown, there is evidence to support involvement of dopaminergic dysfunction and reduced iron stores.

RLS is separated into primary/idiopathic and secondary forms. Secondary RLS is usually associated with underlying medical conditions such as end-stage kidney disease (ESKD). The overall prevalence of RLS in the general population is estimated to be around 10%. However, the prevalence of RLS in the ESKD population is significantly higher. A systematic review calculated weighted mean RLS prevalence of 30% (range: 8-52%) in ESKD. Studies have shown that RLS has a substantial negative impact on both the physical and the mental health dimensions of quality of life (QOL), such as depression, anxiety, pain, fatigue and sleep disorder.

While non-pharmacological measure should be considered for all patients, pharmacological treatment for RLS is indicated when the symptoms lead to significant insomnia or impaired quality of life. Although only two medications have been approved by Health Canada, there is a long list of medications that have been used in management of RLS symptoms. Gabapentin and dopamine agonists are usually the first choices in treating RSL. Although marketed in Canada, gabapentin and ropinirole have not been approved by Health Canada for the treatment of moderate-severe restless legs sydnrome.

Unfortunately, the prolonged treatment of RLS using dopaminergic drugs, such as the approved pramipexole, can lead to a phenomenon called augmentation in which patients experience an increase in symptom severity, an earlier onset of symptoms during the night, the appearance of daytime symptoms, and/or the spread of symptoms to other parts of the body. Although, ropinirole is a dopamine agonist it appears to have a lower risk of augmentation and tolerance than other dopaminergic drugs, such as levodopa.