What are the symptoms of Restless Legs Syndrome (RLS)?

From the Guidelines

Restless Legs Syndrome (RLS) symptoms should be managed with a combination of lifestyle modifications and medications, prioritizing dopamine agonists and alpha-2-delta calcium channel ligands as first-line treatments, as recommended by the American Academy of Sleep Medicine clinical practice guideline 1. The symptoms of RLS include an uncomfortable urge to move the legs, typically occurring during periods of rest or inactivity, especially in the evening or at night. These sensations are often described as crawling, creeping, pulling, throbbing, aching, or itching, and are temporarily relieved by movement. Some key points to consider in managing RLS symptoms include:

• Lifestyle modifications, such as regular exercise, maintaining good sleep hygiene, avoiding caffeine and alcohol, and practicing relaxation techniques, can help alleviate mild RLS symptoms.
• For moderate to severe symptoms, medications such as dopamine agonists (e.g., pramipexole or ropinirole) or alpha-2-delta calcium channel ligands (e.g., gabapentin or pregabalin) are effective treatments, as stated in the clinical practice guideline 1.
• Iron supplementation is also recommended if ferritin levels are below 75 ng/mL, as iron deficiency may contribute to RLS symptoms.
• Regular follow-up is crucial to monitor symptom control and medication side effects, ensuring the best possible outcome for patients with RLS.

From the FDA Drug Label

The effectiveness of ropinirole in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled trials in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria Patients were required to have a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. A variety of measures were used to assess the effects of treatment, including the IRLS scale and Clinical Global Impression-Global Improvement (CGI-I) scores The IRLS scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood associated with RLS. In all 3 trials, a statistically significant difference between the treatment group receiving ropinirole and the treatment group receiving placebo was observed at Week 12 for both the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders (much improved or very much improved) on the CGI-I

Ropinirole is effective in treating RLS symptoms, as demonstrated by a statistically significant difference in the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders on the CGI-I compared to placebo 2.

• The mean change in total IRLS scale score at Week 12 was -13.5, -11, and -11.2 for ropinirole in RLS-1, RLS-2, and RLS-3 trials, respectively, compared to -9.8, -8, and -8.7 for placebo.
• The percentage of responders on CGI-I at Week 12 was 73.3%, 53.4%, and 59.5% for ropinirole in RLS-1, RLS-2, and RLS-3 trials, respectively, compared to 56.5%, 40.9%, and 39.6% for placebo.

From the Research

RLS Symptoms

• Restless legs syndrome (RLS) is characterized by paresthesia and an urge to move, with symptoms occurring at rest in the evening or at night, and alleviated by moving the affected extremity 3, 4, 5, 6
• Symptoms begin or worsen during periods of rest or inactivity and are worse in the evening or at night 4, 6
• RLS is accompanied or caused by uncomfortable sensations in the legs, such as dysesthesia 5
• Other features supportive of a diagnosis include a family history, the presence of periodic leg movements in sleep, and the relief of symptoms after treatment with a dopaminergic therapy 6

Prevalence and Impact

• RLS prevalence in the general population has been estimated to be approximately 5% 3
• RLS can severely affect quality of life and disturb sleep, especially for elderly patients 7
• RLS significantly impacts patients' quality of life and remains a therapeutic area sorely in need of innovation and a further pipeline of new, biologically informed therapies 4

Diagnosis and Treatment

• Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms 4
• First-line management options include iron-replacement therapy, gabapentin, pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine 4, 7
• Second-line therapies include intravenous iron infusion and opioids including tramadol, oxycodone, and methadone 4, 7