MINNEAPOLIS — Two dopamine agonists—pramipexole and ropinirole—each improved symptoms and quality of life in adults with restless legs syndrome, based on data from studies presented at the annual meeting of the Associated Professional Sleep Societies. Both drugs are approved by the Food and Drug Administration for the treatment of restless legs syndrome.
Patients with restless legs syndrome (RLS) often report uncomfortable sensations deep in their legs accompanied by irresistible urges to move their legs. The symptoms worsen at night and tend to disrupt sleep, which has a negative impact on patients' quality of life.
Data from three randomized, double-blind, placebo-controlled studies of pramipexole showed that those who received the drug reported significant improvements in quality of life and in RLS symptoms, compared with placebo patients. The dosage used in the three studies ranged from 0.125 mg/day to 0.75 mg/day. The studies included a total of 784 adults (aged 18–79 years; average age 51 years); all patients met the diagnosis for RLS and had at least one postbaseline evaluation. All three studies were supported by Boehringer Ingelheim Pharmaceuticals Inc.
In the largest of the three studies, the 258 patients randomized to receive pramipexole for 12 weeks reported significant improvements in sleep quality, shorter time to fall asleep, and improved daytime symptoms, compared with 86 patients who received a placebo. Based on visual analog scale scores, daytime symptom severity improved by 49% in the pramipexole group, compared with 32% in the placebo group, and pramipexole patients reported an average of 57% improvement in sleep satisfaction, vs. 38% in the placebo group. The study was conducted by Dr. Robert D. Ballard of the University of Colorado Health Sciences Center in Denver.
Pramipexole did not increase daytime sleepiness, compared with placebo, across these three studies. In fact, the pramipexole patients who reported abnormal daytime sleepiness at baseline reported significant improvement in daytime sleepiness, compared with placebo patients, based on the Epworth Sleepiness Scale. No significant differences appeared in daytime sleepiness among patients in the two groups that reported normal levels of daytime sleepiness at baseline.
In a pair of similar studies of ropinirole, presented by Dr. Markus H. Schmidt of the Ohio Sleep Medicine Institute in Dublin, Ohio, the drug significantly improved the symptoms of restless legs syndrome and improved patients' quality of life in a randomized trial with an intent-to-treat population of 382 adults with RLS. The daily dose ranged from 0.5 to 6.0 mg, titrated as needed. Dr. Schmidt has received financial support from and has served as a speaker for GlaxoSmithKline, the company that supported the research.
After 12 weeks, the 187 patients who received ropinirole reported significantly greater improvements in symptoms, compared with the 195 placebo patients, in four areas of the Medical Outcomes Study Sleep Scale (reduction in sleep disturbance, reduction in daytime sleepiness, increased sleep adequacy, and increased sleep quantity). Adverse events were mild to moderate, and only 4% of the ropinirole patients and 3% of the placebo patients discontinued the medications because of adverse events. The most often reported adverse events in the ropinirole group vs. the placebo group were nausea (28% vs. 7%), headache (20% vs. 18%), and sleepiness (9% vs. 6%).
After treatment, nearly half (49%) of the ropinirole patients were classified as “not ill” or “borderline ill,” compared with 31% of placebo patients, based on a clinician-rated scale. In addition, significantly more patients showed improvement in illness based on a patient-rated scale at 2 days, 3 days, and 4 days after starting treatment. On day 4, 42% of the ropinirole patients were classified as responders, compared with 24% of the placebo patients.