Clinical Question: Is ropinirole (Requip) effective in patients with restless legs syndrome?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: Dopamine agonists such as pergolide (Permax) and levodopa (Larodopa) seem to have a positive effect in patients with restless legs syndrome, although some of the effect may be a placebo response. The investigators conducting this study enrolled 381 patients (average age = 52 years). All patients had restless legs syndrome as defined by diagnostic criteria. The authors excluded patients who might have had secondary restless legs caused by renal failure, pregnancy, or iron deficiency. Patients were randomized (allocation concealment uncertain) to receive placebo or ropinirole 0.25 mg one to three hours before bedtime. The dosage could be titrated to a maximum of 4 mg per day, although the median dose at the end of the study was 2 mg (4 mg in the placebo group).

Patients were evaluated after three days and at one week, weekly for the next five weeks, and then every other week for a total of 12 weeks. At the start of the study, the mean score on the International Restless Legs Scale was 22 out of a possible 40. The score decreased in both groups, to an average of 11.9 in the placebo-treated group and to 8.4 in the ropinirole-treated group (P < .001). The clinical relevance of this drop, or of the difference between the groups, has not been determined with this scale.

Sleep disturbance, measured using the Medical Outcomes Study questionnaire, dropped from an average of 60 out of a possible 100 at baseline to 38.9 in the placebo group and 29.1 in the treatment group (P < .001). Sleep quantity and adequacy, daytime somnolence, and sleep problem index also were improved compared with placebo. Most patients (83 percent) in the ropinirole group reported at least one adverse event during the study, as did 67 percent of patients in the placebo group. These effects could be responsible for the large placebo response during the study.

Bottom Line: Ropinirole seems to have an effect on symptoms of restless legs, at least in the short term. The magnitude of the effect is not known because there was a profound placebo response in this study. The average dose in the study was titrated up to 2 mg; in the United States, all strengths are approximately the same price. Once the effective dose is found, using that specific tablet size should result in significant savings over the use of 0.25-mg tablets. (Level of Evidence: 1b–)