The dopamine receptor agonist rotigotine significantly reduced symptoms of restless legs syndrome in a multicenter placebo-controlled trial.
Administered via transdermal patch, rotigotine improved scores on both the International Restless Legs Syndrome Study Group rating scale (IRLS) total score and the Pittsburgh Sleep Quality Index (PSQI), Dr. Yuichi Inoue and his colleagues wrote in Sleep Medicine (2013 Aug. 21 [doi: 10.1016/j.sleep.2013.07.007]).
An interaction analysis suggested that baseline symptoms significantly correlated with treatment results, according to Dr. Inoue of Tokyo Medical University and his coauthors.
Rotigotine is a non-ergotamine dopaminergic agonist that was approved in the United States in 2007 for Parkinson’s disease. A year later, it was pulled from the market because the drug tended to crystallize within the patch, leading to underdosing. It was reapproved last year for moderate to severe restless legs syndrome.
The study was conducted at 44 institutions in Japan from February to December 2010. It randomized 284 adults with restless legs syndrome either to the rotigotine patch in a dosage of 2 mg or 3 mg or to placebo patch. The patients’ mean age was 51 years. About 60% of each group had severe restless legs syndrome as characterized by their IRLS score. The mean PSQI score was 7.6, indicating poor sleep quality.
A 5-week titration period was followed by 8 weeks of steady-state treatment. Down-titration was permitted if adverse events occurred; 5 patients were down-titrated. Treatment was discontinued in 31 patients; the most common reason was an adverse event, usually a skin reaction.
Patients in the active groups showed improvements in both outcome measures as early as 1 week after treatment began, the investigators reported. By the end of the study, the mean IRLS score decreased by 14.3 points in the 2-mg group, 14.6 points in the 3-mg group, and 11.6 points in the placebo group – a significant difference. Sixty percent of those taking 2 mg were considered responders, as were 66% of those taking 3 mg and 47% of those taking placebo.
The mean changes in the total PSQI were not significantly different between the active and placebo groups. However, the authors said, at the end of the study, the proportion of patients with a score of less than 5.5 (a total score of 5.5 or higher was defined as pathologic sleep disturbance) was significantly greater in the 2- and 3-mg groups than in the placebo group (77% and 74% vs. 56%, respectively).
The investigators also found some significant associations when they performed an interaction analysis. "The improvements ... among patients with more severe insomnia were greater in both rotigotine groups than in the placebo group when the patients were stratified by the PSQI total score. Patients with more severe insomnia also showed a greater improvement in insomnia symptoms following treatment with rotigotine."
Most patients taking the study drug experienced some form of adverse event (80% at 2 mg, 86% at 3 mg) – significantly more than those taking placebo (52%). Most of the problems were application-site reactions. Other adverse events that were more common in the active groups included nausea and somnolence.
The study was supported by Otsuka Pharmaceutical.