Effectiveness and Tolerability of Istradefylline for the Treatment of Restless Legs Syndrome: An Exploratory Study in Five Female Patients

Background: Studies of istradefylline (KW6002), an adenosine A_2A-receptor antagonist, have provided evidence of its efficacy as a nondopaminergic antiparkinsonian drug. Antiparkinsonian drugs have also had efficacy in treating restless legs syndrome (RLS).Objectives: The aims of this study were to assess the effectiveness and tolerability of istradefylline in the treatment of RLS.Methods: This was a single-center, multiparametric, prospective trial of istradefylline as a treatment for moderate to severe idiopathic RLS. It was conducted at the Shands/Jacksonville Sleep Disorders Center, University of Florida, Jacksonville, Florida, from March 2003 to October 2003. Patients received a single PO 80-mg dose QD of istradefylline in the late afternoon or early evening for 6 weeks. Appropriate tolerability evaluations (ie, vital assessments, physical examination, clinical laboratory tests, and electrocardiogram) were performed at screening, while on study drug, and after withdrawal of study drug.Results: Fifteen participants (mean [SD] age, 61 [7.1] years; range, 50-69 years) were screened for enrollment. The mean duration of RLS was 18 years. Of the 15 potential patients, 6 did not meet entry criteria, 2 withdrew consent, 1 had not completed baseline procedures at the time of study suspension, and 1 was excluded for administrative reasons. Therefore, a total of 5 patients received the study drug. Of these, 3 (60%) patients responded favorably to istradefylline treatment. Improvement in the periodic limb movement index was observed in 3 patients compared with baseline (patients 2, 4, and 5 [index score: 6, 4, 9 vs 50, 35, 18, respectively]). Improvement in the International RLS Rating Scale scores was observed in 3 patients compared with baseline (patients 2, 4, and 5 [index score: 7, 23, 9 vs 35, 25, 20, respectively]). There was a return to baseline severity in 2 of the 3 patients after withdrawal of study drug. Improvement in RLS symptoms was observed in 3 patients treated with istradefylline for 6 weeks. A clinical worsening of baseline insomnia was observed in 2 patients.Conclusions: Although we could not definitively conclude a beneficial effect based on this small exploratory trial, we found the data to be encouraging. The study drug was well tolerated. Further study of this compound in the treatment of RLS is justified.