LAUSR

Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum. Dipyridamole is a non-selective inhibitor of ENT1/ENT2 (the main reuptake mechanism of adenosine) and increases thereby extracellular adenosine. We hypothesized that treatment with dipyridamole would improve RLS symptoms more than placebo. We performed a randomized, double-blind, placebo-controlled clinical trial on 15 previously untreated idiopathic RLS patients that underwent a two week treatment with either 300 mg dipyridamol or placebo (randomized for the order of treatments), following a cross-over design. Treatment started with a dose of 100 mg/day, followed by a forced up-titration to 200 mg on day 4, and to 300 mg on day 7. Severity was assessed at baseline, day 7 and day 14 of each treatment condition by means of the IRLS and CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score). Fifteen patients (nine women), never before treated with dopaminergic agents, completed both arms of the study. Mean age was 60,2 (±7,1), and the mean duration of illness was 6,03 (±3,1) yrs. IRLS score improved during treatment with dipyridamole from a mean (±S.D.) of 24,36 (±3,3) to 9,78 (±3,4), in contrast to a change from 23,9 (±3,8) to 16,6 (±3,7) under placebo (p< 0.05). Corresponding improvements on the CGI were 61,3% and 11,8% for dipyridamole and placebo, respectively. 7/ 15 patients improved by more than 50% during treatment with dipyridamole vs. 4/15 under placebo. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing. These preliminary results suggest that dipyridamole is an effective agent on RLS symptoms. It also provides evidence of hypoadenosinergic mechanisms playing a central role in RLS. No funding was provided for this investigation.