Randomized trial of pramipexole for patients with restless legs syndrome (RLS) and RLS-related impairment of mood

Objectives: Patients with restless legs syndrome (RLS) have an elevated prevalence of mood disorders compared with the general population. We investigated the change of RLS-related mood impairment during treatment of RLS with pramipexole, a dopamine D-3/D-2 agonist. Methods: Adults with moderate to very severe RLS were enrolled in a 12-week, double-blind, placebo-controlled Phase IV pramipexole trial. A moderate to very severe RLS-related mood disturbance at baseline (score >= 2 on Item 10 of the International RLS Study Group Rating Scale [IRLS]) was also required. Pramipexole (0.125 to 0.75 mg once daily) was flexibly titrated over the first 4 weeks. Results: The intent-to-treat population comprised 199 patients on placebo and 203 on pramipexole. At week 12, adjusted mean total-score changes on IRLS were -14.2 +/- 0.7 for pramipexole and -8.1 +/- 0.7 for placebo (p < 0.0001), and on the Beck Depression Inventory version II, -7.3 +/- 0.4 for pramipexole and -5.8 +/- 0.5 for placebo (p = 0.0199). For IRIS item 10, the 12-week responder rate (reduction to no or mild mood disturbance) was 75.9% for pramipexole and 57.3% for placebo (p < 0.0001). Study withdrawal rates were higher for placebo (20.5%) than for pramipexole (12.8%). Conclusions: In patients with RLS-related mood disturbance, pramipexole improved RLS while also improving RLS-related mood impairment. Tolerability of pramipexole was similar to that in previous studies. (C) 2010 Elsevier B.V. All rights reserved.