Efficacy of pergolide in treatment of restless legs syndrome: The PEARLS study

Objective: To evaluate the short- and long-term safety and efficacy of pergolide therapy for restless legs syndrome (RLS) in a double-blind, placebo-controlled, randomized trial (Pergolide European Australian RLS [PEARLS] study). Methods: We randomized 100 patients with idiopathic RLS were randomized to pergolide, 0.25 to 0.75 mg, in the evening or placebo for 6 weeks (phase 1); thereafter, patients with response on the Patient Global Impression (PGI) scale continued on double-blind pergolide or placebo, and nonresponders received open-label pergolide up to 1.5 mg/d for 12 months of treatment (phase 2). Sleep efficiency (SE) and periodic limb movements during sleep (PLMS) arousal index were monitored by centrally evaluated polysomnography (PSG). The severity of RLS was assessed using the validated International RLS Scale (IRLS). Results: In phase 1 (change from baseline to week 6), pergolide reduced PLMS arousal index vs placebo (mean ± SD, −12.6 ± 10.0 vs −3.6 ± 15.9; p = 0.004), and SE did not improve (mean ± SD, +11.3 ± 11.9% vs +6.1 ± 18.6%; p = 0.196). Pergolide improved RLS severity score (−12.2 ± 9.9 vs −1.8 ± 7.5 placebo; p p p p = 0.019), and quality of sleep ( p p = 0.028) and PLM index ( p Conclusions: Pergolide substantially improves periodic limb movement measures and subjective sleep disturbance associated with restless legs syndrome. Low-dose pergolide was well tolerated and maintained its efficacy in the long term.