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 < 0.001) and was associated with a higher PGI response (68.1% vs 15.1%; p < 0.001) and improvements in periodic limb movements (PLM) index, PGI improvement scale, Clinical Global Impression improvement, and IRLS (all p < 0.001), patient-reported SE (p = 0.019), and quality of sleep (p < 0.001). After 12 months (phase 2), double-blind pergolide maintained improvements in PLMS arousal index and PLM index. Placebo patients switched to open-label pergolide in phase 2 exhibited marked improvements in these measures that were maintained at 12 months. Pooled results from the blinded and open-label pergolide groups demonstrated improvements at 12 months in the PLMS arousal index (p = 0.028) and PLM index (p < 0.0001) compared with placebo. Nausea and headache were more frequent with pergolide than with placebo treatment.
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.