Effect of pramipexole on RLS symptoms and sleep: A randomized, double-blind, placebo-controlled trial

Background: Patients with Restless Legs Syndrome (RLS) often seek treatment because of sleep problems related to nocturnal symptoms. Our goal was to test the ability of pramipexole to improve sleep in RLS patients and to reconfirm its efficacy for primary RLS symptoms. Methods: Adults with moderate or severe RLS were randomized to receive placebo or pramipexole (flexibly titrated from 0.25 to 0.75 mg), 2-3 h before bedtime for 12 weeks. The co-primary outcome measures were change in Medical Outcomes Study (MOS) sleep disturbance score and International RLS Study Group Rating Scale (IRLS) score at 12 weeks. Results: The intent-to-treat population included 357 patients: 178 received pramipexole and 179 received placebo. At 12 weeks, the adjusted mean change from baseline was greater for pramipexole (vs. placebo) for IRLS score (-13.4 ± 0.7 vs. -9.6 ± 0.7) and MOS sleep disturbance score (-25.3 ± 1.5 vs. -16.8 ± 1.5) (p ≤ 0.0001; ANCOVA). Responder rates (clinical and patient global impression and IRLS) were also significantly higher in the pramipexole group. RLS-QOL score was improved over placebo at Week 12 (p <0.01) as were MOS sleep adequacy (p = 0.0008) and quantity (p = 0.08) scores. Nine percent of patients in each group withdrew because of adverse events. Conclusions: Pramipexole is effective and well-tolerated for RLS and related sleep disturbance.