BACKGROUND: Dopaminergic medications relieve symptoms of the restless legs 
syndrome (RLS) but have the potential to cause iatrogenic worsening 
(augmentation) of RLS with long-term treatment. Pregabalin may be an effective 
alternative.
METHODS: In this 52-week, randomized, double-blind trial, we assessed efficacy 
and augmentation in patients with RLS who were treated with pregabalin as 
compared with placebo and pramipexole. Patients were randomly assigned to 
receive 52 weeks of treatment with pregabalin at a dose of 300 mg per day or 
pramipexole at a dose of 0.25 mg or 0.5 mg per day or 12 weeks of placebo 
followed by 40 weeks of randomly assigned active treatment. The primary analyses 
involved a comparison of pregabalin and placebo over a period of 12 weeks with 
use of the International RLS (IRLS) Study Group Rating Scale (on which the score 
ranges from 0 to 40, with a higher score indicating more severe symptoms), the 
Clinical Global Impression of Improvement scale (which was used to assess the 
proportion of patients with symptoms that were "very much improved" or "much 
improved"), and a comparison of rates of augmentation with pregabalin and 
pramipexole over a period of 40 or 52 weeks of treatment.
RESULTS: A total of 719 participants received daily treatment, 182 with 300 mg 
of pregabalin, 178 with 0.25 mg of pramipexole, 180 with 0.5 mg of pramipexole, 
and 179 with placebo. Over a period of 12 weeks, the improvement (reduction) in 
mean scores on the IRLS scale was greater, by 4.5 points, among participants 
receiving pregabalin than among those receiving placebo (P<0.001), and the 
proportion of patients with symptoms that were very much improved or much 
improved was also greater with pregabalin than with placebo (71.4% vs. 46.8%, 
P<0.001). The rate of augmentation over a period of 40 or 52 weeks was 
significantly lower with pregabalin than with pramipexole at a dose of 0.5 mg 
(2.1% vs. 7.7%, P=0.001) but not at a dose of 0.25 mg (2.1% vs. 5.3%, P=0.08). 
There were six cases of suicidal ideation in the group receiving pregabalin, 
three in the group receiving 0.25 mg of pramipexole, and two in the group 
receiving 0.5 mg of pramipexole.
CONCLUSIONS: Pregabalin provided significantly improved treatment outcomes as 
compared with placebo, and augmentation rates were significantly lower with 
pregabalin than with 0.5 mg of pramipexole. (Funded by Pfizer; 
ClinicalTrials.gov number, NCT00806026.).