In the first long-term active-comparator trial of efficacy and augmentation in restless leg syndrome (RLS), outcomes with pregabalin were better than those observed with pramipexole.
New Orleans, LA—In the first long-term active-comparator trial of efficacy and augmentation in restless leg syndrome (RLS), outcomes with pregabalin were better than those observed with pramipexole, reported Diego Garcia-Borreguero, MD, PhD, director of the Sleep Research Institute in Madrid, Spain, at the American Academy of Neurology 64th Annual Meeting.
Pramipexole is a dopamine agonist while pregabalin is an alpha-2-delta ligand.
Explaining the rationale for the comparative study, Dr Garcia-Borreguero noted that dopamine agonists are currently the first-line treatment for RLS, however, their long-term use is limited by augmentation and they only partly improve sleep.
“RLS requires, in most cases, chronic therapy. Patients will be on these drugs for most of their lives. The main problem is augmentation, an increase in the severity of symptoms as patients become tolerant. It makes sense to compare the efficacy and toxicity of these treatments,” said Dr Garcia-Borreguero.
He suggested that pregabalin has shown efficacy in improving RLS symptoms and sleep. With its non-dopaminergic mechanism of action, it may induce less augmentation.
The study assessed the relative efficacy of pregabalin, pramipexole, and placebo, and their ability to induce augmentation, in a 12-week placebo-controlled, 52-week active-comparator, randomized double-blind multicenter trial.
Investigators enrolled 719 participants with moderate-to-severe RLS, who received pregabalin 300 mg daily, pramipexole 0.25 mg daily, or pramipexole 0.5 mg daily for 52 weeks, or placebo for the first 12 weeks followed by randomization to one of the 3 active treatment arms for 40 additional weeks.
Improvement from the baseline of the study in RLS symptoms over placebo, as measured by the International RLS Study Group Rating Scale score, was greatest with pregabalin: -4.5 points (P <0.0001), compared with -0.6 with pramipexole 0.25 mg per day (NS) and -3.2 with pramipexole 0.5 mg per day (P <0.0001).
“The rate of augmentation over the long term was higher with either dose of pramipexole,” reported Dr Garcia-Borreguero.
In addition, on the Clinical Global Impressions (CGI) scale, the proportion of patients reporting “very much improved” or “much improved” symptoms was highest with pramipexole: 71.4% (P <0.0001), compared with 51.3% (NS) and 62.7% (P = 0.0022), respectively. On placebo, 46.8% of patients reported this level of improvement.
The study was sponsored by Pfizer, Inc.