PURPOSE: Restless legs syndrome (RLS) is characterized by an irresistible urge to move the legs during rest or sleep, often accompanied by unpleasant leg sensations. The nonergot dopamine agonist pramipexole has been found effective, but there remains the practical issue of optimizing a patient's regimen to identify the lowest effective dose.
METHODS: We analyzed data from three double-blind, placebo-controlled trials of pramipexole at doses of 0.125 to 0.75 mg/d. All trials were double-blind and placebo-controlled, and patients met all RLS diagnostic criteria of the International RLS Study Group, including a baseline score >15 on the Group's RLS severity scale (IRLS). The RLS-specific IRLS and the generic Patient Global Impression scale (PGI) enabled patients to rate their changing clinical status.
RESULTS: The six-week flexible-dose trial had 224 pramipexole and 114 placebo recipients. After a week at 0.125 mg/d, 30.6% of the pramipexole group rated themselves as “much” or “very much” better on the PGI (“PGI responders”), compared with 7.0% for placebo (p<0.0001). Among IRLS responders (patients who had at least a 50% reduction in IRLS total score) on pramipexole, 19.7% had required only 0.125 mg/d, and 88.1% had required not more than 0.50 mg/d. The 12-week fixed-dose trial had 254 pramipexole and 85 placebo recipients. After a week at 0.125 mg/d, 42.5% of the pramipexole group were PGI responders, compared with 14.1% for placebo (p<0.0001). The three-week fixed-dose trial had 86 pramipexole and 21 placebo recipients. The adjusted mean IRLS decrease exceeded that of placebo by 6.2 for 0.125 mg/d (p=0.0055), 9.2 for 0.25 mg/d (p<0.0001), 11.2 for 0.50 mg/d (p<0.0001), and 9.9 for 0.75 mg/d (p<0.0001).
CONCLUSION: At flexibly titrated doses (simulating real-world practice), a week of pramipexole at 0.125 mg/d was often effective against RLS, and higher doses often converted nonresponders into responders. At fixed doses, regimens ranging from 0.125 to 0.75 mg/d were all found to be effective.
CLINICAL IMPLICATIONS: Low-dose pramipexole is often effective in RLS.
DISCLOSURE: Eric Lainey, No Product/Research Disclosure Information; Grant monies (from industry related sources) This study was supported by Boehringer Ingelheim International GmbH; Employee Eric Lainey, MD; Stefan Albrecht, MD; and Juergen Koester, PhD are employees of Boehringer Ingelheim.