Efficacy and safety of pramipexole in idiopathic restless legs syndrome: A polysomnographic dose-finding study—The PRELUDE study☆

Received 22 November 2005; received in revised form 16 February 2006; accepted 6 March 2006.

Abstract

Background and purpose

To evaluate the effects of pramipexole (0.125–0.75mg/d) on polysomnographic (PSG) measures and patient and clinician ratings of restless legs syndrome (RLS).

Patients and methods

Patients (n=109) with moderate to severe RLS were randomized to placebo or fixed doses of pramipexole during a 3-week, double-blind, placebo-controlled, dose-finding study.

Results

In each pramipexole dose group, the periodic limb movements during time in bed index (PLMI) decreased significantly, compared with placebo (adjusted mean difference in log-transformed data: 0.125mg, −1.54; 0.25mg, −1.93; 0.50mg, −1.89; and 0.75mg, −1.52; P<0.0001). At all doses, International RLS Study Group Rating Scale (IRLS) scores were also significantly reduced, with the greatest adjusted mean reduction in the 0.50mg group (−17.01). At all but the lowest pramipexole dose, the percentage of responders (≥50% reduction of IRLS score) was substantially higher than for placebo (61.9–77.3, vs 33.3%). In the pramipexole groups, 50.0–77.3% of patients rated their condition as ‘much better’ or ‘very much better’, compared with 38.1% of patients in the placebo group (P=0.0139 for the 0.50mg dose). Clinical global impressions (CGI) scale ratings of ‘much improved’ or ‘very much improved’ were given to 61.9–86.4% of patients in the pramipexole groups, compared with 42.9% in the placebo group (P<0.05 for the 0.25, 0.50, and 0.75mg groups). Pramipexole was well tolerated and did not produce somnolence at any dose.

Conclusion

Pramipexole is effective and safe in the treatment of both objective and subjective facets of RLS.

Keywords: Restless legs syndrome, RLS, Periodic limb movements, Sleep, Polysomnography, Pramipexole, Placebo-controlled

a Skogby Sleep Clinic, Rinnekoti Research Centre, Kumputie 3, FI-02980 Espoo, Finland

b Neurotest Tampere Oy, Hatanpään Valtatie 1, FIN-33100 Tampere, Finland

c Department of Clinical Neurophysiology, University Hospital of Helsinki, P.O. Box 340, FI-00029 Helsinki, Finland

d Finnish Institute of Occupational Health, Brain at Work Research Center, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland

e Department of Neurology, University of Helsinki, FI-00014 Helsinki, Finland

f Medical Division, Boehringer Ingelheim Finland Ky, Tammasaarenkatu 5, FI-00180 Helsinki, Finland

g Medical Division, Boehringer Ingelheim International GmbH, Binger Str. 173, 55216 Ingelheim, Germany

h Department of Clinical Research CNS, Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorferstr.65, 88397 Biberach, Germany

Corresponding author. Address: Skogby Sleep Clinic, Rinnekoti Research Centre, Kumputie 3, FI-02980 Espoo, Finland. Tel.:+358 9 8551345; fax: +358 9 8551375.

☆ PRELUDE, Pramipexole for RLS: efficacy and tolerability of the usage of dopamine agonists.

1 Dr Partinen has received a grant from the Rinnekoti Research Foundation for his studies on restless legs syndrome (RLS), and he has received honoraria, totaling less than USD10,000per year, for his presentations in postgraduate symposia on RLS.

2 The author has no conflict of interest related to this article.

PII: S1389-9457(06)00100-6

doi:10.1016/j.sleep.2006.03.011

4 of 14