Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome

Quilici, S.; Abrams, K.R.; Nicolas, A.; Martin, M.; Petit, C.; LLeu, P.-L.; Finnern, H.W.

doi:10.1016/j.sleep.2007.11.020

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Volume 9, Issue 7 , Pages 715-726, October 2008

Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome

S. Quilici
- i3 Innovus, 3rd floor, Beaufort House Cricket Field Road, Uxbridge UB8 1QG, United Kingdom
- Corresponding author. Tel.: +44 (0) 1895 455380x386; fax: +44 (0) 1895 520039.
- The author has no conflict of interest related to this article.
K.R. Abrams
- Department of Health Sciences, University of Leicester, 2nd Floor, Adrian Building, University Road, Leicester LE1 7RH, United Kingdom
- Professor Keith Abrams has received honoraria as a paid consultant to i3 Innovus.
A. Nicolas
- Unité d’Exploration Hypnologique, Service Hospitalo-Universitaire de Psychiatrie, Hôpital du Vinatier, 95 Bd Pinel, 69677 Lyon Bron, France
- Dr. Nicolas has received grants totalling less than USD 10,000 per year.
M. Martin
- i3 Innovus, 3rd floor, Beaufort House Cricket Field Road, Uxbridge UB8 1QG, United Kingdom
- The author has no conflict of interest related to this article.
C. Petit
- Boehringer Ingelheim France, 12 rue André Huet – B.P. 292, 51060 Reims CEDEX, France
- The author has no conflict of interest related to this article.
P.-L. LLeu
- Boehringer Ingelheim France, 12 rue André Huet – B.P. 292, 51060 Reims CEDEX, France
- The author has no conflict of interest related to this article.
H.W. Finnern
- Boehringer Ingelheim GmbH, Binger Straße 173, 55216 Ingelheim, Germany
- The author has no conflict of interest related to this article.

Received 4 April 2007; received in revised form 17 September 2007; accepted 16 November 2007.

Abstract

Objective

In the absence of comparative trials a meta-analysis was performed to compare the efficacy and tolerability of the non-ergot derived dopamine agonists, pramipexole and ropinirole, in restless legs syndrome (RLS).

Methods

Frequentist fixed and random-effects models were pre-specified for the direct comparisons and a Bayesian approach for the indirect comparison. Efficacy outcomes included the mean change from baseline in the International RLS Study Group Rating Scale (IRLS) score and the percentage of responders on the clinical global impressions – improvement scale (CGI-I). Safety outcomes included the incidence of withdrawal and adverse events.

Results

The direct meta-analysis confirmed superior efficacy for both treatments versus placebo for the IRLS (pramipexole: −5.45; 95% CI: −7.70; −3.20; ropinirole: −3.16; 95% CI: −4.26; −2.05) and the CGI-I (pramipexole: OR=2.98; 95% CI: 2.08; 4.26; ropinirole: OR=1.99; 95% CI: 1.52; 2.60). Placebo comparisons showed a significantly higher incidence of nausea for pramipexole (p<0.01), whereas nausea, vomiting, dizziness, and somnolence were significantly higher for ropinirole (all p<0.01). The indirect comparison showed with a probability of ⩾95%, a superior reduction in the mean IRLS score (−2.33; 95% credibility interval [CrI]: −4.23; −0.41), higher CGI-I response rate (OR=1.50; 95% CrI: 0.97; 2.32) and significantly lower incidence of nausea, vomiting, and dizziness for pramipexole compared to ropinirole.

Conclusion

Differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed. These findings should be further confirmed in head-to-head clinical trials.

Keywords: Restless legs syndrome, Meta-analysis, Pramipexole, Non-ergot dopamine agonists, Efficacy, Safety