Quantitative Comparison of the Efficacies of 5 First-Line Drugs for Primary Restless Leg Syndrome

Comparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restless leg syndrome (RLS) are lacking because of the few head-to-head clinical trials. A model-based meta-analysis approach was employed to quantitatively compare the efficacies of these 5 first-line RLS drugs. Longitudinal efficacy data of RLS drugs were collected from published eligible literature. Mean changes in both the International Restless Leg Syndrome Study Group (IRLS) rating scale and Clinical Global Impression Improvement (CGI-I) scale response rate were analyzed. A study-level population pharmacodynamic model was used to fit the dose-effect relationship and to describe the therapeutic effect over time for RLS drugs and placebo, and the typical efficacies of these drugs were compared. The onset of action was rapid for RLS drugs. In the placebo group, typical maximum IRLS reduction (E_max,IRLS ) and CGI-I response rate (E_max,CGI-I ) were -9.34 points and 48.2%, respectively. After deducting placebo effects, we found that the baseline IRLS score was significantly correlated with the E_max,IRLS of dopaminergic agonists. Typical E_max,IRLS of dopaminergic agonists was expressed as $$ points. Typical E_max,IRLS values of pregabalin and gabapentin enacarbil were -5.95 points and -4.00 points, respectively. The therapeutic effect of dopaminergic agonists was found to be associated with baseline symptom severity. In RLS patients with more severe symptoms, the therapeutic effect of dopaminergic agonists tended to be better than that of α-2-δ ligands.