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

Abstract

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 (Emax,IRLS) and CGI‐I response rate (Emax,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 Emax,IRLS of dopaminergic agonists. Typical Emax,IRLS of dopaminergic agonists was expressed as −7.7−0.682×( baseline IRLS score −24) points. Typical Emax,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.

Sleep related movement disorders in the elderly: a review of recent literature

“…• Review potential causative medications (dopamine blockers, SSRI, SNRI) As there are currently no specific guidelines for the management of RLS in the elderly, in utilizing the recommended medications for RLS, careful consideration of potential augmentation and possible side effects in this vulnerable population is important in choosing a management strategy (Table 2). Side effects may include sedation, dizziness, respiratory depression, impulse control disorders, other cognitive disturbances, depression, gait instability, or weight gain (Garcia-Borreguero et al, 2019;Zhang et al, 2019). Side effects may be more common in the older populations (By the 2019 American Geriatrics Society Beers Criteria R Update Expert Panel, 2019), and slow titration up to the lowest effective dose is recommended.…”