![]() GEn is approved by the FDA at a dose of 600 mg once daily for the treatment of moderate-to-severe primary RLS in adults. Gabapentin enacarbil (GEn), an agent in the alpha-2-delta ligand class of drugs, is an actively transported prodrug of gabapentin. These developments may warrant switching to an alternate class of drugs when these side effects develop. Some RLS patients who are treated with DAs may also develop impulse control disorders. In particular, augmentation leads to a paradoxical scenario involving a worsening and earlier phase shift of RLS symptoms during treatment. Though initially effective, the benefit of treatment with DAs may lessen over time owing to a variety of factors which may include augmentation, tolerance, or dopaminergic down-regulation. Three DAs-ropinirole, pramipexole, and rotigotine-have been approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe primary RLS. ![]() Over the past decade, dopamine agonists (DAs) have been used as first-line therapy for patients with moderate-to-severe primary RLS. Patients with RLS experience significant impairments in sleep, daytime or social functioning, and overall quality of life. This urge is frequently accompanied by unpleasant sensations in the legs, worsens in the evening and at rest, and is transiently improved with activity. Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common neurological disorder characterized by an urge to move the legs. These data support the use of GEn in DA-exposed and DA-naive patients. Prior DA exposure had no significant effect on efficacy or tolerability of GEn (600 or 1200 mg) in this pooled analysis of adults with moderate-to-severe primary RLS. The most common treatment-emergent adverse events were dizziness and somnolence. Both GEn doses significantly improved the IRLS Rating Scale total score change from baseline and CGI-I response vs placebo, regardless of prior DA exposure. No significant differences in the odds of CGI-I response at week 12 between DA-naive vs DA-exposed patients in any treatment group were seen however, with placebo there was a nonsignificant trend toward fewer responders among DA-exposed (34.0%) vs DA-naive (44.3%) patients. Across treatment arms, no significant differences between DA-naive and DA-exposed subgroups in IRLS Rating Scale total score change from baseline at any visit were seen, except week 1 in the placebo group (−6.1 DA-naive vs −3.4 DA-exposed, P = .020). Within DA-naive/DA-exposed patients we investigated the co-primary end points from the pivotal trials: mean change from baseline to week 12 in International RLS (IRLS) Rating Scale total score and proportion of responders (“much”/“very much” improved) on the investigator-rated Clinical Global Impression–Improvement (CGI-I) scale. ![]() ![]() Patients with a history of augmentation were excluded. Details on prior treatment duration and dose were unavailable. Patients were identified as DA-naive or DA-exposed, based on prior treatment with ropinirole, pramipexole, rotigotine, or pergolide mesylate, and the dopamine precursor levodopa. Here we assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with moderate-to-severe primary RLS, with or without prior DA exposure. Dopamine agonists (DAs) are a first-line therapy for moderate-to-severe restless legs syndrome (RLS), but these treatments may lead to complications, such as augmentation and impulse control disorders, requiring switching to another therapeutic class.
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