Introduction: Gabapentin enacarbil is a new treatment for restless legs syndrome (RLS). It is a prodrug of the anticonvulsant gabapentin. However, unlike gabapentin, gabapentin enacarbil does not demonstrate saturable absorption. This allows for once-daily dosing and less variability in serum levels.
Areas covered: This review focuses on therapies used to treat RLS, both historical and recent. Data from available trials are summarized, with a particular focus on the efficacy and safety of gabapentin enacarbil. Potential advantages and disadvantages of this therapy in comparison with other RLS treatment modalities are discussed.
Expert opinion: Placebo-controlled trials of gabapentin enacarbil demonstrate considerable efficacy in the treatment of RLS. However, head-to-head trials comparing gabapentin enacarbil with other medications used in the treatment of RLS, including gabapentin, are lacking. Potential advantages with gabapentin enacarbil related to its pharmacokinetic profile are thus difficult to ascertain. Efficacy of gabapentin enacarbil appears comparable with that of the dopamine agonists, long considered the therapy of choice in patients with RLS. Given the lack of direct-comparison trials, and the significant cost differential of gabapentin enacarbil versus established therapies, the drug is likely to be used for patients who have failed other medication trials, or those who experience prolonged symptoms and prefer once-daily dosing.