Restless legs syndrome treatment - gabapentinoids or dopamine agonists?

Abstract

The pathogenesis of restless legs syndrome (RLS) is still poorly understood. Nevertheless, several medications are in clinical use, namely dopamine agonists (DA), gabapentinoids, opioids, and ferrum preparations, and their effectiveness has been confirmed in numerous clinical trials. In 2025 the American Academy of Sleep Medicine published new practice guidelines and changed the positioning of previously highly rated medications. The first-line treatment options with a "strong recommendation" are now gabapentinoids (gabapentin, gabapentin enacarbil, pregabalin) along with intravenous ferric carboxymaltose. Dopamine agonists previously classified at the same level have been moved to the category of "conditional against". This was based on the clinical data on the effectiveness of gabapentinoids but was not based on new clinical trials proving lower efficacy of DAs. In our opinion, this change is related to the potential side effects of DAs as augmentation and for impulse control disorder. Nevertheless, gabapentinoids are recommended in high doses vs. DAs, which are recommended in low doses. In older patients with co-morbidities in whom gabapentinoids are not well tolerated it results in relatively high rates of withdrawal. In this point of view paper, we present our personal views (supported by clinical data) on the need for both groups of medications in clinical practice because none of them is free of potential side effects and may still be useful.