Restless legs syndrome-current therapies and management of augmentation

Idiopathic restless legs syndrome (RLS) can severely affect quality of life and disturb sleep, so that pharmacological treatment is necessary, especially for elderly patients. Treatment guidelines recommend initiation of therapy with dopamine agonists (pramipexole, ropinirole or the rotigotine transdermal patch, all approved in most countries) or α-2-δ ligands (gabapentin enacarbil, approved in the USA and Japan), depending on the country and availability. Where approved, opioids (prolonged release oxycodone-naloxone, approved in Europe) are also recommended as a second-line therapy for severe RLS. Several iron formulations can be effective but are not yet approved for RLS therapy, whereas benzodiazepines and other anticonvulsants are not recommended or approved. Less is known about effective management of RLS that is associated with other conditions, such as uraemia or pregnancy. Furthermore, very little data are available on the management of RLS when first-line treatment fails or patients experience augmentation. In this Review, we summarize state-of-the-art therapies for RLS in the context of the diagnostic criteria and available guidelines, based on knowledge ranging from Class I evidence for the treatment of idiopathic RLS to Class IV evidence for the treatment of complications such as augmentation. We consider therapies, including combination therapies, that are used in clinical practice for long-term management of RLS, despite a lack of trials and approval, and highlight the need for practical long-term evaluation of current trials.