Update on the management of restless legs syndrome: existing and emerging treatment options

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder, characterized by a circadian variation of symptoms involving an urge to move the limbs (usually the legs) as well as paresthesias. There is a primary (familial) and a secondary (acquired) form, which affects a wide variety of individuals, such as pregnant women, patients with end-stage renal disease, iron deficiency, rheumatic disease, and persons taking medications. The symptoms reflect a circadian fluctuation of dopamine in the substantia nigra. RLS patients have lower dopamine and iron levels in the substantia nigra and respond to both dopaminergic therapy and iron administration. Iron, as a cofactor of dopamine production and a regulator of the expression of dopamine type 2-receptor, has an important role in the RLS etiology. In the management of the disease, the first step is to investigate possible secondary causes and their treatment. Dopaminergic agents are considered as the first-line therapy for moderate to severe RLS. If dopaminergic drugs are contraindicated or not efficacious, or if symptoms are resistant and unremitting, gabapentin or other antiepileptic agents, benzodiazepines, or opioids can be used for RLS therapy. Undiagnosed, wrongly diagnosed, and untreated RLS is associated with a significant impairment of the quality of life.

Keywords: pathophysiology; quality of life.

Figure 1

Algorithm for the management of RLS. Source: Adapted from Silber et al. Notes: Dopamine agonists are the treatment choice in most patients. Low-potency opioids and gabapentin are valuable alternatives for the treatment of daily RLS, but dopamine agonists should be used if they are unsuccessful. Abbreviation: RLS, restless legs syndrome.