Restless legs syndrome (RLS) is a common, sensorimotor, circadian sleep disorder characterized by the urge to move the legs, particularly at nighttime. It is important to differentiate primary and secondary RLS from other conditions, which can mimic the symptoms of RLS, in particular neuropathy and cramps. Despite considerable advances, the understanding of RLS pathophysiology remains incomplete. Many hypotheses focus on central nervous system structures, although there is increasing evidence that peripheral structures may also be important. There is insufficient evidence at the moment to recommend changes in lifestyle, nutritional supplements and any specific nonpharmacologic treatments. The first-line drugs continue to be dopaminergic medications, including pramipexole, ropinirole, rotigotine transdermal patch and levodopa. However, the phenomenon of RLS augmentation, a paradoxical worsening of symptoms by dopaminergic treatment remains as major problem in treatment of RLS, and prevention of augmentation is one of the main goals in the management of RLS. RLS requires treatment only if it has a significant impact on the patient's nighttime sleep or daily activities. Doses of dopamine agonists should be kept to the minimum required for acceptable symptom reduction. Augmentation may require treatment withdrawal, with prescription of alternate medication. Alternative or additional pharmacologic treatment with a lower level of overall quality of evidence includes opioids (codeine, tramadol, and oxycodone) and anticonvulsants (gabapentin, gabapentin enacarbil, and pregabalin). The choice of the medication should be based on the severity of RLS and the effectiveness of medication for the short-term or long-term treatment of RLS. Iron deficiency must be identified at diagnosis; treatment may improve RLS symptoms and potentially may lower risk of augmentation. There is no clear evidence for treatment of secondary RLS, but agents used in primary RLS should be tried. Comparative long-term trials are required to assess differences in efficacy and augmentation rates between medications used for treatment of RLS.
