[2] Sleep disruption may leave people with RLS sleepy during the day, with low energy, and irritable or depressed.

[2][4][13] A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers.

[15] Medications used to treat RLS include dopamine agonists like pramipexole and gabapentinoids (α2δ ligands) like gabapentin.

Subsequently, other descriptions of RLS were published, including by Theodor Wittmaack [de] (1861) (in relation to whom it is sometimes known as Wittmaack-Ekbom syndrome).

[18] In 1945, Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, restless legs: clinical study of hitherto overlooked disease.

The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.

[22] In a survey among members of the Restless Legs Syndrome Foundation, it was found that up to 45% of patients had their first symptoms before the age of 20 years.

[39] Research and brain autopsies have implicated both the dopaminergic system and iron insufficiency in the substantia nigra.

Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies.

[65] As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in the evening and at night, not be triggered by other medical or behavioral conditions, and should impair one's quality of life.

[11] There are less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes.

[12] If RLS is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene, regular exercise, and stopping smoking.

Evidence supports the use of dopamine agonists including pramipexole, ropinirole, rotigotine, cabergoline, and pergolide.

[76] However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease.

[78] Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day.

This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day.

In many cases, the longer dopamine agonists have been used, the higher the risk of augmentation and rebound as well as the severity of the symptoms.

A 2007 study indicated that dopamine agonists used in restless legs syndrome can lead to an increase in compulsive gambling.

[22]" Among the opioids and their suggested doses are tramadol, codeine, morphine, oxycodone, hydrocodone, methadone (all of which are schedule II), and buprenorphine (a schedule III partial opioid-receptor agonist with a lower risk of causing respiratory depression or dependence, compared with the full-agonist opioids.

[32][34] The only data publicly available on the use of buprenorphine in the treatment of RLS are two posters presented at the 2019 and 2023 Associated Professional Sleep Society’s meetings.

[87] Other treatments have also been explored, such as valproate, carbamazepine, perampanel, and dipyridamole, but are either not effective or have insufficient data to support their use.

[89] This is thought to be due to positive expectancy effects and conditioning, which activate dopamine and opioid pathways in the brain.

[89] More than half of the benefit of RLS medications such as pramipexole and gabapentin enacarbil appears to be due to the placebo component based on clinical trial data.

[92] Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep.

[93] RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome.

[104] Today, calling WED/RLS "Ekbom syndrome" is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity.

Some doctors express the view that the incidence of restless legs syndrome is exaggerated by manufacturers of drugs used to treat it.

[93] Further, GlaxoSmithKline (GSK) ran advertisements that, while not promoting off-license use of their drug (ropinirole) for treatment of RLS, did link to the Ekbom Support Group website.

[107] These questionnaires provide information about the severity and progress of the disease, as well as the person's quality of life and sleep.