Restless leg syndrome (RLS) is a neurological disorder characterized by uncomfortable sensations in the legs and momentary relief upon movement. The sensations, which are commonly reported as electrical, prickling, burning, tingling, and itching, typically worsen at night, when individuals are more likely to rest. This can be incredibly disruptive to sleep quality, which is why RLS is also classified as a sleep disorder.
The condition is estimated to affect 10% of the U.S. population and, as you can see in Figure 1, is more prevalent in women than in men. It’s also more prevalent in individuals of western European descent than those of Asian descent. Researchers believe that there is a strong genetic basis to RLS, since individuals with a family history of RLS are also very likely to have the disorder. Genome-wide association studies have identified variants in six different genes linked to RLS. While much remains unknown, some of these genes have been linked to the development of neurons.
Despite this, much evidence suggests that dysfunctions in the basal ganglia and in dopamine-producing neurons play roles in the pathology of RLS. These areas are responsible for controlling smooth muscle, which is involved in controlling involuntary movements like those in the digestive tract. Dysfunctions in the brain regions that control these muscles can lead to disruptive involuntary movements. More evidence to support the role of dopamine dysfunction in RLS comes from individuals with Parkinson’s disease, a degenerative condition in which dopamine-producing cells in the brain die at a rapid rate. These individuals are also more likely to develop RLS.
In the past, the American Academy of Sleep Medicine has recommended dopamine agonists (drugs that activate specific dopamine receptors) as evidence-based treatments for RLS in its clinical practice guidelines. A 2011 Cochrane systematic review and meta-analysis of 38 randomized controlled trials found that dopamine-agonists were effective in reducing symptoms of restlessness in individuals with RLS, when compared to placebo. However, participants taking dopamine agonists also had an 82% higher chance of experiencing adverse events, which may make such treatments undesirable for some. Adverse effects such as worsening symptoms over the long term (called “augmentation”) and an increase in impulse control problems led the Restless Leg Syndrome Foundation to downgrade dopamine agonists to a second-line choice for therapy in 2021.