Restless Legs Syndrome (RLS): Definition, Symptom, Cause, and Treatment

Restless Legs Syndrome (RLS) is a condition that causes an overwhelming urge to move the legs, especially during periods of rest or inactivity. RLS significantly disrupts sleep and quality of life,  affecting 5-10% of adults, as highlighted in the research “Benzodiazepines for Restless Legs Syndrome” published in the Cochrane Library by Carlos, Karla, et al. (2017), with a higher prevalence in women. Its symptoms include intense leg discomfort, disrupted sleep, and daytime fatigue, with over 80% of sufferers also experiencing periodic limb movements (PLMS) during sleep, further impairing rest ( American Academy of Sleep Medicine (2009).

The causes of RLS are complex, involving genetic predisposition, iron deficiency, and dopamine imbalance. As explored by Xiong, Lan, et al. (2010), approximately 40-90% of those affected have a first-degree relative with the condition, and reduced brain iron levels aggravate symptoms. Impaired dopamine signaling is also a substantial contributor, and conditions such as pregnancy and chronic diseases like diabetes and kidney disease escalate the hazard of developing RLS.

Diagnosis is primarily based on clinical evaluation, focusing on symptom patterns, particularly the worsening of symptoms during rest and at night. Treatments consist of lifestyle modifications, such as improving sleep hygiene and regular exercise, along with medications like dopaminergic agents, iron supplements, and benzodiazepines. For severe cases, physical therapies such as pneumatic compression and TENS are utilized.

What Is Restless Legs Syndrome (RLS)?

Restless Legs Syndrome is a neurological disorder that causes an irresistible, intense compulsion, to move the legs. This condition is classified as a sleep disorder because it habitually interferes with sleep, leading to daytime fatigue and decreased quality of life. 

RLS acts on approximately 7-10% of the general population, with a higher prevalence in women, as discussed by Innes, Kim E., et al.’s (2011) scientific review “Prevalence of restless legs syndrome in North American and Western European populations: A systematic review.” The study further states that RLS is 1.5 to 2 times more common in women than in men, possibly due to hormonal factors and pregnancy-related changes.

According to the American Academy of Sleep Medicine (2009), in the article “Pregnancy-related Hormonal Changes Linked To Increased Risk Of Restless Legs Syndrome,” women are 1.5 to two times more likely than men to develop RLS. Additionally, AASM argues that 80 to 90 percent of individuals with RLS have a movement condition, periodic limb movements (PLMs) during sleep, attributed to involuntary jerking or twitching of the feet or legs. These movements mess with evening rest and instigate intense urges to move the legs.

The prevalence of Restless Legs Syndrome (RLS) is estimated to be between 5% and 15% in adults, as advanced by the research “Benzodiazepines for Restless Legs Syndrome” published in the Cochrane Library by Carlos, Karla, et al. (2017). The incidence of Restless Legs Syndrome (RLS) ranges from 2.2% to 7.9% when considering the frequency or severity of symptoms. Nevertheless, if the diagnosis is predicated solely on clinical interviews and differential diagnosis, the prevalence drops to between 1.9% and 4.6%. Individuals with RLS suffer tired sensations and movement conditions that further weigh heavily on their quality of life.

What Are the Symptoms of Restless Legs Syndrome (RLS)?

The main symptoms of Restless Legs Syndrome are an intense urge to move the legs, uncomfortable sensations in the legs, and sleep disturbances. These symptoms worsen during rest or inactivity, especially in the evening or at night. The following are the most common symptoms of Restless Legs Syndrome (RLS) as provided by the Cleveland Clinic’s (2023) article “What is restless legs syndrome?” 

• Overwhelming Urge to Move the Legs: An overwhelming urge to move the legs is a powerful, irresistible need to move the legs, especially when resting. This is the principal symptom of Restless Legs Syndrome (RLS) as specified by the American Academy of Sleep Medicine (2009) article “Pregnancy-related Hormonal Changes Linked To Increased Risk Of Restless Legs Syndrome,” which states above 80% of RLS sufferers are afflicted by periodic limb movements (PLMs).
• Unpleasant Sensations: Unpleasant sensations are uncomfortable feelings in the legs, described as crawling, creeping, itching, pulling, aching, or throbbing. These sensations also extend to the arms, chest, or head.
• Symptoms Worsening in the Evening or Night: Symptoms worsening in the evening or night is a condition where RLS symptoms become more severe during these times, causing sleep disturbances.
• Periodic Limb Movements (PLM): Periodic limb movements (PLM) are involuntary jerking or twitchy legs during sleep. More than 80% of people with RLS experience this symptom as presented by the American Academy of Sleep Medicine (2009) article “Pregnancy-related Hormonal Changes Linked To Increased Risk Of Restless Legs Syndrome.”
• Difficulty Sitting Still: Difficulty sitting still is the challenge of remaining seated for long periods, such as during travel, due to the discomfort caused by RLS.
• Variability of Symptoms: Variability of symptoms is the wide range in how often and intensely RLS symptoms occur, with some people experiencing them occasionally and others daily.
• Associated Problems: Associated problems are secondary issues such as mood changes, daytime tiredness, difficulty concentrating, and even depression or anxiety due to the sleep disruption caused by RLS.

What Are the Causes of Restless Legs Syndrome (RLS)?

The main causes of Restless Legs Syndrome include genetic factors, iron deficiency, dopamine imbalance, and certain medical conditions. RLS has a strong genetic component, with studies indicating that 40-90% of individuals with RLS have at least one first-degree relative (biological parents, sibling, or child) with the ailment as discovered by Xiong, Lan, et al. (2010) in the “Family Study of Restless Legs Syndrome in Quebec, Canada Clinical Characterization of 671 Familial Cases.” The most common causes of Restless Legs Syndrome (RLS) are given below as explored by Sleep Foundation’s article by Dr. Wells, Audrey (2024) “Restless Legs Syndrome (RLS)- What it is, its causes and symptoms, and how it can be addressed to improve sleep”:

• Genetics: Genetics is the hereditary passing of traits from parents to offspring. RLS runs in families. A comprehensive study by Schormair, Barbara, et al. (2024), “Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology, and risk prediction,” published in Nature Genetics conducted meta-analyses of genome-wide association studies (GWAS) involving 116,647 cases and over 1.5 million controls. This research identified 161 risk loci for RLS, confirming known loci and adding 139 new ones, underpinning the genetic basis of RLS.
• Iron deficiency: Iron deficiency is a condition characterized by low levels of iron in the body, breeding various health issues. Low iron levels in the brain precipitate RLS symptoms. The research, “Iron and restless legs syndrome: Treatment, genetics and pathophysiology,” published in the journal Sleep Medicine by Connor, James R., et al. (2016), found that iron supplementation addressed symptoms in RLS patients with low ferritin levels.
• Lower Dopamine: Lower dopamine refers to diminished dopamine levels, a neurotransmitter involved in movement control. Dopamine, a neurotransmitter involved in movement control, plays a role in RLS. Research propounds that impaired dopamine signaling in the brain contributes to RLS symptoms. A study by Bugnicourt, Jean-Marc (2024), “Dopamine Agonists in the Treatment of Restless Legs Syndrome: Too Much of a Good Thing?” published in the Journal of Sleep Medicine discusses how patients with RLS show a marked response to dopaminergic agents, indicating a hypodopaminergic state in the brain. The findings suggest that impaired dopamine signaling contributes to RLS symptoms.
• Pregnancy: Pregnancy is carrying one or more embryos or fetuses within the uterus. RLS is recurrent during pregnancy and as per a systematic review by Mislu, Esuyawkal, et al. (2023) published in Frontiers in Medicine, “Prevalence and factors associated with restless legs syndrome among pregnant women in middle-income countries: a systematic review and meta-analysis,” presented the pooled prevalence of RLS among pregnant women in middle-income countries to be 13.82%.
• Chronic diseases: Chronic diseases are long-lasting medical conditions that require ongoing management. Certain medical conditions, such as kidney disease, diabetes, and Parkinson’s disease, are associated with an elevated risk of developing RLS. A comprehensive assessment, “Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review” by Sarfapour, Yasaman, et al. (2023) disclosed that the prevalence of RLS among chronic kidney disease patients varies between 15% and 30%, with certain studies indicating rates as high as 68% in individuals with end-stage renal disease (ESRD).
• Antidepressants: Antidepressants, while primarily used to treat depression, exert RLS symptoms. Some medications in this category inflate or alleviate RLS, depending on their effects on neurotransmitter systems.

How Is Restless Legs Syndrome Diagnosed?

Restless Legs Syndrome (RLS) is diagnosed through clinical evaluation, symptom assessment, and additional tests. The diagnostic process was derived from a workshop at the National Institutes of Health, where the International Restless Legs Syndrome Study Group (2003) established updated diagnostic criteria for restless legs syndrome, also known as Willis-Ekbom disease (RLS/WED). The most common diagnostic criteria for RLS are defined and discussed below as laid out by the International Restless Legs Syndrome Study Group (2003):

• Complete medical history: Complete medical history is the process of collecting comprehensive information about a patient’s past and present health status. Physicians gather information about symptoms, frequency, and their effect on daily life.
• Symptom Evaluation: Symptom evaluation is the systematic assessment of a patient’s symptoms to aid in diagnosis. Doctors use the diagnostic criteria established by the International Restless Legs Syndrome Study Group (2003), which comprise:
  1. An urge to move the legs, followed by uncomfortable sensations. Bozorg, Ali M. (2022) in the Medscape article, “Restless Legs Syndrome Clinical Presentation,” mentions PLMS as involuntary, forceful dorsiflexion of the foot lasting 0.5 to 5 seconds and occurring every 20 to 40 seconds throughout sleep.
  2. Symptoms that worsen during periods of rest or inactivity
  3. Relief from symptoms through movement
  4. Symptoms that worsen in the evening or at night
• Physical and Neurological Exams: Physical and neurological exams are clinical assessments utilized to evaluate a patient’s physical health and neurological function. These help rule out other conditions that cause similar symptoms.
• Lab tests: Lab tests are diagnostic procedures encompassing analyzing blood or other bodily fluids to detect underlying health issues. Blood tests are conducted to check iron levels and other causative factors.
• Sleep study: A sleep study, known as a polysomnogram, is a complete recording of the biophysiological changes during sleep. In some cases, a polysomnogram is recommended to assess sleep quality and detect periodic limb movements during sleep. Research consistently shows that 80-90% of RLS patients exhibit PLMS when assessed through polysomnography (sleep studies) as argued by Drakatos, Panagis, et al. (2021) in the research review “Periodic limb movements during sleep: a narrative review.”

What Are the Treatments of Restless Legs Syndrome?

The main treatments for Restless Legs Syndrome are lifestyle changes, medications, and physical therapies. The causes of RLS are genetic factors, iron deficiency, and underlying medical conditions such as chronic kidney disease and diabetes. The most common treatments for Restless Legs Syndrome are given below as indicated by the American Academy of Sleep Medicine (2009) in the article “Pregnancy-related Hormonal Changes Linked To Increased Risk Of Restless Legs Syndrome”:

Lifestyle Changes

Lifestyle changes are modifications to daily habits that tackle RLS symptoms for many patients through bolstering sleep hygiene, managing stress, leg massages, hot baths, and exercise. 

Improving sleep hygiene is the adoption of practices that promote healthy and restorative sleep, such as establishing a consistent sleep schedule and creating a comfortable sleep environment. By maintaining regular sleep patterns and an optimal sleep setting, individuals with Restless Legs Syndrome (RLS) minimize the frequency and severity of symptoms on the authority of Johns Hopkins Medicine’s (2024) What is RLS? . Consistent sleep routines help prevent the aggravation of RLS symptoms during rest periods.

Exercise is engaging in consistent physical activity like aerobic and resistance training exercises. Structured, moderate exercise has been shown to alleviate RLS symptoms by augmenting general muscle function and circulation as posited by Batool-Anwar, Salma, et al.’s (2016) study “Lifestyle Factors and Risk of Restless Legs Syndrome: Prospective Cohort Study,” stating that continued physical activity narrowed the ferocity of RLS symptoms by 20-30%. 

Leg massage is gently rubbing and kneading the legs, performed before bedtime. It alleviates RLS symptoms by boosting blood flow and shrinking muscle tension as noted by Harvard Health Publishing’s (2023) article “Restless legs syndrome.” Massage before sleep eases discomfort and lessens the pull to move the legs, stoking superior sleep quality.

 A hot bath entails immersing the body in warm water, usually before bedtime to relax muscles and relieve tension. The warmth from a hot bath soothes muscle discomfort and encourages relaxation, which brings down the sensations associated with RLS. This pre-bedtime routine discourages leg motion, hence greater sleep quality for those affected. A research team led by Haghayegh, Shahab, et al. (2019), a PhD candidate in the Department of Biomedical Engineering at The University of Texas at Austin, conducted a systematic probe and meta-analysis examining the relationship between bathing, water temperature, and sleep quality. Their study, titled “Before-bedtime passive body heating by warm shower or bath to improve sleep: A systematic review and meta-analysis,” investigated 5,322 studies and selected approximately a dozen with robust methodologies to draw their conclusions. The study was published in Sleep Medicine Reviews.

Their findings underscore that bathing one to two hours—preferably 90 minutes—before bedtime in water heated to 104 to 109°F (40 to 43°C) builds up sleep quality. This practice assists individuals fall asleep, on average, about 10 minutes faster than usual.

Medications

These are the medications used when lifestyle changes are insufficient to manage RLS symptoms, which are dopaminergic agents, iron supplements, alpha-2-delta ligands, and benzodiazepines as postulated by Winkelman, John W. et al.’s (2016) research paper “Practice guideline summary: Treatment of restless legs syndrome in adults.” 

Dopaminergic agents are medications that accelerate dopamine levels in the brain such as ropinirole and pramipexole. Pramipexole has proven very efficacious in treating Restless Legs Syndrome (RLS). In a “Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome” by Quilici, S., et al. (2008), after 12 weeks of treatment, patients experienced a considerable reduction in symptoms, with a decrease in their RLS score that averaged -5.45 points. This improvement suggests that pramipexole works better than another standard medication, ropinirole, in assuaging RLS symptoms.

Pramipexole was nearly three times more likely to show noticeable improvement on the Clinical Global Impression scale contrasted with a placebo, as observed in the above-mentioned study.

These drugs are prescribed as first-line treatments for moderate to severe RLS because they address the dopamine imbalance believed to create the condition. By enhancing dopamine activity, these medications lower the frequency and intensity of RLS symptoms by 70-80% as elaborated by Bugnicourt, Jean-Marc’s (2024) study, “Dopamine Agonists in the Treatment of Restless Legs Syndrome: Too Much of a Good Thing?”

Iron supplements are dietary products that elevate iron levels in individuals with iron deficiency. For patients with low iron levels, supplementation can convalesce RLS symptoms. Iron is crucial in dopamine production and function, as noted in the Cleveland Clinic’s (2023) article “What is restless legs syndrome?”

Alpha-2-delta ligands are medications like gabapentin and pregabalin that target nerve signals to eliminate pain and discomfort. Gabapentin and pregabalin are effective in palliating pain and discomfort associated with RLS. Studies such as “Pharmacologic Treatment of Restless Legs Syndrome” by Lv, Qing, et al. (2021) show that these medications support 50-70% of patients. These medications are potent, especially for patients experiencing pain-like symptoms associated with RLS. By modulating nerve activity, alpha-2-delta ligands handle the intensity of RLS symptoms and generate comfort.

Benzodiazepines are a class of medications deployed short-term to aid with sleep. The American Academy of Sleep Medicine’s guidelines state that benzodiazepines do not directly treat RLS symptoms; they are, however, somniferous to cope with anxiety and aid in relaxation. 

“Benzodiazepines for restless legs syndrome,” a study published in the Cochrane Libray by Carlos, Karla, et al. (2017), posts that “At any rate, the Guideline does state that clonazepam can be used as an adjunctive medication, and benzodiazepines, mostly clonazepam, have been used to reduce the symptoms of RLS for many years.” This indirectly benefits those with RLS by allowing better rest, though they are not a primary treatment for the syndrome itself.

Physical Treatments

Physical treatments are therapeutic interventions designed to assist in managing symptoms of Restless Legs Syndrome (RLS), which are pneumatic compression devices and transcutaneous electrical nerve stimulation (TENS).

Pneumatic compression devices are therapeutic tools that apply rhythmic pressure to the legs using inflatable cuffs or sleeves. The devices amplify blood flow and cut muscle tension, relieving RLS symptoms of discomfort and setting the pace for good sleep. In the study, “Sequential Compression Devices for Treatment of Restless Legs Syndrome,” Eliasson, Arn H. & Lettieri, Christopher J. (2007) reported that in an uncontrolled, prospective interventional trial using pneumatic compression devices, 3 out of 10 patients experienced complete resolution of their RLS symptoms, while the remaining 6 patients saw an improvement in symptoms after 1 to 3 months of therapy.

Transcutaneous Electrical Nerve Stimulation (TENS) is a treatment that uses low-voltage electrical currents to stimulate nerves through electrodes placed on the skin. The clinical research study, “Transcutaneous electrical nerve stimulation in the management of restless legs syndrome symptoms: A single-blind, parallel-group clinical study,” by Şanli, Zeynep, Selcan, et al. (2024) published in the Journal of Sleep Research, revealed that the use of TENS therapy combined with a low dose of pramipexole (0.25 mg daily) expressed major advancement in RLS severity scores and sleep quality compared to pramipexole monotherapy alone.

The stimulation modulates nerve activity to allay the sensations of discomfort associated with RLS, providing a non-invasive method to attenuate symptoms in some individuals. 

What Age Group Does Restless Legs Syndrome Affect?

Restless legs syndrome affects children aged 8-11, adolescents aged 12-17, and ages 10, 20, and 45 in adults. A population-based study, “Restless legs syndrome: prevalence and impact in children and adolescents–the Peds REST study” published in the journal Sleep Medicine by Picchietti, Daniel, et al. (2007) spotlights RLS being incident in approximately 1.9% of children aged 8-11 years, 2.0% of adolescents aged 12-17, and 25% of adults with RLS between the ages of 10 and 20. The early-onset form of RLS begins in childhood and the signs and symptoms worsen slowly over time. The late-onset form starts after age 45 and tends to progress more rapidly.

What Opioids Are Used for Restless Leg Syndrome?

Opioids used for Restless Leg Syndrome treatment are methadone, oxycodone formulations, hydrocodone, and tramadol. A randomized controlled trial, “Opioids for restless legs syndrome” by Osório de Oliveira, César, et al. (2016) demonstrated the efficacy of combining oxycodone and naloxone for treating refractory RLS patients. After 12 weeks of treatment, 42% of the oxycodone/naloxone group were symptom-free.

How Much Oxycodone for Restless Legs Syndrome (RLS)?

To know how much oxycodone for Restless Legs Syndrome to take, stick to the recommended starting maximum daily dose for an opioid-naïve patient which is 10 mg/5 mg of oxycodone hydrochloride/naloxone hydrochloride taken every 12-hour intervals. As referenced by Lv, Qing, et al. (2021) in the research paper “Pharmacologic Treatment of Restless Legs Syndrome,” a 12-week double-blind and 40-week open-label trial with 306 patients with severe RLS demonstrated that 5.0 mg oxycodone and 2.5 mg naloxone administered twice daily—up titrated to a maximum of 40 mg and 20 mg twice daily, respectively—proved effective in patients with severe RLS who did not respond to dopaminergic drugs. This dosing is aligned with the pain indication for managing severe RLS.

Can Sleep Disorder Cause Restless Leg Syndrome?

Yes, sleep disorders can cause Restless Legs Syndrome (RLS), the common sleep disorders being obstructive sleep apnea, periodic limb movement, and insomnia. Polysomnographic (PSG) studies, as deliberated about in the research paper “Effects of restless legs syndrome (RLS) on sleep” by Bogan, Richard K. (2006) have shown that patients with Restless Legs Syndrome (RLS) experience major sleep disruptions. On average, they had less total sleep time (326.3 minutes) compared to those without RLS (383.3 minutes), lower sleep efficiency (73.2% versus 86.6%), and more frequent awakenings (12.2 times versus 7.4 times). Moreover, they recounted lower sleep quality and effectiveness, as measured by the Pittsburgh Sleep Quality Index, relative to people without RLS.