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

Restless Legs Syndrome (RLS)refers to a condition where individuals experience uncomfortable sensations in their legs, often accompanied by an uncontrollable urge to move them. This disorder intensifies during the evening or at night, making it difficult for individuals to rest, leading to feelings of tiredness and grogginess. Although it affects both genders, RLS is more commonly reported in women.

The symptoms of RLS vary from mild to severe and include an intense urge to move the legs accompanied by sensations that are temporarily relieved by movement, according to a study by Mansur A et al. 2023, “Castillo PR, Rocha Cabrero F, et al. Restless Legs Syndrome.” These symptoms worsen during periods of inactivity or rest, especially in the evening, and significantly disrupt sleep patterns, leading to chronic sleep deprivation.

The exact cause of Restless Legs Syndrome remains unclear, but it is believed to involve a combination of genetic and environmental factors. An imbalance of dopamine, a neurotransmitter responsible for controlling muscle movements, plays a significant role in the development of RLS, according to a study by Maggi G. et al. 2024, “Prevalence and clinical profile of patients with restless legs syndrome in Parkinson’s Disease: A meta-analysis.” Additionally, underlying health conditions such as iron deficiency, kidney disease, or pregnancy contribute to the onset of this disorder.

Diagnosing Restless Legs Syndrome is primarily based on the patient’s symptoms and medical history. Healthcare providers look for the four cardinal signs of RLS: an overwhelming urge to move the legs, symptom relief through movement, worsening symptoms at rest, and symptoms that are more severe in the evening or night, according to a book by Gossard, T.R., Trotti, L.M., Videnovic, A. et al. 2021, “Restless Legs Syndrome: Contemporary Diagnosis and Treatment.” Additional tests, such as blood work or sleep studies, are conducted to rule out other conditions and confirm the diagnosis.

Treatment for Restless Legs Syndrome aims to relieve symptoms and improve sleep quality. Management strategies include lifestyle changes, such as regular exercise and avoiding caffeine or alcohol, along with medications that target the underlying dopamine imbalance or address specific symptoms, as studied by Guo S, Huang J, Jiang H., et al. 2017, “Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management.” In cases where RLS is linked to another medical condition, treating the underlying issue helps alleviate the symptoms of RLS.

What Is Restless Legs Syndrome (RLS)?

Restless Legs Syndrome (RLS) is a neurological sleep disorder characterized by an intense urge to move the legs, accompanied by uncomfortable sensations such as itching, pulling, crawling, or throbbing. These symptoms occur during periods of rest or inactivity, especially in the evening or at night, leading to difficulty falling asleep and leaving individuals feeling tired and groggy during the day. 

From 52 articles across 23 countries, the global RLS prevalence in 2019 was estimated to be 7.12% among adults 20–79 years of age, equating to 356.07 million affected individuals, according to a study by Song P., 2024, “The global and regional prevalence of restless legs syndrome among adults: A systematic review and modeling analysis.”

RLS is more prevalent in women than men, possibly due to hormonal differences and iron metabolism, both of which play a role in this movement condition, according to a study by Seeman MV. et al. 2020, “Why Are Women Prone to Restless Legs Syndrome?” These sensations are triggered by disruptions in dopamine pathways, which are crucial for regulating movement and sensory responses.

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

The symptoms of Restless Legs Syndrome (RLS) include an intense urge to move the legs, uncomfortable sensations in the limbs, and disruptions to sleep. These symptoms primarily manifest during rest and significantly interfere with sleep quality, leading to daytime fatigue and reduced quality of life, according to a study by Mansur A et al. 2023, “Castillo PR, Rocha Cabrero F, et al. Restless Legs Syndrome.”

The most common symptoms of Restless Legs Syndrome (RLS) are given below:

• Intense Urge to Move the Legs: The intense urge to move the legs is the defining symptom of RLS, characterized by an overwhelming need to move the legs. This urge intensifies during periods of inactivity, particularly in the evening or at night. The movement temporarily relieves discomfort but disrupts sleep patterns, causing individuals to feel tired and groggy the next day. Triggers include prolonged sitting or lying down while alleviating factors include walking or stretching.
• Uncomfortable Sensations in the Limbs: The uncomfortable sensations in the lower limbs in RLS are described as itching, pulling, crawling, or throbbing that occurs deep within the legs and is usually bilateral. The discomfort is most severe in the evening or night and lasts for minutes to hours. These sensations are the primary reason for sleep disturbances in individuals with RLS, as they are relieved only by movement.
• Sleep Disruption: RLS is classified as a sleep disorder because its symptoms lead to significant interruptions in sleep. Individuals have difficulty falling asleep or staying asleep due to the persistent need to move their legs, according to Joseph N. et al. 2022, “Study on restless leg syndrome and its relationship with quality of sleep among the general population of Mangalore, India.” This leads to sleep deprivation, which causes daytime fatigue, irritability, and difficulty concentrating. Chronic sleep disruption from RLS contributes to long-term health issues like cardiovascular disease.
• Daytime Fatigue and Grogginess: Daytime fatigue is the lack of restful sleep caused by RLS, which results in extreme tiredness and grogginess during the day. This symptom significantly impacts daily functioning, leading to decreased productivity, mood disturbances, and a lower quality of life. The severity of fatigue correlates with the frequency and intensity of nighttime symptoms.

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

The causes of Restless Legs Syndrome (RLS) are primarily linked to neurological disorders, age and gender, disruptions in the brain’s dopamine system, and low levels of iron. 

RLS is believed to be a neurological disorder in which dysfunction in the brain’s dopamine system affects muscle movements, leading to characteristic symptoms, according to a study by Maggi G. et al. 2024, “Prevalence and clinical profile of patients with restless legs syndrome in Parkinson’s disease: A meta-analysis.” Low levels of iron, a crucial co-factor for dopamine production, are found in individuals with anemia, chronic kidney disease, or diabetes, making them more susceptible to RLS. 

Additionally, lifestyle factors such as pregnancy, alcohol, caffeine, and tobacco use trigger or worsen symptoms. Certain medications, including antidepressants, antipsychotics, antihistamines, and calcium channel blockers, have also been linked to RLS, according to a study by Bliwise DL, Zhang RH, and Kutner NG. et al. 2020, “Medications associated with restless legs syndrome: a case-control study in the US Renal Data System (USRDS).” Poor sleep habits contribute to the severity of the condition, and the prevalence of RLS increases with age, with women being more frequently affected than men.

How to Diagnose Restless Legs Syndrome (RLS)?

To diagnose Restless Legs Syndrome (RLS), a combination of symptom evaluation, complete medical history, and specific lab tests are required. To accurately diagnose RLS, doctors rely on evaluating the intensity and frequency of symptoms, such as the intense urge to move the legs, described as itching, pulling, or crawling sensations, according to a book by Gossard, T.R., Trotti, L.M., Videnovic, A. et al. 2021, “Restless Legs Syndrome: Contemporary Diagnosis and Treatment.” 

A thorough physical and neurological exam is essential to rule out other movement conditions. Additionally, lab tests, including those that assess iron levels, are critical since low iron aggravates RLS symptoms. In some cases, a sleep study is conducted to observe disruptions caused by RLS, particularly for patients who experience severe sleep disturbances.

• Symptom Evaluation: The presence of an intense urge to move the legs, usually accompanied by uncomfortable sensations, is assessed.
• Complete Medical History: A detailed history is taken to identify any underlying conditions, family history, or medications that might contribute to RLS.
• Physical and Neurological Exams: These exams are conducted to rule out other neurological disorders or conditions with similar symptoms.
• Lab Tests: Tests to measure iron levels and screen for conditions like anemia or chronic kidney disease are performed, according to a study by Connor JR, Patton SM, Oexle K, and Allen RP. et al. 2017, “Iron and restless legs syndrome: treatment, genetics, and pathophysiology.”
• Sleep Study: In cases with significant sleep disruption, a sleep study is used to assess how RLS affects sleep patterns.

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

The treatments of Restless Legs Syndrome (RLS) include lifestyle changes, medications, and addressing underlying conditions. Effective management of RLS involves a combination of these treatments, tailored to the individual’s symptoms and underlying causes, to reduce discomfort and improve sleep quality, as studied by Guo S, Huang J, Jiang H., et al. 2017, “Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management.”

The treatment options for RLS are as follows:

• Lifestyle Changes 
• Medications 
• Addressing Underlying Conditions 
• Behavioral Therapy

Lifestyle Changes

Lifestyle changes are adjustments in daily habits and routines that alleviate the symptoms of RLS. These changes help manage the condition by reducing triggers and promoting better sleep hygiene. The lifestyle changes to manage and treat RLS, according to a study by Vlasie A. et al. 2021, “Restless Legs Syndrome: An Overview of Pathophysiology, comorbidities and Therapeutic Approaches (Review),” are as follows:

• Improving Sleep Hygiene: Establishing a regular sleep schedule, ensuring a comfortable sleep environment, and avoiding stimulants like caffeine and alcohol before bed reduce RLS symptoms.
• Exercise: Regular physical activity, particularly moderate exercise like walking or yoga, alleviates the intensity of symptoms.
• Stress Management: Techniques such as meditation, deep breathing exercises, and relaxation therapies help reduce stress, a known trigger for RLS.

Medications

Medications for RLS involve using drugs to manage symptoms by targeting the neurological pathways involved in the condition. These treatments are helpful for RLS as they directly address the brain’s dopamine system, which plays a crucial role in muscle movements and sensations, according to a study by Amir A., Masterson R., et al. 2022, “Restless Leg Syndrome: Pathophysiology, Diagnostic Criteria, and Treatment.” The medications used to treat RLS are as follows:

• Dopaminergic Medications: These drugs, such as pramipexole and ropinirole, are used as the first line of treatment to enhance dopamine levels and relieve RLS symptoms.
• Anticonvulsants: Medications like gabapentin help reduce sensory disturbances and discomfort in the legs.
• Opioids: In severe cases, low-dose opioids are prescribed to alleviate intense pain and discomfort.
• Benzodiazepines: These are used to aid sleep, although they do not directly treat RLS symptoms.

Addressing Underlying Conditions

Addressing underlying conditions involves treating or managing health issues that contribute to triggering or worsening RLS symptoms. This approach is critical as it targets the root causes of RLS. The underlying conditions that need to be addressed to treat RLS, according to a study published in Mayo Clinic Proceedings by  Silber MH. et al. 2020, “The Management of Restless Legs Syndrome: An Updated Algorithm,” are as follows:

• Iron Supplementation: For patients with low iron levels, supplements help reduce RLS symptoms by improving the brain’s dopamine function.
• Managing Chronic Conditions: Controlling conditions such as diabetes or chronic kidney disease helps lessen the severity of RLS symptoms.
• Adjusting Medications: If medications like antidepressants, antipsychotics, or antihistamines are contributing to RLS, doctors recommend alternative treatments.

Behavioral Therapy

Behavioral therapy refers to psychotherapies that focus on changing behaviors and thought patterns that worsen RLS symptoms. These therapies are helpful for RLS as they address the psychological factors contributing to the disorder. The therapies required to manage RLS, according to a review by Gossard TR. et al. 2021, “ Restless Legs Syndrome: Contemporary Diagnosis and Treatment,” are as follows:

• Cognitive Behavioral Therapy (CBT): This type of psychotherapy helps patients manage stress and anxiety, which exacerbate RLS symptoms, by teaching relaxation techniques and healthy coping mechanisms.
• Biofeedback: Biofeedback is a technique that teaches patients to control physiological processes, such as muscle tension, which reduces RLS symptoms.
• Mindfulness-Based Stress Reduction (MBSR): This therapy combines mindfulness practices with stress management techniques to help patients better manage RLS-related discomfort.

What Opioids Are Used for Restless Leg Syndrome?

The opioids used for Restless Leg Syndrome include methadone, oxycodone formulation, hydrocodone, and tramadol. These opioids are known to treat severe cases of Restless Legs Syndrome (RLS) when other treatments have not been effective. Many participants in the Restless Legs Syndrome Registry report that these opioids effectively control their symptoms, particularly when dealing with intense discomfort that disrupts sleep, according to a study by Silber MH et al. 2018, “The Appropriate Use of Opioids in the Treatmentof RLS.” 

The commonly used opioids to treat RLS are as follows:

• Methadone: Methadone is a long-acting opioid that is prescribed for its efficacy in managing severe RLS symptoms, particularly in patients who do not respond well to other medications.
• Oxycodone Formulations: Extended-release oxycodone is a medicine that provides consistent relief over time. It helps patients with RLS maintain better sleep quality.
• Hydrocodone: Another opioid option, hydrocodone, is a drug that is known for its potent pain-relieving effects. Hydrocodone significantly reduces the sensations associated with RLS.
• Tramadol: Tramadol, a less potent opioid, has some serotonin and norepinephrine reuptake inhibition properties. It is commonly prescribed for RLS, particularly in cases where pain is a prominent symptom.

How Much Oxycodone for Restless Legs Syndrome (RLS)?

The recommended starting dose for RLS is around 5 mg of oxycodone/naloxone, with adjustments made as necessary, according to the National Institute for Health and Care Excellence (NICE) 2015, “Restless legs syndrome: Oxycodone/naloxone prolonged release.” The Summary of Product Characteristics (SPC) recommends that the usual starting dose of oxycodone/naloxone for Restless Legs Syndrome (RLS) should be carefully adjusted to the individual’s needs, typically beginning at a low dose. The medication is administered at 12-hour intervals to manage symptoms effectively, according to NICE.

It’s important to note that the maximum daily dose should not exceed the limits set for pain indication to avoid potential side effects and dependency risks. Careful monitoring is essential when using opioids like oxycodone/naloxone for RLS, given the potential for addiction and other complications.

Does Hydrocodone Help with Restless Leg Syndrome?

Yes, hydrocodone helps with Restless Legs Syndrome (RLS). Hydrocodone, an opioid, provides relief for RLS symptoms by addressing the intense urge to move the legs and alleviating associated sensations such as itching, crawling, and throbbing, according to a study by Silber MH. et al. 2017, “The Appropriate Use of Opioids in the Treatment of Refractory Restless Legs Syndrome.” Hydrocodone works by altering the brain’s response to these discomforting sensations, offering temporary symptom control for individuals who do not respond well to other treatments. However, its use should be closely monitored due to potential risks of addiction and side effects.

Can Tramadol Effectively Treat Restless Legs Syndrome (RLS)?

Yes, tramadol can effectively treat Restless Legs Syndrome (RLS). Tramadol, an opioid-like pain reliever, works by affecting the brain’s neurotransmitters, particularly serotonin and norepinephrine, which are involved in pain and muscle movements. Tramadol has an average rating of 8.8 out of 10 from a total of 123 reviews for the off-label treatment of Restless Legs Syndrome. 86% of reviewers reported a positive experience, while 7% reported a negative experience, according to a review by Drugs.com, “Tramadol for Restless Legs Syndrome User Reviews.” By modulating these neurotransmitters, tramadol helps reduce the uncomfortable sensations and the intense urge to move the legs that characterize RLS, providing relief for patients, especially when other treatments have not been effective.

How Long Do Restless Legs Last After Opioid Withdrawal?

Restless Legs Syndrome (RLS) symptoms persist for varying lengths of time after opioid discontinuation, lasting several weeks to months. The duration of RLS symptoms during opioid withdrawal is influenced by factors such as the duration of opioid use, the dosage, and individual patient differences. The majority of individuals with withdrawal-related RLS symptoms had remission of symptoms by 3 months after discharge from the program, according to a commentary by Winkelman JW et al. 2023, “Opioids and restless legs syndrome: a double-edged sword,” published in Journal of Clinical Sleep Medicine.

While acute symptoms subside within a few weeks, lingering sensations persist for several months as the body adjusts to the absence of opioids. The persistence of these symptoms underscores the challenges of managing RLS in patients undergoing opioid withdrawal.